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Purpose: There are limited data on antiviral treatment utilization and its impact on long-term outcomes of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after hepatic resection. We aimed to determine the utilization and impact of antivirals in HBV- and HCV-related HCC., Methods: This cohort study included 1,906 participants (1,054 HBV-related HCC and 852 HCV-related HCC) from 12 international sites. All participants had HBV- or HCV-related HCC and underwent curative surgical resection. The primary outcome was the utilization of antiviral therapy, and the secondary outcome was long-term overall survival (OS)., Results: The mean (±standard deviation [SD]) age was 62.1 (±11.3) years, 74% were male, and 84% were Asian. A total of 47% of the total cohort received antiviral therapy during a mean (±SD) follow-up of 5.0 (±4.3) years. The overall antiviral utilization for participants with HBV-related HCC was 57% and declined over time, from 65% before 2010, to 60% from 2010 to 2015, to 47% beyond 2015, P < .0001. The overall utilization of antivirals for HCV-related HCC was 35% and increased over time, from 24% before 2015 to 74% from 2015 and beyond, P < .0001. The 10-year OS was lower in untreated participants for both HBV (58% v 61%) and HCV participants (38% v 82%; both P < .0001). On multivariable Cox regression analysis adjusted for relevant confounders, antiviral therapy initiated before or within 6 months of HCC diagnosis was independently associated with lower mortality in both HBV- (adjusted hazard ratio [aHR], 0.60 [95% CI, 0.43 to 0.83]; P = .002) and HCV-related HCC (aHR, 0.18 [95% CI, 0.11 to 0.31]; P < .0001)., Conclusion: Antiviral therapy is associated with long-term survival in people with HBV- or HCV-related HCC who undergo curative resection but is severely underutilized.

Background: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival., Aim: To evaluate the impact of HCV treatment on such disparities., Methods: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia., Results: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001)., Conclusion: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection., (© 2024 John Wiley & Sons Ltd.)

This study compared gut (fecal) microbiota profiles between pre-term and full-term infants, assuming that pre-term infants without feeding intolerance would have gut microbiota similar to those of full-term infants. A total of 13 pre-term infants (gestational age < 37 weeks, birthweight ≤ 2500 g) and 10 full-term infants were included. The pre-term infants were assigned to the feeding tolerance (FT) group (n = 7) if their daily intake exceeded 100 mL/kg/day at two weeks after birth, or the feeding intolerance (FI) group (n = 6). Microbial DNA from weekly fecal samples was analyzed. The microbiota profiles of the pre-term infants and full-term infants were significantly different ( p = 0.0001), as well as the FT and FI groups ( p = 0.0009). The full-term group had more diversity, with higher concentrations of facultative anaerobes such as Bifidobacteriaceae and Lactobacteriaceae. The FT group's gut microbiota matured over four weeks, with higher levels of digestion-related bacteria, while the FI group had more pathogens. In the FI group, a significant difference was observed between the first and second weeks, with no significant differences noted between the first week and the third or fourth weeks. The delay in the development of the pre-term infants' gut microbiota may be associated with the FI.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na + /K + -ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder., (© 2024. The Author(s).)

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 ( p < 0.0001), 2.11 ( p = 0.0007), and 1.02 ( p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

The subject in this study was a female professional painter who underwent bilateral mastectomy because of bilateral breast cancer, experienced postoperative wound scarring, and developed alopecia due to the side effects of chemotherapy, which caused the patient to lose body image confidence and the motivation to engage in artistic creativity. The patient had shed tears early in the intervention and complained of difficulties with body image adjustment due to her altered appearance. Mastectomy patients must not only undergo drug treatment but also adjust psychologically to body image changes to decrease negative emotions. This was the author's motivation for involvement in this case. The nursing period was from 23 September to 30 December 2021. Physical, mental, spiritual, social, and family data were collected using observations and interviews. These data were evaluated and the main problems were determined to be disturbed body image related to altered body perception post-surgery, alopecia caused by chemotherapy, impaired physical mobility due to upper limb mobility limitations post-surgery, and nausea due to chemotherapy. The patient was encouraged to paint again and to use artistic creativity to comfort herself. Moreover, she was guided to express her innermost thoughts to face the impact of her changes in appearance. In addition, a care consultation channel was provided to facilitate experience sharing with other breast cancer patients, thus assisting the patient to cope with the mental impact of her treatments and face subsequent cancer treatments with a more positive attitude. Art therapy embraces a diverse variety of methods, including drawing and music. Art therapy is a valuable tool that facilitates both physical and mental healing. Based on this experience, nurses should include patients' close relatives when performing art therapy to facilitate shared care to overcome difficulties. We hope this nursing experience provides a practical reference for nurses.

Background: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective., Hypothesis: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope., Methods: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured., Results: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope., Conclusions: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Purpose: To develop a model-based deep neural network for high-quality image reconstruction of undersampled multi-coil CEST data., Theory and Methods: Inspired by the variational network (VN), the CEST image reconstruction equation is unrolled into a deep neural network (CEST-VN) with a k-space data-sharing block that takes advantage of the inherent redundancy in adjacent CEST frames and 3D spatial-frequential convolution kernels that exploit correlations in the x-ω domain. Additionally, a new pipeline based on multiple-pool Bloch-McConnell simulations is devised to synthesize multi-coil CEST data from publicly available anatomical MRI data. The proposed network is trained on simulated data with a CEST-specific loss function that jointly measures the structural and CEST contrast. The performance of CEST-VN was evaluated on four healthy volunteers and five brain tumor patients using retrospectively or prospectively undersampled data with various acceleration factors, and then compared with other conventional and state-of-the-art reconstruction methods., Results: The proposed CEST-VN method generated high-quality CEST source images and amide proton transfer-weighted maps in healthy and brain tumor subjects, consistently outperforming GRAPPA, blind compressed sensing, and the original VN. With the acceleration factors increasing from 3 to 6, CEST-VN with the same hyperparameters yielded similar and accurate reconstruction without apparent loss of details or increase of artifacts. The ablation studies confirmed the effectiveness of the CEST-specific loss function and data-sharing block used., Conclusions: The proposed CEST-VN method can offer high-quality CEST source images and amide proton transfer-weighted maps from highly undersampled multi-coil data by integrating the deep learning prior and multi-coil sensitivity encoding model., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background & Purpose: Oral health education helps older adults optimize their oral health. However, traditional lecture-based oral health education has limitations, exacerbated by the COVID-19 pandemic. Mobile augmented reality (MAR) has emerged as an alternative educational method. This study compared the effectiveness of MAR-integrated oral health education with that of lecture-based education and no education., Methods: This parallel, randomized controlled, open-label trial enrolled 75 older adults from six activity centers. The participants were randomly assigned, by a random number table technique, to the lecture-based, MAR, or control group. Data on oral healthcare-related knowledge, self-efficacy, and oral health status were collected through questionnaires and oral examinations at baseline, immediately after the intervention, and at a 2-week follow-up. The MAR system's usability was assessed. Statistical analyses, comprising descriptive statistics and inferential tests, were performed., Results: Data from 61 participants were analyzed, 22 in the lecture-based group, 20 in the MAR group, and 19 in the control group. Both lectures and MAR education significantly improved oral health status. However, changes in knowledge and self-efficacy scores were significantly different only for the MAR versus control group (p = .002 and .001, respectively). The MAR group demonstrated better knowledge and self-efficacy retention than did the lecture-based group, without significant difference. Usability assessment revealed potential for improvement in the MAR system., Conclusions: MAR-integrated oral health education enhanced the knowledge, self-efficacy, and oral health status of community-dwelling older adults. However, addressing technology adoption and usability challenges is vital. Longer-term evaluations and broader geographical studies are recommended., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Fungal sulfated polysaccharides (SPS) have been used in the pharmaceutical industry. In this study, sodium sulfate was employed as an elicitor to induce stress on the mycelia of Antrodia cinnamomea for the biosynthesis of SPS with high sulfate content. Sodium sulfate treatments increased the yield of SPS to 4.46 % and increased the sulfate content to 6.8 mmol/g of SPS. SPS were extracted from A. cinnamomea cultured with 500 mM sodium sulfate; these SPSs are denoted as Na500. Na500 exhibited the highest sulfate content and dose-dependent inhibitory activity against LPS-induced production of macrophage interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β). Mechanistically, Na500 hindered the phosphorylation of transforming growth factor-β receptor II (TGFRII), extracellular signal-regulated kinases (ERK), and protein kinase B (AKT) expression. A purified 7.79 kDa galactoglucan, Na500 F3, augmented the anti-inflammation activity by inhibiting LPS-induced TGFβ release. Additionally, Na500 F3 restrained the LPS-induced phosphorylation of p-38, ERK, AKT, and TGFRII in RAW264.7 cells. Na500 F3 impeded the proliferation of lung cancer H1975 cells by inhibiting the phosphorylation of focal adhesion kinase, ERK, and Slug. The anti-inflammation and anticancer properties of Antrodia SPS contribute to its health benefits, suggesting its utility in functional foods., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Marriage has long been considered protective against suicide, but shifting social norms since 2000 in Hong Kong raise doubts regarding whether this is still the case. The aim of the study was to investigate the changing association between suicide and marital status., Methods: Official suicide data for 2002-2020 in Hong Kong were obtained. Suicide rates and suicide risk ratios were calculated by gender, age group, and marital status (married, never-married, widowed, divorced/separated)., Results: Suicide risk decreased significantly over time for men and women of all ages. People who were never-married, divorced/separated, had significantly higher suicide risks than their married counterparts. Increasing suicide risks over time were observed for never-married men aged 20-49 years, never-married women aged 35-49 years, and divorced/separated men aged 20-34 years. Widowed men and women of any age had higher suicide risks compared with previous studies in Hong Kong., Limitations: Marital status is a time-varying covariate, and the time spent in a given marital status could affect suicide risk. Some age and gender subgroups had much smaller sample sizes than others, thus it is possible that our suicide risk estimates were overestimated., Conclusions: Despite rapidly social changing in Hong Kong during the study period, marriage remains a strong protective factor against suicide for men and women. The protective effect is particularly evident for younger people. Increasing suicide rates for divorced/separated, never-married, or widowed people suggest that they require more psychosocial support., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Sentiment analysis is a significant yet difficult task in natural language processing. The linguistic peculiarities of Cantonese, including its high similarity with Standard Chinese, its grammatical and lexical uniqueness, and its colloquialism and multilingualism, make it different from other languages and pose additional challenges to sentiment analysis. Recent advances in models such as ChatGPT offer potential viable solutions., Objective: This study investigated the efficacy of GPT-3.5 and GPT-4 in Cantonese sentiment analysis in the context of web-based counseling and compared their performance with other mainstream methods, including lexicon-based methods and machine learning approaches., Methods: We analyzed transcripts from a web-based, text-based counseling service in Hong Kong, including a total of 131 individual counseling sessions and 6169 messages between counselors and help-seekers. First, a codebook was developed for human annotation. A simple prompt ("Is the sentiment of this Cantonese text positive, neutral, or negative? Respond with the sentiment label only.") was then given to GPT-3.5 and GPT-4 to label each message's sentiment. GPT-3.5 and GPT-4's performance was compared with a lexicon-based method and 3 state-of-the-art models, including linear regression, support vector machines, and long short-term memory neural networks., Results: Our findings revealed ChatGPT's remarkable accuracy in sentiment classification, with GPT-3.5 and GPT-4, respectively, achieving 92.1% (5682/6169) and 95.3% (5880/6169) accuracy in identifying positive, neutral, and negative sentiment, thereby outperforming the traditional lexicon-based method, which had an accuracy of 37.2% (2295/6169), and the 3 machine learning models, which had accuracies ranging from 66% (4072/6169) to 70.9% (4374/6169)., Conclusions: Among many text analysis techniques, ChatGPT demonstrates superior accuracy and emerges as a promising tool for Cantonese sentiment analysis. This study also highlights ChatGPT's applicability in real-world scenarios, such as monitoring the quality of text-based counseling services and detecting message-level sentiments in vivo. The insights derived from this study pave the way for further exploration into the capabilities of ChatGPT in the context of underresourced languages and specialized domains like psychotherapy and natural language processing., (©Ziru Fu, Yu Cheng Hsu, Christian S Chan, Chaak Ming Lau, Joyce Liu, Paul Siu Fai Yip. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.01.2024.)

Ultrafast excited-state dynamics of the simplest nitrostilbenes, namely trans -4-nitrostilbene ( t -NSB), was studied in solvents of various polarities with ultrafast broadband time-resolved fluorescence and transient absorption spectroscopies, and by quantum-chemical computations. The results revealed that the initially excited S 1 (ππ*) state deactivation dynamics is strongly influenced by the solvent polarity. Specifically, the t -NSB S 1 -state lifetime decreases by three orders of magnitude from ∼60 ps in high-polarity solvents to ∼60 fs in nonpolar solvents. The strong solvent-polarity dependence arises from the differences in dipole moments among the S 1 and relevant states, including the major intersystem crossing (ISC) receiver triplet states, and therefore, the solvent polarity can modulate their relative energies and ISC rates. In nonpolar solvents, the sub-100 fs lifetime is due to a combination of efficient ISC and internal conversion. In medium-polarity solvents, the S 1 -state population decays via a competing ISC relaxation mechanism in a biphasic manner, and the ISC rates are found to obey the inverse energy gap law of the strong coupling case. In high-polarity solvents, the S 1 state is stabilized to a much lower energy such that ISC becomes energetically infeasible, and the S 1 state decays via barrier crossing along the torsion angle of the central ethylenic bond to the nonfluorescent perpendicular configuration. Regardless of the initial S 1 -state deactivation pathways in various solvents, the excited-state population is ultimately trapped in the metastable T 1 -state perpendicular configuration, at which a slower ISC occurs to bring the system to the ground state and bifurcate into either trans or cis form of NSB.

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially crossover helix ends is elucidated. This structural model aligns well with scanning tunneling microscopy (STM) imaging. The present work enhances the precision of nanoscale organic synthesis, offering prospects for controlled ligand positioning on scaffolds. This advancement paves the way for further applications in nanomedicine through selective protein interaction, manipulation of cell surface receptor functions, and developments of more complex polyproline-based nanostructures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The progressive cognitive decline, an integral component of Alzheimer's disease (AD), unfolds in tandem with the natural aging process. Neuroimaging features have demonstrated the capacity to distinguish cognitive decline changes stemming from typical brain aging and AD between different chronological points., Objective: To disentangle the normal aging effect from the AD-related accelerated cognitive decline and unravel its genetic components using a neuroimaging-based deep learning approach., Methods: We developed a deep-learning framework based on a dual-loss Siamese ResNet network to extract fine-grained information from the longitudinal structural magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We then conducted genome-wide association studies (GWAS) and post-GWAS analyses to reveal the genetic basis of AD-related accelerated cognitive decline., Results: We used our model to process data from 1,313 individuals, training it on 414 cognitively normal people and predicting cognitive assessment for all participants. In our analysis of accelerated cognitive decline GWAS, we identified two genome-wide significant loci: APOE locus (chromosome 19 p13.32) and rs144614292 (chromosome 11 p15.1). Variant rs144614292 (G > T) has not been reported in previous AD GWA studies. It is within the intronic region of NELL1, which is expressed in neurons and plays a role in controlling cell growth and differentiation. The cell-type-specific enrichment analysis and functional enrichment of GWAS signals highlighted the microglia and immune-response pathways., Conclusions: Our deep learning model effectively extracted relevant neuroimaging features and predicted individual cognitive decline. We reported a novel variant (rs144614292) within the NELL1 gene.

Background: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor., Objective: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation., Methods: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation., Results: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC)., Conclusions: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

Background: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective., Methods: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan's Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease., Results: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth., Conclusion: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited., Aims: To assess the treatment and renal/bone safety outcomes following the switch to TAF., Methods: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF., Results: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m 2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019)., Conclusions: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable., (© 2023 John Wiley & Sons Ltd.)

Purpose: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap., Methods: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched., Results: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively., Conclusion: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR)., Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR., Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81)., Conclusion: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Background: The effect of cholinesterase inhibitor (ChEI) on mild cognitive impairment (MCI) is controversial. Brain age has been shown to predict Alzheimer's disease conversion from MCI., Objective: The study aimed to show that brain age is related to cognitive outcomes of ChEI treatment in MCI., Methods: Brain MRI, the Clinical Dementia Rating (CDR) and Mini-Mental State Exam (MMSE) scores were retrospectively retrieved from a ChEI treatment database. Patients who presented baseline CDR of 0.5 and received ChEI treatment for at least 2 years were selected. Patients with stationary or improved cognition as verified by the CDR and MMSE were categorized to the ChEI-responsive group, and those with worsened cognition were assigned to the ChEI-unresponsive group. A gray matter brain age model was built with a machine learning algorithm by training T1-weighted MRI data of 362 healthy participants. The model was applied to each patient to compute predicted age difference (PAD), i.e. the difference between brain age and chronological age. The PADs were compared between the two groups., Results: 58 patients were found to fit the ChEI-responsive criteria in the patient data, and 58 matched patients that fit the ChEI-unresponsive criteria were compared. ChEI-unresponsive patients showed significantly larger PAD than ChEI-responsive patients (8.44±8.78 years versus 3.87±9.02 years, p = 0.0067)., Conclusions: Gray matter brain age is associated with cognitive outcomes after 2 years of ChEI treatment in patients with the CDR of 0.5. It might facilitate the clinical trials of novel therapeutics for MCI.

Background: Conventional epidurography (CE) is thought to have insufficient usefulness on percutaneous epidural adhesiolysis (PEA). We aimed to evaluate the association between the outcome of PEA and cone-beam computed tomography-reformatted epidurography (CBCT-RE)., Methods: After ethics board approval and written informed consent were obtained, we performed 30 PEA in 26 participants, and evaluated their post-PEA image findings. Two independent radiologists categorized and recorded the occurrence of contrast in the intracanal ventral and extraforaminal regions on CE, and in the dorsal canal (DC), ventral canal (VC), dorsal foramen (DF), and ventral foramen (VF) on CBCT-RE. Reproducibility was assessed using intraclass correlation coefficients (ICCs). Baseline characteristics along with contrast distribution patterns of CE and CBCT-RE were analyzed in terms of their association with symptom relief at 1 month after PEA., Results: The rate of patients with symptoms relief >50% after PEA was 63.3%. The inter-reader agreement was higher for CBCT-RE (ICC = 0.955) than for CE (ICC = 0.793). Participants with contrast coexisting in VC and DF adjacent to the irritated nerve root on CBCT-RE ( p = 0.015) had a significantly better response after PEA than those without contrast at these locations on CBCT-RE, independent of baseline characteristics (adjusted odds ratio: 11.414 [ p = 0.012])., Conclusion: CBCT-RE with identifying contrast distribution patterns is useful for predicting outcome of PEA., 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.)

This study compares the bioactivity of six sulfated polysaccharides derived from glucose- and sucrose-feeding extracted from P. cocos. Anti-inflammatory potentials of these polysaccharides were evaluated by pretreating lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Of the tested polysaccharides, the sulfated polysaccharide derived from sucrose-feeding at the concentration of 40 g/l (referred to as "suc 40") exhibited the highest anti-inflammatory activity, of 83 %, and 33 % inhibition of IL-6 and TNF-α secretion, respetively. It achieved this by inhibiting the p-38 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways. On the other hand, the sulfated polysaccharide derived from glucose-feeding at a concentration of 20 g/l (referred to as "glc 20") demonstrated the greatest anti-lung cancer activity. This was achieved by inducing apoptotic-related molecules, such as poly (ADP-ribose) polymerase (PARP) and CHOP. Furthermore, glc 20 had the highest contents of sulfate, fucose, and mannose compared to the other tested polysaccharides. This suggests that the composition of monosaccharide residues are critical factors influencing the anti-inflammatory and anti-cancer activities of these sulfated polysaccharides. Overall, this study highlights the potential of sulfated polysaccharides derived from P. cocos to function as bioactive compounds with anti-inflammatory and anti-cancer properties., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bifidobacterium longum subsp. infantis BLI-02, Lactobacillus paracasei ET-66, Lactobacillus plantarum LPL28, and Lactobacillus acidophilus TYCA06, isolated from healthy breast milk, miso, and the healthy human gut, were assessed for safety in this study. BLI-02, LPL28, TYCA06, and ET-66 exhibited no antibiotic resistance and mutagenic activity in the Ames test at the highest dosage (5000 μg/plate). No genotoxicity was observed in micronucleus and chromosomal aberration assays in rodent spermatogonia at the maximum dosage of 10 g/kg body weight (BW). No acute and sub-chronic toxicity occurred in mice and rats at the maximum tested dosage of 10 g/kg BW and 1.5 g/kg BW, respectively. The lyophilized powder of these strains survived a low pH and high bile salt environment, adhering strongly to Caco-2 cells. Unique antimicrobial activities were noted in these strains, with BLI-02 demonstrating the best growth inhibition against Vibrio parahaemolyticus , LPL28 exhibiting the best growth inhibition against Helicobacter pylori , and ET-66 showing the best growth inhibition against Aggregatibacter actinomycetemcomitans . Based on the present study, the lyophilized powder of these four strains appears to be a safe probiotic supplement at tested dosages. It should be applicable for clinical or healthcare applications.

The role of neurotrophic factors, oxidative stress, and inflammation in the pathogenesis of Alzheimer's disease (AD) has been explored. Animal studies have reported the positive effects of probiotics on these factors. Some clinical studies also support the potential role of probiotics in improving cognitive function via the gut-brain axis in older adults. However, clinical experimental studies evaluating the efficacy of probiotics targeting the neurotrophic factors and inflammatory biomarkers, particularly among AD patients, remain very limited. In this randomized, double-blinded, active-controlled trial, we used multi-strain probiotic supplements, including Bifidobacterium longum subsp. infantis BLI-02, B. breve Bv-889, B. animalis subsp. lactis CP-9, B. bifidum VDD088, and Lactobacillus plantarum PL-02 as the intervention. Participants were divided into an active control group (received probiotic supplements containing 5 × 10 7 colony-forming units per day, CFU/day) and a treatment group (1 × 10 10 CFU/day). Student's t test was applied as the main method of statistical analysis. After 12 weeks of intervention, the treatment group demonstrated a 36% increase in serum brain-derived neurotrophic factor (BDNF) (* p = 0.005), a reduction in IL-1β (* p = 0.041), and an increase in antioxidant superoxide dismutase (SOD) (* p = 0.012). No significant change was found in the active control group. A trend toward less cognitive deterioration was observed, but not statistically significant. In conclusion, this study presents evidence supporting the benefits of multi-strain probiotics in enhancing BDNF, ameliorating inflammation and oxidative stress in AD patients.

Counting the repetition of human exercise and physical rehabilitation is common in rehabilitation and exercise training. The existing vision-based repetition counting methods less emphasize the concurrent motions in the same video, and counting skeleton in different view angles. This work analyzed the spectrogram of the pose estimation cosine similarity to count the repetition. Besides the public datasets. This work also collected exercise videos from 11 adults to verify that the proposed method can handle concurrent motion and different view angles. The presented method was validated on the University of Idaho Physical Rehabilitation Movements Data Set (UI-PRMD) and MM-fit dataset. The overall mean absolute error (MAE) for MM-fit was 0.06 with off-by-one Accuracy (OBOA) of 0.94. As for the UI-PRMD dataset, MAE was 0.06 with OBOA 0.95. We have also tested the performance in various camera locations and concurrent motions with 57 skeleton time-series videos with an overall MAE of 0.07 and OBOA of 0.91. The proposed method provides a view-angle and motion agnostic concurrent motion counting. This method can potentially use in large-scale remote rehabilitation and exercise training with only one camera., Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00258-3., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Measuring lipid composition provides more information than just total lipid content. Hence, the non-invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J-difference editing of unsaturated lipid resonances., Methods: The TE dependence of J-difference-edited (JDE) MRS was verified in the density-matrix simulation, soybean oil phantom, in-vivo experiments of white adipose tissue (WAT), and skeletal muscles using single-voxel MEGA-PRESS sequence at 3T. The peak SNRs and Cramér-Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7)., Results: The optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools., Conclusion: The JDE-MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: This study aimed to evaluate the efficacy and reliability of three-dimensional (3D) fusion guidance in roadmapping for fluoroscopic navigation during trans-arterial embolization for refractory musculoskeletal pain (TAE-MSK pain) in the extremities., Methods: The included research patients were divided into two groups: group A-TAE-MSK pain performed without the use of 3D fusion guidance; group B-TAE-MSK pain performed with the use of 3D fusion guidance for fluoroscopic navigation. We compared the procedure time, radiation dose, visual analogue scale for pain scores, and adverse effects (before and 3 months after TAE-MSK pain) among the two groups. In the group B, we determined the reliability of ideal branch angle for pre-operative non-contrast 3D magnetic resonance angiography (MRA) and intra-operative 3D cone beam computed tomography (CBCT) angiography., Results: We recruited 65 patients, including 23 males and 42 females (average age 58.20±12.58 years), with 38 and 27 patients in groups A and B. A total of 247 vessels were defined as target branch vessels. Significant changes were observed in the fluoroscopy time which was 32.31±12.39 and 14.33±3.06 minutes, in group A and group B (P<0.001), respectively; procedure time, which was 46.45±17.06 in group A and 24.67±9.78 in group B (P<0.001); and radiation exposure dose, determined as 0.71±0.64 and 0.34±0.29 mSv (P<0.01) in group A and group B, respectively. Furthermore, the number of target branch vessels, that underwent successful catheterization were 107 (97%) in group B as compared to 96 (70%) in group A, which was also significant (P<0.001). The study also showed that the ideal branch-angle has a similarly high consistency in pre-operative and intra-operative angiography based on the intra-class correlation coefficient (ICC) (0.994; 0.990, respectively)., Conclusions: 3D fusion guidance for fluoroscopic navigation not only is a reliable process, but also effectively reduces the operation time and radiation dose of TAE-MSK pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-490/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Cellular retinoic acid binding protein 1 (CRABP1) participates in the regulation of retinoid signaling. Previous studies showed conflicting results regarding the role of CRABP1 in tumor biology, including protumorigenic and tumor-suppressive effects in different types of cancer. Our bioinformatics analyses suggested that CRABP1 expression was downregulated in thyroid cancer. Ectopic expression of CRABP1 in thyroid cancer cells suppressed migratory and invasive activity without affecting cell growth or cell cycle distribution. In transformed normal thyroid follicular epithelial cells, silencing of CRABP1 expression increased invasiveness. Additionally, CRABP1 overexpression was associated with downregulation of the mesenchymal phenotype. Kinase phosphorylation profiling indicated that CRABP1 overexpression was accompanied by a decrease in phosphorylation of epidermal growth factor (EGF) receptor and downstream phosphorylation of Akt, STAT3, and FAK, which were reversed by exogenous EGF treatment. Immunohistochemical analysis of our tissue microarrays revealed an inverse association between CRABP1 expression and disease stage of differentiated thyroid cancer. Taken together, our results suggest that CRABP1 expression is aberrantly lost in thyroid cancer, and this downregulation promotes the epithelial-mesenchymal transition at least partly through modulating EGF receptor signaling., (© 2023 Wiley Periodicals LLC.)

The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid., 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 B.V. All rights reserved.)

Background: Elderly patients with intra-abdominal infection are more vulnerable to sepsis progression, especially in those who had concomitant bacteremia. The time to positivity (TTP) of blood cultures in patients with bacteremia is considered to be a prognostic factor for some bacterial species. This study aimed to investigate the prognostic value of TTP in elderly patients with intra-abdominal infection and Klebsiella pneumoniae bacteremia., Methods: A retrospective observational, case-control study was conducted at a single tertiary referral medical center. All elderly (aged ≥ 65 years) patients diagnosed with intra-abdominal infection and Klebsiella pneumoniae bacteremia in the emergency department between July 1, 2016, and June 30, 2021 were enrolled. The baseline characteristics, TTP of blood cultures, management strategy, and outcomes of each eligible patient were recorded and analyzed. The primary outcome was to examine the association between TTP and the 30-day mortality risk in enrolled patients., Results: A total of 101 patients were included in the study. The overall 30-day mortality rate was 11.9% (12/101). The median TTP of Klebsiella pneumoniae in the eligible patients was 12.5 (11-16) hours. There was a stepwise significantly decreased mortality rate as TTP increased ( p = 0.04). The TTP had a moderate mortality discrimination ability (area under receiver operating characteristic curve = 0.75, 95% CI = 0.65-0.83, p < 0.01). Furthermore, the Pittsburg bacteremia score (hazard ratio [HR] = 2.19, p < 0.01) and TTP (HR = 0.82, p = 0.04) were identified as independent factors associated with 30-day mortality., Conclusions: TTP was associated with 30-day mortality risk in elderly patients with Klebsiella pneumoniae bacteremia and intra-abdominal infection. Clinicians can utilize TTP for risk stratification, and initiate prompt treatment in those patients with shorter TTP., (Copyright © 2023 by Taiwan Society of Emergency Medicine & Ainosco Press. All Rights Reserved.)

Background: Water exchange across blood-brain barrier (BBB) (WEX BBB ) is an emerging biomarker of BBB dysfunction with potential applications in many brain diseases. Several MRI methods have been proposed to measure WEX BBB , but evidence remains scarce whether different methods can produce comparable WEX BBB ., Purpose: To explore whether dynamic contrast-enhanced (DCE)-MRI and vascular water exchange imaging (VEXI) could produce comparable WEX BBB in high-grade glioma (HGG) patients., Study Type: Prospective cross-sectional., Subjects: 13 HGG patients (58.4 ± 9.4 years, 9 females, 4 WHO III and 9 WHO IV)., Field Strength/sequence: A 3 T, spoiled gradient-recalled-echo DCE-MRI and VEXI containing two pulsed-gradient spin-echo blocks separated by a mixing block., Assessments: The enhanced tumor and contralateral normal-appearing white matter (cNAWM) volume-of-interests (VOIs) were drew by two neuroradiologists. And whole-brain NAWM and normal-appearing gray matter (NAGM) without tumor-affected regions were segmented by automated segmentation algorithm in FSL., Statistical Tests: Student's t-test was used to evaluate parameters difference between cNAWM and tumor, NAGM and NAWM, respectively. The correlation between vascular water efflux rate constant (k bo ) from DCE-MRI and apparent exchange rate across BBB (AXR BBB ) from VEXI was evaluated by Pearson correlation. P < 0.05 was considered statistically significant., Results: Compared with cNAWM, both k bo and AXR BBB were significantly reduced in tumor (k bo  = 3.50 ± 1.18 sec -1 vs. 1.03 ± 0.75 sec -1 ; AXR BBB  = 3.54 ± 1.11 sec -1 vs. 1.94 ± 1.04 sec -1 ). Both k bo and AXR BBB showed significantly higher values in NAWM than NAGM (k bo  = 3.50 ± 0.59 sec -1 vs. 2.10 ± 0.56 sec -1 ; AXR BBB  = 3.35 ± 0.77 sec -1 vs. 2.07 ± 0.52 sec -1 ). The VOI-averaged k bo and AXR BBB were also linearly correlated in tumor, NAWM, and NAGM (r = 0.59)., Data Conclusion: DCE-MRI and VEXI showed comparable and correlated WEX BBB in HGG patients, suggesting that the consistence and reliability of these two MRI methods in measuring WEX BBB ., Evidence Level: 2., Technical Efficacy: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura , can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.

Atezolizumab plus bevacizumab (A+B) is used to treat unresectable hepatocellular carcinoma (HCC), but the optimal rescue therapy after A+B remains unclear. Combining locoregional therapy (LRT) with systemic treatment has been shown to improve tumor control, but the role in patients who fail A+B is unknown. We retrospectively enrolled patients who experienced radiological progression after A+B. Objective response rate (ORR), disease control rate (DCR), post progression survival (PPS), and secondary progression-free survival (PFS) were evaluated by modified RECIST. Inverse probability weighting (IPW) was used to balance baseline clinical features. A total of 61 patients were enrolled with a median age of 60.7 years, 83.6% male, 88.5% viral hepatitis-related, and 60.7% without prior systemic treatment before A+B. Patients receiving sequential therapies had significantly longer PPS than supportive care (10.5 vs. 2.3 months, P<0.0001). Among 37 patients received sequential systemic treatment, 18 received combined LRT. The median follow-up after post A+B failure was 6.6 months. The combined LRT group had higher ORR (27.8 vs. 0%, P=0.0197) and DCR (72.2 vs. 26.3%, P=0.0052) than systemic alone group. The median PPS and secondary PFS were significantly longer in combined LRT group (PPS: 12.2 vs. 5.8 months, P=0.0070; PFS: 5.0 vs. 2.6 months, P=0.0134) than systemic alone group. After IPW analysis, patients with combined LRT had superior PPS and secondary PFS. The incidence rates of AEs were higher in LRT combination compared to systemic alone (any grade AEs: 94.4 vs. 63.2%, P=0.0422; severe AEs: 33.3 vs. 5.3%, P=0.0422). No significant albumin-bilirubin index changed in the first 3 months in combined LRT group (0.966 [0.647-1.443], P=0.867) though a trend of deterioration in systemic alone group. In conclusion, sequential systemic therapy provides survival benefits after A+B failure. Furthermore, combining LRT with systemic treatment could provide better tumor responses and survival benefits with acceptable toxicity than systemic therapy alone., Competing Interests: None., (AJCR Copyright © 2023.)

Cucurbitacin I (JSI-124), derived from Cucurbitaceae, has shown the potential to induce apoptosis and cell cycle arrest in some cancer cells. However, the effect of JSI-124 on glioblastoma multiforme (GBM) cell cycle and apoptosis is still unclear. Our investigation revealed that JSI-124 effectively reduced cell viability in GBM cells, leading to apoptosis and increased caspase-3 activity. Intriguingly, JSI-124 caused the accumulation of G2/M phase to regulate cell cycle, confirmed by MPM-2 staining and increased protein synthesis during mitosis by mitotic index analysis. Western blot analysis found that JSI-124 affected the progression of G2/M arrest by downregulating the CDK1 and upregulating the cyclinB1, suggesting that JSI-124 disrupted the formation and function of the cyclin B1/CDK1 complex in GBM8401 and U87MG cells. However, we found the JSI-124-regulated cell cycle G2/M and apoptosis-relative gene in GBM8401 and U87MG cells by NGS data analysis. Notably, we found that the GBM8401 and U87MG cells observed regulation of apoptosis and cell-cycle-related signaling pathways. Taken together, JSI-124 exhibited the ability to induce G2/M arrest, effectively arresting the cell cycle at critical stages. This arrest is accompanied by the initiation of apoptosis, highlighting the dual mechanism of action of JSI-124. Collectively, our findings emphasize that JSI-124 holds potential as a therapeutic agent for GBM by impeding cell cycle progression, inhibiting cell proliferation, and promoting apoptosis. As demonstrated by our in vitro experiments, these effects are mediated through modulation of key molecular targets.

Cancer drug resistance is an ever-changing problem that most patients need to face in their later stages of treatment, especially the multidrug resistant (MDR) type. The drug efflux transporters, including P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP), play the crucial roles in this sophisticated battle. In recent decades, researchers try to find potential inhibitors to impede the drug efflux function of above transporters. d-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is a prevalently used excipient in the formulation design. In the present study, the modulatory effects and mechanisms of vitamin E TPGS on the efflux transporters were investigated. And the cancer MDR reversing ability of vitamin E TPGS was evaluated as well. Stable-cloned transporter over-expressed cell lines were used for mechanisms study, while several types of MDR cancer cell lines were adopted as reversing evaluation models. The results exhibited that vitamin E TPGS significantly inhibited the efflux function of P-gp, MRP1, and BCRP under non-cytotoxic concentrations, but not influencing the protein expression levels. Through efflux assay and molecular docking, vitamin E TPGS was found to be an uncompetitive, non-competitive, and competitive inhibitor on chemotherapeutic drug doxorubicin efflux in P-gp, MRP1, and BCRP over-expressing cell lines, respectively. Furthermore, the basal ATPase activity of three transporters were significantly inhibited by vitamin E TPGS at 10 μM. And the cell membrane fluidity of P-gp over-expressing cell line was enhanced by 22.58% with 5 μM vitamin E TPGS treatment, compared to the parental Flp-In™-293 cell line (without P-gp). The resistance reversing ability of vitamin E TPGS was prominent in MCF-7/DOX MDR breast cancer cell line, which over-expressed P-gp, MRP1, and BCRP. These significant results suggested that vitamin E TPGS is a promising modulator on transporters mediated cancer MDR. Vitamin E TPGS is not an inert excipient, but possesses MDR-reversing pharmacological effects, and deserves a re-purposing application on the future combinatorial regimen design for MDR cancer treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Five species in the penaeid shrimp genus Parapenaeopsis Alcock, 1901 are reported from Taiwan. Parapenaeopsis amicus V.C. Nguyn, 1971 and P. venusta De Man, 1907 are formally recorded in Taiwan for the first time. Taxonomic problems related to the species reported from Taiwan are discussed, and a key to the species of Parapenaeopsis in Taiwan is provided.

Purpose: 3D pulse sequences enable high-resolution acquisition with a high SNR and ideal slice profiles, which, however, is particularly difficult for diffusion MRI (dMRI) due to the additional phase errors from diffusion encoding., Methods: We proposed a twin navigator-based 3D diffusion-weighted gradient spin-echo (GRASE) sequence to correct the phase errors between shots and between odd and even spin echoes for human whole-brain acquisition. We then compared the SNR of 3D GRASE and 2D simultaneous multi-slice EPI within the same acquisition time. We further tested the performance of 2D versus 3D acquisition at equivalent SNR on fiber tracking and microstructural mapping, using the diffusion tensor and high-order fiber orientation density-based metrics., Results: The proposed twin navigator approach removed multi-shot phase errors to some extent in the whole brain dMRI, and the 2D navigator performed better than the 1D navigator. Comparisons of SNR between the 2D simultaneous multi-slice EPI and 3D GRASE sequences demonstrated that the SNR of the GRASE sequence was 1.4-1.5-fold higher than the EPI sequence at an equivalent scan time. More importantly, we found a significantly higher fiber cross-section in the cerebrospinal tract, as well as richer subcortical fibers (U-fibers) using the 3D GRASE sequence compared to 2D EPI., Conclusion: The twin navigator-based 3D diffusion-weighted-GRASE sequence minimized the multishot phase error and effectively improved the SNR for whole-brain dMRI acquisition. We found differences in fiber tracking and microstructural mapping between 2D and 3D acquisitions, possibly due to the different slice profiles., (© 2023 International Society for Magnetic Resonance in Medicine.)

Gene therapy for hemophilia has been investigated for decades but no breakthroughs were made until Nathwani et al. achieved a significant and sustainable factor IX increase in hemophilia B patients in 2011. About eleven years later, in August 2022, the first hemophilia A gene therapy product was approved by the European Commission and hemophilia treatment entered a new era. This review does not focus on the newest advances but rather the practical aspects of gene therapy aiming to provide an overview for physicians who treat hemophiliacs who did not participate in the clinical trials. The current status of gene therapy, focusing particularly on products likely to be clinically available soon, are reviewed and summarized. Currently, possible limitations of gene therapy are pre-existing neutralizing antibodies toward the vector, liver health, age, and inhibitor status. Possible safety concerns include infusion reactions, liver damage, and adverse effects from immune suppressants or steroids. In summary, generally speaking, gene therapy is effective, at least for several years, but the exact effect may be unpredictable and intensive monitoring for several months is needed. It can also be considered safe with careful practice on selected patients. In its current form, gene therapy will not replace all hemophilia treatments. Advances in non-factor therapy will also improve hemophilia care greatly in the future. We envisage that gene therapy may be included in multiple novel therapies for hemophilia and benefit some hemophilia patients while novel non-factor therapies may benefit others, together fulfilling the unmet needs of all hemophilia patients., Competing Interests: Declaration of competing interest All authors have no relevant competing interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients., Methods: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death., Results: Patients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20-8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30-3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases., Conclusions: The machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction., 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., (© 2023 Chang, Liu, Huang, Hsu, Chen, Lin, Tsai, Chou, Wen, Wo, Lee, Liu, Wang and Kuo.)

The synthesis of one-dimensional zinc oxide nanorod photoelectrodes through a chemical solution method and their application in dye-sensitized solar cells are described in this paper. A multiple growth approach was used to fabricate zinc oxide nanorods with varying length-to-diameter ratios, and their dye adsorption properties were characterized using ultraviolet-visible spectroscopy. The zinc oxide photoelectrodes with different length-to-diameter ratios were subsequently incorporated into dye-sensitized solar cells, and their performance and carrier lifetime were analyzed using a solar simulator, monochromatic incident photon-to-electron conversion efficiency, and electrochemical impedance spectroscopy. The highest efficiency achieved was 0.74%. The results indicate that the quality of the zinc oxide nanorods synthesized through the multiple growth approach is consistent, with the uniformity and morphology of the nanorods having the greatest impact on device efficiency., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01-1.58), for spine fractures was 1.43 (95% CI = 1.26-1.62), for wrist fractures was 0.95 (95% CI = 0.75-1.22), and for hip fractures was 1.67 (95% CI = 1.38-2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

Three-phase crystallization (TPC) was introduced in this study to purify L -menthol from menthol enantiomer mixtures in consideration of the formation of solid solutions. TPC is a new separation technology, which combines melt crystallization and vaporization to result in the desired crystalline product from a liquid mixture along with the unwanted components vaporized via the three-phase transformation by reducing temperature and pressure. The three-phase transformation conditions for the liquid menthol enantiomer mixtures were determined based on the thermodynamic calculations to direct the TPC experiments. A new model was proposed based on the mass and energy balances in consideration of the formation of the solid solutions to predict the yield and purity of the final L -menthol product during TPC. The yield and purity obtained from the TPC experiments were compared with those predicted by the model.

Background/purpose: Providing oral healthcare education can be an optimal strategy for imparting knowledge and developing self-care skills for older adults to enhance their oral health conditions. However, traditional passive lecture-based education programs have several limitations. Integrating mobile augmented reality (MAR) into oral health education can potentially enhance the effectiveness of the education by mitigating those limitations. The objectives of this study are to develop and evaluate the effectiveness of MAR-integrated oral health education. The objectives of this study were to develop and evaluate the effectiveness of MAR-integrated oral health education., Materials and Methods: Twenty-four older adults from community dwellings participated in this study. The participants received MAR-integrated oral health education once at activity centers. Self-report questionnaires were utilized to assess oral healthcare-related knowledge and self-efficacy, and the usability score of the MAR system. The assessment was conducted before and after the educational program. Data were statistically analyzed using descriptive statistics and paired-t test., Results: The mean scores of oral healthcare-related knowledge and self-efficacy showed a significant increase after the educational program, with P -values of <0.001 and 0.002, respectively. A majority of the participants exhibited a lack of knowledge and self-efficacy regarding the proper selection of toothpaste and interdental brushes. However, there was an improvement after the intervention. The usability score of the system was lower than the average level., Conclusion: MAR-integrated oral health education effectively increases oral health-related knowledge and self-efficacy among community dwelling older adults. Still, the usability of the MAR system needs to be improved. Further investigation of long-term effects and clinical outcomes, and the inclusion of comparative groups are recommended for the future study., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Mitochondrial encephalomyopathy is a multi-system disorder mostly caused by inborn errors of the oxidative phosphorylation (OXPHOS) system and usually manifested as complex neurological disorder and muscle weakness. Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is one of the major subtypes of mitochondrial disease associated with the m.8344A>G mutation in mitochondrial tRNA Lys gene. In addition to the symptoms in central nervous and muscle systems, a portion of the patients may develop hearing loss, which has been linked to the genetic mutations of mitochondrial DNA (mtDNA) especially in the mitochondrial ribosome RNA (rRNA) gene. Despite a great number of studies focusing on the consequences of mtDNA mutations, the mechanism of pathogenesis of these overt diseases has remained unclear, and there is no specific and effective treatment for MERRF syndromes. In this study, we developed a high-quality mtDNA sequencing method by next generation sequencing technology to search for the additional pathogenic variations of mtDNA from skin fibroblasts of four members in a Taiwanese family with MERRF syndrome. Through uncovering the signatures of all mtDNA variants in the MERRF family, we identified novel mtDNA variants in the genes encoding mitochondrial 12S and 16S rRNAs. The finding from this study will give us further insight into the molecular mechanisms driving the phenotypic variability and timing of onset of the MERRF syndrome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.