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Yi-Hsuan Chuang,* Yu-Fan Cheng,* Leo Leung-Chit Tsang, Hsin-You Ou, Hsien-Wen Hsu, Wei-Xiong Lim, Po-Hsun Huang, Ching-Chun Weng, Chun-Yen Yu Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan*These authors contributed equally to this workCorrespondence: Chun-Yen Yu, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung, 833401, Taiwan, Tel +886-7-731-7123 #3027, Email y7192215@ms17.hinet.netPurpose: To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor > 8 cm or multiple tumors with the largest tumor diameter > 5 cm and total tumor diameter > 10 cm.Patients and Methods: Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded.Results: The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03– 34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP > 400 ng/mL (p = 0.0306), maximum tumor size > 10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy.Conclusion: Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.Keywords: hepatocellular carcinoma, transarterial chemoembolization, treatment response, prognosis

Interleukin (IL)-37, a unique member of the IL-1 family, is known for its anti-inflammatory properties. However, its effects on immune-mediated liver diseases, such as primary biliary cholangitis (PBC) and acute immune-mediated hepatitis, remain unclear. Using mouse models of autoimmune cholangitis and hepatitis induced by 2-OA-OVA and concanavalin A (Con A) respectively, we introduced the human IL-37 gene via a liver-preferred adeno-associated virus vector (AAV-IL-37) to mice, as mice lack endogenous IL-37. Our findings reveal that IL-37 did not affect autoimmune cholangitis. Surprisingly, IL-37 exacerbated inflammation in Con A-induced hepatitis rather than mitigating it. Mechanistic insights suggest that this exacerbation involves the interferon (IFN)-γ pathway, supported by elevated serum IFN-γ levels in AAV-IL-37-treated Con A mice. Specifically, IL-37 heightened the number of hepatic NK and NKT cells, increased the production of the NK cell chemoattractant CCL5, and elevated the frequency of hepatic NK and NKT cells expressing IFN-γ. Moreover, IL-37 enhanced IFN-γ secretion from NK cells when combined with other proinflammatory cytokines, highlighting its synergistic effect in promoting IFN-γ production. These unexpected outcomes underscore a novel role for IL-37 in exacerbating liver inflammation during immune-mediated liver diseases, implicating its influence on NK cells and the production of IFN-γ by these cells., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The skin is the largest organ of the human body and serves distinct functions in protecting the body. The viscoelastic properties of the skin play a key role in supporting the skin-healing process, also it may be changed due to some skin diseases., Propose: In this study, high-frequency ultrasound (HFUS) elastography based on a Lamb wave model was used to noninvasively assess the viscoelastic anisotropy of human skin., Method: Elastic waves were generated through an external vibrator, and the wave propagation velocity was measured through 40 MHz ultrafast HFUS imaging. Through the use of a thin-layer gelatin phantom, HFUS elastography was verified to produce highly accurate estimates of elasticity and viscosity. In a human study involving five volunteers, viscoelastic anisotropy was assessed by rotating an ultrasound transducer 360°., Results: An oval-shaped pattern in the elasticity of human forearm skin was identified, indicating the high elastic anisotropy of skin; the average elastic moduli were 24.90 ± 6.63 and 13.64 ± 2.67 kPa along and across the collagen fiber orientation, respectively. The average viscosity of all the recruited volunteers was 3.23 ± 0.93 Pa·s., Conclusions: Although the examined skin exhibited elastic anisotropy, no evident viscosity anisotropy was observed., (© 2024 American Association of Physicists in Medicine.)

mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with β-glucans (βGlus), a potential adjuvant for vaccines, encapsulated within LNPs (βGlus/mRNA@LNPs). The βGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, βGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral βGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration., (© 2024 Wiley‐VCH GmbH.)

Background: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET)., Methods: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points., Results: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96)., Conclusion: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The relationship between the psoas muscle index (PMI) and the appendicular skeletal muscle index (ASMI) in patients with compensated advanced chronic liver disease (cACLD) is not yet understood. Our goal is to determine which level of the lumbar spine best represents the appendicular skeletal muscle., Methods and Materials: This retrospective study involved patients with cACLD between January 2020 and December 2021. We documented the patients' body weight, height, gait speed, handgrip strength, appendicular skeletal muscle measured by DXA, and psoas muscle area segmented on computed tomography or magnetic resonance imaging. Low muscle mass, as defined by the Asian working group for sarcopenia, is less than 7.0 kg/m 2 in males and less than 5.4 kg/m 2 in females. We analyzed the correlation between PMI and ASMI., Results: A total of 134 patients were enrolled in the study, with 74 being male and 60 being female. The mean age was 63.9 ± 7.7 years old. Significant associations (p < 0.001) were found between PMI of all levels and ASMI. In the analysis of Pearson's correlation coefficients, it was noted that the r value increased gradually in both males (r = 0.3197 at L2, 0.4006 at L3, 0.5769 at L4) and females (r = 0.3771 at L2, 0.4557 at L3, 0.5251 at L4). Similarly, the area under the curve (AUC) values predicting low muscle mass were as follows: for males, AUC=0.582 at L2, 0.619 at L3, 0.728 at L4; for females, AUC=0.685 at L2, 0.733 at L3, 0.744 at L4. The cut-off point for PMI in males was 4.12 at L2, 6.25 at L3, and 8.48 at L4, while in females was 2.61 at L2, 4.47 at L3, 6.07 at L4., Conclusion: The Psoas muscle index can be used to assess the muscle mass status in patients with cACLD. Among the various levels that can be used, we recommend using the fourth inferior endplate of the lumbar spine, as it shows the highest correlation. Additionally, we suggest using a PMI cut-off point of 8.48 cm 2 /m 2 for males and 6.07 cm 2 /m 2 for females as a predictor of low muscle mass in Asian., 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 © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

The study aimed to translate the Geriatric Anxiety Inventory into traditional Chinese (GAI-TC), examine its psychometric properties, and identify the optimal cutoff point. This research recruited 337 older adults from two community activity centers. Structured questionnaires were used, including demographic information and characteristics, the GAI-TC, and the State-Trait Anxiety Inventory (STAI). Cronbach's α of the GAI-TC was 0.93. The intraclass correlation coefficient was 0.90. The content validity index was 1.0. An exploratory factor analysis revealed that three factors in the GAI-TC, including cognition anxiety, impact of anxiety, and somatic anxiety, explained 59.46 % of the variance. The criterion-related validity showed a significant positive correlation between the GAI-TC and STAI, with an optimal cutoff of 9/10 for detecting anxiety in older persons living in the community. The GAI-TC had good reliability and validity and can provide professionals with a tool for the early identification of anxiety among older adults., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ageism is prejudice or discrimination against different age groups, particularly older people. As senior nursing students in the last year of their studies prepare to enter the workforce, it is imperative to understand their level of ageism because of the high probability that they will care for older people during their nursing careers due to the global aging population. However, most research has focused on nursing students' knowledge and attitudes regarding older adults, and few studies have specifically investigated ageism among senior nursing students., Objective: This study aimed to understand ageism among senior nursing students and associated factors., Design: This was a cross-sectional descriptive study., Settings and Participants: In total, 249 senior students from 16 four-year Bachelor of Science in Nursing programs in Taiwan were recruited. Inclusion criteria were (1) a senior student enrolled in a Bachelor of Science in Nursing program and (2) the ability to read Chinese., Methods: Data were collected using an online questionnaire consisting of two parts: demographic characteristics and the Fraboni Scale of Ageism. The frequency, percentage, mean, standard deviation, t-test, one-way analysis of variance, Pearson product-moment correlation, and multiple linear regression were used to analyze data., Results: The average score for ageism among senior nursing students was 61.60 ± 7.73, out of a maximum of 116. Having a higher level of concern about ageism issues and having had grandparents who were primary caregivers during childhood were linked to a lower degree of ageism. The only predictor of senior nursing students' ageism was the extent of their concern about ageism issues (F = 18.47, p < .001)., Conclusions: Senior nursing students demonstrated a moderate level of ageism. Faculty members should develop strategies to increase nursing students' awareness of ageism issues and develop appropriate interventions to prevent and improve their ageist attitudes., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = -0.72 and -0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by immune-mediated destruction of intrahepatic small bile ducts. CD8 T cells play a critical role in biliary destruction. However, regulatory T cells (Tregs) have also been identified in the portal tracts of PBC patients. This study tested the hypothesis that hepatic Tregs in PBC were dysfunctional in suppressing immune responses in disease by using our human PBC-like autoimmune cholangitis (AIC) mouse model induced by 2-octynoic acid-conjugated ovalbumin (2-OA-OVA). Our results showed that female and male mice immunized with 2-OA-OVA developed AIC; however, female AIC mice had more severe liver inflammation and fibrosis than male AIC mice. Levels of functional effector CD8 T cells and their chemoattractants, CXCL9 and CXCL10, in the liver were markedly elevated in female AIC mice than in male AIC mice. These results reinforce that CD8 T cells are the primary effector cells in PBC. The number of hepatic Tregs in AIC mice was also higher than in saline-treated mice, but there was no difference between male and female AIC mice. The suppressive function of AIC Tregs was evident despite a discrepancy in the changes in their co-inhibitory receptors and inhibitory cytokines. However, the expansion of hepatic Tregs by low-dose IL-2 treatment did not reduce immune responses to AIC, which may be due to the dysfunction of Tregs in inhibiting T cells. In conclusion, the function of Tregs in the inflamed liver of PBC was insufficient, and low-dose IL-2 treatment could not restore their function to suppress pathological immune responses. Transferring normal Tregs or directly targeting effector CD8 T cells may be beneficial for treating PBC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Various treatment options are available for degenerative joint disease (DJD). During clinical visits, patients and clinicians collaboratively make decisions regarding the optimal treatment for DJD; this is the essence of shared decision-making (SDM). Here, we collated and assessed the SDM-related experiences and perspectives of outpatients with DJD in Taiwan., Design: In-depth interviews and thematic analysis., Setting: Primary care clinics of a regional teaching hospital in Taiwan, October 2021-May 2022., Participants: 21 outpatients with at least three visits for DJD and who were aware of SDM., Results: Four main themes emerged in this study: first, equipping themselves with knowledge: outpatients obtained disease-related and treatment-related knowledge in various ways-seeking relevant information online, discussing with family and friends, learning from their own experiences or learning from professionals. Second, shared or not shared: physicians had different patterns for communicating with patients, particularly when demonstrating authority, performing mutual discussion, respecting patient preferences or responding perfunctorily. Third, seldom saying no to physician-prescribed treatment plans during clinical visits: most patients respected physicians' professionalism; however, some patients rejected physicians' recommendations indirectly, whereas some responded depending on their disease prognosis. Fourth, whose call?-participants decided to accept or reject a treatment plan independently or by discussing it with their families or by obeying their physicians' recommendations., Conclusions: In general, patients with DJD sought reliable medical information from various sources before visiting doctors; however, when having a conversation with patients, physicians dominated the discussion on treatment options. The patient-physician interaction dynamics during the SDM process determined the final medical decision, which was in accordance with either patients' original autonomy or physicians' recommendations. To alleviate medical paternalism and physician dominance, patients should be empowered to engage in medical decision-making and share their opinions or concerns with their physicians. Family members should also be included in SDM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This study aimed to assess the impact of two educational modules on enhancing the communication confidence, competence and performance of perinatal nurses in the context of palliative care., Background: Concerns have arisen regarding the preparedness of perinatal nurses in delivering palliative care, especially in terms of deficiencies in communication skills and negative attitudes toward making life-support decisions for parents facing neonates with terminal conditions. Bridging this gap necessitates improved perinatal palliative care education for healthcare providers. Research has shown that simulation-based teaching effectively enhances procedural competence, communication skills and confidence among healthcare professionals. However, comprehensive curricula focusing on perinatal palliative communication remain limited., Design: This study used a quasi-experimental design employing a two-group repeated measure approach. It involved a purposive sample of 79 perinatal nurses from a hospital in northern Taiwan., Methods: A palliative communication course specifically designed for registered nurses in perinatal units was developed. Participants were allocated to either the experimental group (Scenario-Based Simulation, SBS) or the control group (traditional didactic lecture). Communication confidence and competence were assessed before and immediately after the course through structured questionnaires. Learning satisfaction was collected post-intervention and participants underwent performance evaluation by standardized parents one week later., Results: A significant training gap in palliative care exists among nurses in OB/GYN wards, delivery rooms and neonatal critical care units, highlighting the need for continuing education. All 79 participants completed the training course. Following the intervention, nurses in the SBS group (n=39) exhibited significant improvements in self-reported confidence (p <0.05), competence (p <0.01) and performance (p <0.001) in neonatal palliative communication compared with the traditional didactic lecture group (n=40). The SBS group also received higher satisfaction ratings from nurse learners (p <0.001)., Conclusions: The research findings support scenario-based simulation as a more effective educational approach compared with traditional didactic lectures for enhancing communication confidence and competence. These results were further reinforced by evaluation from standardized patients, highlighting the value of direct feedback in enhancing nurses' performance. Tailoring SBS designs to diverse nursing contexts and incorporating a flipped approach can further enrich the overall learning experience. Given its high effectiveness and positive reception, we recommend integrating this educational module into palliative care training programs for perinatal nurses., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Interactive e-books offer multimedia and interactive features that make them particularly suitable for learning nursing skills and also allow for easy content updating, ensuring that students learn the most current skills based on the latest clinical guidelines., Purpose: To examine the effectiveness of an interactive e-book in increasing nursing students' knowledge, confidence, and learning self-efficacy of performing nasogastric tube feeding., Methods: A randomized controlled trial was conducted with 62 nursing students, with the experimental group using an interactive e-book for learning whereas the comparison group using a printed textbook., Results: The experimental group demonstrated significantly greater knowledge and confidence improvements than the comparison group, but no significant difference was found in learning self-efficacy. The experimental group was significantly more satisfied with the learning materials than the comparison group., Conclusions: Interactive e-books are more effective in enhancing nursing students' knowledge and confidence in performing nursing skills than printed textbooks., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Arterial pulse-wave velocity (PWV) is widely used in clinical applications to assess cardiovascular diseases. Ultrasound methods have been proposed for estimating regional PWV in human arteries. Furthermore, high-frequency ultrasound (HFUS) has been applied to perform preclinical small-animal PWV measurements; however, electrocardiogram (ECG)-gated retrospective imaging is required to achieve high-frame-rate imaging, which might be affected by arrhythmia-related problems. In this article, HFUS PWV mapping based on 40-MHz ultrafast HFUS imaging is proposed to visualize PWV on mouse carotid artery to measure arterial stiffness without ECG gating. In contrast to most other studies that used cross-correlation methods to detect arterial motion, ultrafast Doppler imaging was applied in this study to measure arterial wall velocity for PWV estimations. The performance of the proposed HFUS PWV mapping method was verified using a polyvinyl alcohol (PVA) phantom with various freeze-thaw cycles. Small-animal studies were then performed in wild-type (WT) mice and in apolipoprotein E knockout (ApoE KO) mice that were fed a high-fat diet (for 16 and 24 weeks). The Young's modulus of the PVA phantom measured through HFUS PWV mapping was 15.3 ± 0.81, 20.8 ± 0.32, and 32.2 ± 1.11 kPa for three, four, and five freeze-thaw cycles, respectively, and the corresponding measurement biases (relative to theoretical values) were 1.59%, 6.41%, and 5.73%, respectively. In the mouse study, the average PWVs were 2.0 ± 0.26, 3.3 ± 0.45, and 4.1 ± 0.22 m/s for 16-week WT, 16-week ApoE KO, and 24-week ApoE KO mice, respectively. The PWVs of ApoE KO mice increased during the high-fat diet feeding period. HFUS PWV mapping was used to visualize the regional stiffness of mouse artery, and a histology confirmed that the plaque formation in the bifurcation region increased the regional PWV. All the results indicate that the proposed HFUS PWV mapping method is a convenient tool for investigating arterial properties in preclinical small-animal studies.

Although the relationships of cerebrovascular hemodynamic dysfunction with neurodegenerative diseases remain unclear, many studies have indicated that poor cerebral perfusion accelerates the progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Small animal models are widely used in AD research. However, providing an imaging modality with a high spatiotemporal resolution and sufficiently large field of view to assess cerebrovascular hemodynamics in vivo remains a challenge. The present study proposes a novel technique for high-spatiotemporal-resolution vector micro-Doppler imaging (HVμDI) based on contrast-free ultrafast high frequency ultrasound imaging to visualize the cerebrovascular hemodynamics of the mouse, with a data acquisition time of 0.4 s, a minimal detectable vessel size of 38 µm, and a temporal resolution of 500 Hz. In vivo experiments are conducted on wild-type and AD mice. Cerebrovascular hemodynamics are quantified using the cerebral vascular density, diameter, velocity, tortuosity, cortical flow pulsatility, and instant flow direction variations. Results reveal that AD significantly change the cerebrovascular hemodynamics. HVμDI offers new opportunities for in vivo analysis of cerebrovascular hemodynamics in neurodegenerative pathologies in preclinical animal research., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aims: This study aimed to evaluate the critical thinking abilities of senior nursing students in Vietnam and determine factors associated with their critical thinking disposition and skills., Background: Assessing critical thinking competence is crucial for determining senior nursing students' preparedness for entering the healthcare workforce and can be used to examine current nursing education's ability to cultivate nursing students' critical thinking. However, little research was found on critical thinking among Vietnamese nursing students., Design: A multicenter cross-sectional research design., Methods: A convenience sample of 533 senior nursing students from six universities in Vietnam participated in this study. All participants completed the online questionnaires, including basic information, a subscale of the Motivated Strategy for Learning Questionnaire (MSLQ), Critical Thinking Disposition Scale (CTDS), and Critical Thinking Self-Assessment Scale (CTSAS)., Results: The mean score for the CTDS was 42.81 (standard deviation (SD) = 5.29), while the mean score for the CTSAS was 168.29 (SD = 44.43). Results of the multiple linear-regression analysis showed that an increase in self-study hours per day (B = 0.41, p = 0.007), higher self-efficacy in learning and performance (B = 0.26, p < 0.001), and a more-supportive environment (B = 0.97, p < 0.001) were predictors of critical thinking disposition. Moreover, an increase in self-study hours per day (B = 4.09, p = 0.001), higher self-efficacy in learning and performance (B = 2.65, p < 0.001), a more-supportive environment (B = 7.74, p < 0.001), and more experience with research (B = 7.03, p = 0.03) were predictors of critical thinking skills., Conclusions: This study revealed that senior nursing students in Vietnam possess a moderate level of critical thinking abilities. Those students who dedicate more hours to self-study, demonstrate higher self-efficacy in learning and performance, experience a supportive environment, and engage in more research activities exhibit better critical thinking disposition and skills. The findings highlight the ongoing need to enhance critical thinking disposition and skills of nursing students in Vietnam. It is suggested that nursing faculty members should develop the appropriate strategies to improve nursing students' critical thinking disposition and skills., 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.)

Breakpoint chlorination is prevalent in drinking water and potable reuse water treatment. Breakpoint chlorination enhances the formation of N -nitrosamines through reactions that form nitrosating agents. The most recent study suggests that nitroxyl (HNO) can react with free chlorine (HOCl) to form the nitrosyl chloride (ClNO) nitrosating agent but has not experimentally verified its importance in breakpoint chlorination. This study first assessed the formation of N -nitrosamines from model N -chloro-alkylamine precursors when they were added to a mixture of HOCl and HNO-derived nitrosating agents generated by chlorinating hydroxyurea. Results demonstrated negligible N -nitrosamine formation. Instead, we observed that the interaction of NCl 3 with NHCl 2 (total Cl 2 /total N molar ratio = 2.4-3:1) produced an intermediate capable of nitrosating N -chloro-alkylamines to N -nitrosamines at yields 8-fold higher to those observed in NHCl 2 treatment alone, within a very short timescale (<3 min). We examined the stoichiometry of the reaction of NCl 3 with NHCl 2 using a UV-spectrum-based approach. Nitrosyl chloride was proposed as the key intermediate, likely formed alongside the reformation of NHCl 2 . Further isotopic experiments, byproduct measurements, and kinetic modeling supported the hypotheses. Modeling indicated that the reaction of NCl 3 with NHCl 2 explained ∼75% of NDMA formation during breakpoint chlorination. Because NCl 3 is mainly derived from the reaction of HOCl with NHCl 2 , controlling NHCl 2 (e.g., with additional treatment) is critical for minimizing nitrosamine formation in waters where breakpoint chlorination occurs.

The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration., 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.)

Head and neck squamous cell carcinoma (HNSC) exhibits genetic heterogeneity in etiologies, tumor sites, and biological processes, which significantly impact therapeutic strategies and prognosis. While the influence of human papillomavirus on clinical outcomes is established, the molecular subtypes determining additional treatment options for HNSC remain unclear and inconsistent. This study aims to identify distinct HNSC molecular subtypes to enhance diagnosis and prognosis accuracy. In this study, we collected three HNSC microarrays ( n = 306) from the Gene Expression Omnibus (GEO), and HNSC RNA-Seq data ( n = 566) from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) and validate our results. Two scoring methods, representative score (RS) and perturbative score (PS), were developed for DEGs to summarize their possible activation functions and influence in tumorigenesis. Based on the RS and PS scoring, we selected candidate genes to cluster TCGA samples for the identification of molecular subtypes in HNSC. We have identified 289 up-regulated DEGs and selected 88 genes (called HNSC88) using the RS and PS scoring methods. Based on HNSC88 and TCGA samples, we determined three HNSC subtypes, including one HPV-associated subtype, and two HPV-negative subtypes. One of the HPV-negative subtypes showed a relationship to smoking behavior, while the other exhibited high expression in tumor immune response. The Kaplan-Meier method was used to compare overall survival among the three subtypes. The HPV-associated subtype showed a better prognosis compared to the other two HPV-negative subtypes (log rank, p = 0.0092 and 0.0001; hazard ratio, 1.36 and 1.39). Additionally, within the HPV-negative group, the smoking-related subgroup exhibited worse prognosis compared to the subgroup with high expression in immune response (log rank, p = 0.039; hazard ratio, 1.53). The HNSC88 not only enables the identification of HPV-associated subtypes, but also proposes two potential HPV-negative subtypes with distinct prognoses and molecular signatures. This study provides valuable strategies for summarizing the roles and influences of genes in tumorigenesis for identifying molecular signatures and subtypes of HNSC.

Background: The Critical Thinking Disposition Scale is a valid and reliable tool for assessing an individual's attitudes towards critical thinking. However, it is unclear if the scale can be used with Vietnamese nursing students., Objectives: This study aimed to translate the scale into Vietnamese and examine the psychometric properties of the Vietnamese version of the Critical Thinking Disposition Scale (CTDS-V)., Settings: Data were collected from senior nursing students at four universities in southern Vietnam in October and December 2022., Participants: In total, 398 senior nursing students participated in this study., Methods: A cross-cultural adaptation of the CTDS-V was carried out with participants obtained through convenience sampling. Data were collected through an online survey. The study evaluated the validity of the CTDS-V by examining the content validity, concurrent validity, and construct validity, employing both Exploratory and Confirmatory Factor Analyses. The study also reported the internal consistency reliability using Cronbach's alpha and test-retest stability of the CTDS-V., Results: The CTDS-V had a good content validity index with a score of at least 0.85 for each item and an excellent overall content validity index of 0.96. Exploratory Factor Analysis identified two factors, critical openness, and reflective scepticism, with 11 items. Confirmatory Factor Analysis provided an acceptable fit model and supported the factor structure of the original scale. Cronbach's alpha coefficient of the scale was 0.88, and those of the two subscales were each 0.84. The test-retest stability of the CTDS-V was good with an intraclass correlation coefficient of 0.98 (95 % confidence interval = 0.96, 0.99)., Conclusions: This study indicated that the CTDS-V is a valid and reliable tool for assessing the critical thinking disposition of nursing students. The scale is short, rendering it feasible for regular use in education and research., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although associations among insomnia, cognitive impairment, and stroke have been demonstrated, whether insomnia increases the risk of cognitive impairment after stroke remains unclear. The aim of this study was to examine whether insomnia complaints moderated the association between stroke and cognitive impairment in older adults. This study was a secondary data analysis that used data from the National Health Interview Survey 2009. A total of 447 older adults with a mean age of 74.63 years (50.1% men) were included. Self-reported insomnia and stroke occurrence were determined using a questionnaire. Cognitive impairment was assessed using the Mini-Mental State Examination. We used multivariate logistic regression to analyze the association between insomnia complaints and cognitive impairment. Participants were categorized into four groups: those with stroke and insomnia (58), those with stroke without insomnia (91), those without stroke with insomnia (116), and those without stroke or insomnia (182). The prevalence of insomnia complaints was 38.9%, and the frequency of poststroke cognitive impairment was 50.3%. After controlling for potential confounders, participants with stroke (with or without insomnia) had a significantly higher risk of cognitive impairment than those without stroke or insomnia (adjusted odds ratios: 4.16 and 2.91, 95% confidence intervals: 1.91-9.07 and 1.56-5.43, respectively). Stroke with or without insomnia complaints was associated with a higher risk of cognitive impairment relative to older adults without stroke or insomnia. The risk of cognitive impairment was the highest among participants with both stroke and insomnia., Competing Interests: Conflict of interestThe authors have no conflicts of interest relevant to this article to disclose., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 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.)

Background/aim: In diffuse large B-cell lymphoma (DLBCL), sarcopenia is associated with increased side-effects of chemotherapy and poor survival, especially in elderly patients. Anemia, a complex condition resulting from cancer itself and inflammation, might have a correlation with loss of muscle mass and might also indicate a worse outcome. In this study, we aimed to investigate the association of the skeletal muscle index (SMI) at the third lumbar vertebra (L3) with hemoglobin (Hb) levels and its predictive value for the outcome of DLBCL., Patients and Methods: The study included patients, aged 70 or older, newly diagnosed with DLBCL who received immunochemotherapy. Sex-specific L3-SMI was measured by computed tomography, and Hb levels before treatment were recorded. The Kaplan-Meier method and Cox regression model were used to analyze survival and prognostic factors., Results: Anemia was correlated with a low SMI. The presence of either low L3-SMI or anemia (Hb <10.5 g/l) indicated a poor prognosis for both progression-free and overall survival. A novel score combining L3-SMI, and Hb and lactate dehydrogenase levels as independent predictive factors was proposed for treatment response, progression-free and overall survival after adjusting for International Prognostic Index., Conclusion: This study highlights the importance of sarcopenia and anemia in patients with DLBCL, particularly in the elderly population. The proposed novel score combining L3-SMI, Hb, and lactate dehydrogenase may provide additional prognostic information for patients with DLBCL, aiding in treatment decisions and management., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology. Methods: Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments. Results: We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a 1 . This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR. Conclusion: Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Nitrite (NO 2 - ) is one of the common salts in aqueous aerosols, and its photolytic products, nitric oxide (NO) and hydroxyl radical (OH), have potential for use in the oxidation of organic matter, such as dissolved formaldehyde, methanediol (CH 2 (OH) 2 ), which is regarded as the precursor of atmospheric formic acid. In this work, the simulation of UVA irradiation in an aqueous mixture of NaNO 2 /CH 2 (OH) 2 was carried out via continuous exposure with a 365 nm LED lamp, and the reaction evolutions were probed by in situ and real-time infrared and Raman spectroscopy, which provided multiplexity in the identification of the relevant species and the corresponding reaction evolution. Although performing infrared absorption measurements in aqueous solution seemed impracticable due to the strong interference of water, the multiplexity of the vibrational bands of parents and products in the non-interfered infrared regimes and the conjunction with Raman spectroscopy still make it possible to perform in situ and real-time characterization of the photolytic reaction in the aqueous phase, supplementary to chromatographic approaches. During the 365 nm irradiation, NO 2 - and CH 2 (OH) 2 gradually decreased, concomitant with the formation of nitrous oxide (N 2 O) and formate (HCOO - ) in the early period and carbonate (CO 3 2- ) in the late period, as revealed by the vibrational spectra. The losses or the gains of the aforementioned species increased with increases in the concentration of CH 2 (OH) 2 and the irradiation flux of the 365 nm UV light. The ionic product HCOO - was also confirmed by ion chromatography, but oxalate (C 2 O 4 2- ) was absent in the vibrational spectra and ion chromatogram. The reaction mechanism is reasonably proposed on the basis of the evolutions of the aforementioned species and the predicted thermodynamic favorableness.

This study aimed to explore the efficacy of single and combined effects of exercise and branched-chain amino acid (BCAA) supplements on improving frailty and quality of life in older adults. In total, 120 study participants were allocated into a combined exercise-and-BCAA supplementation group, an exercise-only group, a BCAA supplementation-only group, and a control group. Results showed that Fried's frailty score significantly decreased in the combined exercise-and-BCAA supplementation group (β= -1.73, p<0.001), exercise-only group (β= -1.68, p<0.001), and BCAA supplementation-only group (β= -0.73, p=0.005) compared to the control group. Moreover, the combination of exercise and BCAA supplements and the exercise-only program produced significant improvements in frailty compared to the BCAA supplement-only group and control group (p<0.05). Exercise should be a critical approach for older adults to improve frailty. Healthcare professionals in geriatric care should incorporate exercise programs as frailty management and prevention for older adults., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is variability in the reported prevalence of stress and anxiety among nursing students across studies, and few studies have investigated the pooled prevalence of stress and anxiety of these students., Purpose: To investigate the prevalence and associated factors related to stress and anxiety among nursing students., Methods: Various electronic databases were searched up to October 26, 2022. A random-effects model and a moderator analysis were used to examine the overall prevalence and related factors. Begg's test was adopted to examine publication bias., Results: In total, 121 studies were included in the meta-analysis. Most nursing students experienced moderate stress (42.1%) and mild to moderate anxiety (19.4%-25.1%). Third- and fourth-year nursing students had severe stress levels compared with those in the first and second years (29.0% vs 15.1%)., Conclusions: Nurse educators should design appropriate curricula to strengthen student knowledge and provide regular assessments and supportive interventions to reduce stress and anxiety., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium's native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study's primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp.

Although water may affect aqueous aerosol chemistry, how it intervenes in the formation of secondary organic aerosols (SOAs) at the molecular level remains elusive. Ozonolysis of limonene is one of the most important sources of indoor SOAs. Here, we report the valence electronic properties of limonene aerosols and SOAs derived from limonene ozonolysis (Lim-SOAs) via aerosol vacuum ultraviolet photoelectron spectroscopy, with a focus on the effects of water on Lim-SOAs. The first vertical ionization energy of limonene aerosols is measured to be 8.79 ± 0.07 eV. While water significantly increases the total photoelectron yield of Lim-SOAs, three photoelectron features attributable to Lim-SOAs each exhibit distinct dependence on the fraction of water in aerosols, implying that different formation pathways and molecular origins are involved in the formation of Lim-SOAs. Combined with density functional theory calculation and mass spectrometry measurements, this study reveals that water, particularly the water dimer, enhances the formation of Lim-SOAs by altering the ozonolysis energetics and pathways by intervening in its Criegee chemistry, acting as both a catalyst and a reactant. The atmospheric implication is discussed.

Sunlight-induced photoirradiation of chlorine (sunlight/chlorine) can be observed in outdoor swimming pools and open-channel disinfection units for wastewater treatment. In this study, the degradation of ketamine, an environmentally persistent pharmaceutical, under sunlight irradiation in the presence of a low concentration of chlorine (1 mg/L as Cl 2 ) was investigated to elucidate the evolution of reactive species and their contribution to ketamine removal. •OH dominates the initial stage of sunlight/chlorine; however, after chlorine depletion, reactions still progress with an observed rate constant (k obs  = 7.6 ± 0.50 × 10 -3 min -1 ) an order of magnitude higher than photolysis alone (k obs  = 2.9 ± 0.15 × 10 -4 min -1 ). When chlorine is depleted, O 3 becomes the major reactant that degrades ketamine. High O 3 yields were found in both sunlight/HOCl (12.5 ± 0.5% at pH 5) and sunlight/ClO - (10 ± 1% at pH 10) systems. At sub-µM levels, O 3 resulted in substantial removal of ketamine, and even faster rates were observed in the presence of sunlight. A kinetic model was also established, and evaluate time-dependent concentration levels during sunlight/chlorine. The model simulation showed that the cumulative O 3 concentration could reach 0.91 μM, and O 3 contributed 31% ketamine removal during the sunlight/chlorine process. Primary and secondary amine functional groups were demonstrated to be the reaction sites of O 3 ; other pharmaceuticals, such as atenolol and metoprolol, underwent similar phenomena. In addition, the experimental and model results further indicated that sunlight/ClO 2 - or ClO 2 also participates in the degradation of ketamine with a minor role; trace amounts (below nM level) of ClO 2 - and ClO 2 were estimated by the simulation., 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.)

Aim: To understand the prevalence of depressive symptoms among foreign caregivers and the associated factors., Design: A cross-sectional study., Methods: Data from 178 Indonesian foreign caregivers, selected based on convenience and snowball sampling in Taiwan, were collected between July 2019 and February 2020 using questionnaires. Stepwise multiple linear regression was used to identify the factors associated with depressive symptoms., Results: Approximately 30.3% of the foreign caregivers displayed depressive symptoms. The symptoms were more prevalent among the participants who were younger; had more social support; shared a bed with others; and experienced higher work-related stress, more loneliness and physical discomfort. The findings suggest that nurses or nurse practitioners visiting patients at home should not only deliver care for them but also show concern for the psychological well-being of the foreign caregivers of these patients. Moreover, interventions should be developed to alleviate or prevent the emergence of depressive symptoms among foreign caregivers., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units., Competing Interests: Declaration of competing interest The concept of this work has filed an application of a United States patent with the University of Macau as the assignee. This patent application is pending with publication number US20200093415A1., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The 15-item Geriatric Depression Scale (GDS-15) is widely used to screen for depressive symptoms among older populations. This study aimed to develop and validate a questionnaire-free, machine-learning model as an alternative triage test for the GDS-15 among community-dwelling older adults. The best models were the random forest (RF) and deep-insight visible neural network by internal validation, but both performances were undifferentiated by external validation. The AUROC of the RF model was 0.619 (95% CI 0.610 to 0.627) for the external validation set with a non-local ethnic group. Our triage test can allow healthcare professionals to preliminarily screen for depressive symptoms in older adults without using a questionnaire. If the model shows positive results, then the GDS-15 can be used for follow-up measures. This preliminary screening will save a lot of time and energy for healthcare providers and older adults, especially those persons who are illiterate., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Susanty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the increasing threat of metabolic syndromes, a focus on maintaining kidney health from early- to mid-adulthood is necessary. This study elucidates mortality risk and years of life lost (YLLs) due to abnormal renal function. This was a retrospective, matched cohort study from health checkup data from 2000 to 2015. We identified 12,774 participants with abnormal renal function (eGFR < 60 mL/min/1.73 m 2 ) and used propensity score matching to identify 25,548 participants with normal renal function (eGFR ≥ 60). YLLs were estimated using the life expectancy differences between the abnormal and matched normal cohorts. Cox models were used to estimate the adjusted mortality risk. The estimated life expectancy of participants with proteinuria and eGFR < 60 was 26.24 years, with a 95 % confidence interval of (23.96, 29.36), 17.62 (16.37, 18.78), and 11.70 (11.02, 12.46) for age groups of 30 - 54, 55 - 64, and 65 - 79 years, respectively. The estimated YLLs of participants with proteinuria and eGFR < 60, as compared with the matched normal cohort, were 17.86 (13.41, 20.36), 12.55 (11.41, 13.78), and 8.31 (7.47, 9.13) years for the three age groups, respectively. The Cox model estimates of mortality hazard ratios of participants having proteinuria and eGFR < 60 against matched referents were 5.29 (3.97, 7.05), 3.99 (3.34, 4.75), and 3.05 (2.62, 3.55) for the three age groups, respectively. Abnormal renal function shortens life expectancy, particularly in patients with proteinuria and in younger adults. Active health management of renal function can reduce the disease burden., Competing Interests: 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., (© 2023 The Author(s).)

Castor cake is a major by-product generated after castor oil extraction and has been widely used as an organic fertilizer. Once applied to soil, a toxic alkaloid ricinine in castor cake may be released into soils and subsequently taken up by crops, which poses a potential threat to food safety and human health. However, the environmental fate of castor cake derived ricinine in agroecosystems remains unclear. In this study, the release and metabolism of ricinine in soils were conducted using soil pot experiments with different castor cake application rates. The analytical methodology of ricinine quantification in soil pore water was first established using solid phase extraction (SPE) coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A non-target screening workflow associated with LC-QTOF/MS and SIRIUS platform was further developed to identify ricinine metabolites in soil pore water. After castor cake application, the ricinine concentrations in soil pore water significantly increased to 297-7990 μg L -1 at 1 day and then gradually decreased to 62.1-3460 μg L -1 at 7 days and 1.70-279 μg L -1 at 14 days for the selected two tested soils with castor cake application rates of 2, 10, and 20 g castor cake/kg soil. In addition, two ricinine metabolites R-194 and R-180 were tentatively identified and one ricinine metabolite N-demethyl-ricinin was confirmed through authentic reference standard for the first time by the developed non-target screening workflow. This study highlights the release and metabolism of toxic alkaloid ricinine in soils once applied castor cake as an organic fertilizer. Ricinine could be released into soil pore water in a short-term after castor cake application and then undergo demethylation, hydroxylation, and hydroxylation followed by methylation metabolisms over time in agroecosystems., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model. We report herein that apoptosis of BECs was notable in the early stage of murine AIC. An altered gut microbiota, in particular, an increased percentage of gram-positive Firmicutes in AIC mice was also observed. BECs in AIC mice expressed adhesion molecule ICAM-1, cytokines/chemokines TNF-α, CCL2, CXCL9, CXCL10, and toll-like receptor (TLR) 2. Moreover, BECs treated with TLR2 ligand had elevated apoptosis and CXCL10 production. These data collectively suggest a new mechanism of tolerance breakdown in AIC. Altered gut microbiota induces apoptosis of BECs through TLR2 signaling. BECs secrete chemokines to recruit CD8 T cells to damage BECs further., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier B.V.)

Background: To examine factors that affect the severity of pyloric hypertrophy, post-operative feeding and nutritional recovery in infantile hypertrophic pyloric stenosis (IHPS)., Methods: Medical records of infants diagnosed with IHPS at a single tertiary center between 2009 and 2018 were retrospectively reviewed. Clinical characteristics, biochemistry data and outcome were assessed for their association with the severity of pyloric hypertrophy and post-operative recovery. Nutritional recovery was assessed using weight-for-age status improvement after surgery., Results: Eighty-five patients were recruited in this study. The mean pre-operative weight-for-age percentile was 18.2. Elevated bicarbonate was positively correlated with symptom duration (p = 0.007). Pyloric muscle thickness was significantly correlated with age, weight, and symptom duration (p = 0.004, 0.003, 0.008, respectively). The mean weight-for-age percentile increased to 41.6 by post-operative weeks 6-8. Pyloric muscle thickness was negatively correlated with nutritional recovery by post-operative weeks 6-8 (p = 0.003). In multivariable analysis, pyloric length related to nutritional recovery at week 1-2 postoperatively (OR = 1.42, p = 0.030, 95% CI = 0.03-1.94), and pyloric muscle thickness related to nutritional recovery at week 6-8 postoperatively (OR = 4.08, p = 0.032, 95% CI = 1.13-14.7)., Conclusion: Our study indicated that favorable nutritional outcome and successful weight gain was observed 6-8 weeks after surgery in children with IHPS. Pyloric muscle thickness positively correlated with age, weight, symptom duration, and favorable nutritional recovery. Serum bicarbonate showed a positive correlation with symptom duration., Competing Interests: Conflicts of interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

This study aims to explore how the families of patients with cancer respond to and act toward complementary and alternative medicine (CAM) use. A qualitative research design based on grounded theory was adopted in this study. Semistructured and face-to-face in-depth interviews were conducted. Each participant was involved in a one-to-one individual interview. Five categories emerged regarding how the families of patients with cancer responded to and acted toward CAM use: purposes of using CAM, CAM use between patients and families, role of family caregivers, actions when using CAM, and seeking religious practice. The core category following coding emphasized the paramount importance of patients' comfort. The findings revealed that the families of patients with cancer may respond and act differently regarding patients' use of CAM. During this process, patients may not inform family members that they are using CAM. Health care professionals should consider this in their interactions with family members., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The postoperative bleeding complications associated with laser surgery of the prostate and transurethral resection of the prostate (TURP) were compared., Methods: We used the Taiwan National Health Insurance Research Database to conduct an observational population-based cohort study. All eligible patients who received transurethral procedures between January 2015 and September 2018 were enrolled. Patients who received laser surgery or TURP were matched at a ratio of 1:1 by using propensity score matching, and the association of these procedures with bleeding events was evaluated., Results: A total of 3302 patients who underwent elective transurethral procedures were included. The multivariable Cox regression analysis revealed that diode laser enucleation of the prostate (DiLEP) resulted in significantly higher emergency room risks within 90 days after surgery due to clot retention than the Monopolar transurethral resection of the prostate (M-TURP) (Hazard Ratio: 1.52; 95% Confidence Interval [CI], 1.06-2.16, p = 0.022). Moreover, GreenLight photovaporization of the prostate (PVP) (0.61; 95% CI, 0.38-1.00 p = 0.050) and thulium laser vaporesection of the prostate (ThuVARP) (0.67; 95% CI, 0.47-0.95, p = 0.024) resulted in significantly fewer rehospitalization due to clot retention than did M-TURP. No significant increase in blood clots were observed in patients using comedications and those with different demographic characteristics and comorbidities., Conclusions: Among the investigated six transurethral procedures for Benign prostatic hyperplasia, PVP and ThuVARP were safer than M-TURP because bleeding events and clot retention were less likely to occur, even in patients receiving anticoagulant or antiplatelet therapy. However, DiLEP and holmium laser enucleation of the prostate (HoLEP) did not result in fewer bleeding events than M-TURP.

Modern education attaches great importance to interdisciplinary skills, among which computational thinking is a core element, and heralds a new era. IT application has shaped education in the 21st century. Computational thinking has provided further impetus for building an all-encompassing social network and fostering a DIY culture enabled by digital technologies. One empirical study used four apps to test children's development in computational thinking and fluency. The article will help students overcome their fears of coding. Peer reviews provide students with an opportunity to learn from each other and become more motivated. These reviews also serve as feedback for teachers to evaluate students' performance. Experimental design is used in this study, and a peer review system is implemented. Freshmen attending a programming class in a university are used as samples. At the class, students write computer programs with f-Chart, which provides a graphical user interface for students to learn programming logic and design. Zuvio, a cloud-based interactive response system, is used to conduct the peer reviews. The data of this study are analyzed through R. The results show not only an improvement in students' learning performance but also a gap between students' peer review scores and teachers' evaluation scores. Learning feedback and evaluation is crucial to transform education between students and teachers into a sustainable cycle system., 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 Hsiao, Chuang, Chen, Chang and Chen.)

Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters. In CLP models, HLJ1 deletion reduces IFN-γ expression and sepsis mortality rate when mice are treated with antibiotics. HLJ1 deficiency also leads to reduced serum levels of IL-12 in LPS-treated mice, contributing to dampened production of IFN-γ in natural killer cells but not CD4 + or CD8 + T cells, and subsequently to improved survival rate. Adoptive transfer of HLJ1-deleted macrophages into LPS-treated mice results in reduced IL-12 and IFN-γ levels and protects the mice from IFN-γ-dependent mortality. In the context of molecular mechanisms, HLJ1 is an LPS-inducible protein in macrophages and converts misfolded IL-12p35 homodimers to monomers, which maintains bioactive IL-12p70 heterodimerization and secretion. This study suggests HLJ1 causes IFN-γ-dependent septic lethality by promoting IL-12 heterodimerization, and targeting HLJ1 has therapeutic potential in inflammatory diseases involving activated IL-12/IFN-γ axis., Competing Interests: WL, SY, CC, MC, YC, KL, PL, KC, YC, JC, PY, KS No competing interests declared, (© 2022, Luo et al.)

Aim: This study aimed to examine the effectiveness of an educational board game in improving nursing students' medication knowledge., Background: Maintaining patient safety is a core practice for nurses. Medication management is a central principle of patient safety. Nurses acquire pharmacology knowledge and medication safety skills in the classroom training. Thus, solidifying and strengthening nursing students' medication knowledge are crucial tasks for nursing faculty members. In recent years, board games, which offer both entertainment and competitive play, have been employed to educate students in a variety of disciplines and settings. Through board game play, students can learn in an enjoyable and fun atmosphere., Design: A randomized controlled trial design., Methods: A convenience sample of 69 nursing students was obtained from a university in Taiwan. Participants were randomly assigned either to an experimental (board game) group (n = 35) or a comparison group (n = 34) using block randomization. The experimental group engaged in board game play to learn about medications, whereas the comparison group attended a one-hour didactic lecture. Using questionnaires, data were collected before the intervention, immediately post intervention and one month post intervention., Results: Following the intervention, regardless of the learning method, both groups showed significant improvements in their immediate recall of medication information. However, when retested after one month, the experimental group obtained significantly higher scores than the comparison group. Moreover, students in the experimental group reported more satisfaction with the learning method than those in the comparison group., Conclusions: The study results suggest that learning through board games could enhance nursing students' retention of knowledge. Students reported favorable reactions to using a board game learning method for increasing knowledge of medication. With respect to this finding, faculty members may consider employing board games as teaching tools in nursing and other health science courses. Moreover, the findings of this study can also provide additional information for nursing managers in hospital wards or long-term care facilities where nurses are trained to familiarize themselves with frequently administered medications., Tweetable Abstract: Board game play can enhance nursing students' retention of knowledge; students reported positive reactions to game-based learning for medication training., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Acute cellular rejection (ACR) is a major immune occurrence post-liver transplant that can cause abnormal liver function. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) can be used to evaluate liver disease, but it has not been utilized in the diagnosis of ACR post-liver transplant. Therefore, the purpose of this study is to evaluate the diagnostic performance of BOLD MRI and to monitor treatment response in recipients with ACR., Methods: This prospective study was approved by the local institutional review board. Fifty-five recipients with highly suspected ACR were enrolled in this study. Each patient underwent hepatic BOLD MRI, blood biochemistry, and biopsy before treatment. Of 55 patients, 19 recipients with ACR received a follow-up MRI after treatment. After obtaining the R2* maps, five regions-of-interest were placed on liver parenchyma to estimate the mean R2* values for statistical analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of R2* values in detecting patients with ACR., Results: The histopathologic results showed that 27 recipients had ACR (14 mild, 11 moderate, and 2 severe) and their hepatic R2* values were significantly lower than those of patients without ACR. ROC analysis revealed that the sensitivity and specificity of the R2* values for detection of ACR were 82.1% and 89.9%, respectively. Moreover, the R2* values and liver function in patients with ACR significantly increased after immunosuppressive treatment., Conclusion: The non-invasive BOLD MRI technique may be useful for assessment of hepatic ACR and monitoring of treatment response after immunosuppressive therapy., Key Points: • Patients with acute cellular rejection post-liver transplant exhibited significantly decreased R2* values in liver parenchyma. • R2* values and liver function were significantly increased after immunosuppressive therapy. • R2* values were constructive indicators in detecting acute cellular rejection due to their high sensitivity and specificity., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)