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Aim: Physician visual assessment (PVA) in invasive coronary angiography (ICA) is clinically used to determine stenosis severity and guide coronary intervention. However, PVA provides limited information regarding the haemodynamic significance of stenosis. This prospective study aimed to develop a model combining visual diameter stenosis (DS PVA ) and quantitative coronary angiography (QCA)-derived parameters to diagnose ischaemic lesions using invasive fractional flow reserve (FFR) with pharmacologically induced maximal hyperaemia as the gold standard., Methods: A total of 103 patients (148 lesions) who underwent ICA and FFR measurement were included in the study. Quantitative coronary angiography was used to evaluate various parameters, including anatomical parameters such as lesion length (LL), minimal lumen diameter (MLD), and minimal lumen area, along with haemodynamic parameters like LL/MLD 4 and stenotic flow reserve (SFR). Plaque area, a characteristic parameter of plaque, was also assessed. Lesion-specific ischaemia was defined as invasive FFR ≤0.8., Results: The LL/MLD 4 (r= -0.66, p<0.001) and SFR (r=0.66, p<0.001) exhibited inverse and positive correlations, respectively, with invasive FFR. In the multivariable logistic regression analysis, LL/MLD 4 (≥10.6 mm -3 vs <10.6 mm -3 ; Odds ratio [OR] 10.59, 95% confidence interval [CI] 3.94-28.50; p<0.001) and SFR (≤2.85 vs >2.85; OR 4.38, 95% CI 1.63-11.79; p=0.004) were identified as the optimal dichotomised predictors for discriminating ischaemia. The area under the curve (AUC) was 0.77 using DS PVA ≥70% as a single predictor. Adding LL/MLD 4 ≥10.6 mm -3 and SFR ≤2.85 into the model significantly increased the AUC to 0.87 (p<0.001)., Conclusion: Incorporating QCA-derived haemodynamic parameters provided significant incremental value in the model's discriminatory capability for ischaemic lesions compared with visual diameter assessment alone., Competing Interests: Declaration of Competing Interest K.K.Y. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, Novartis (via institution); Consulting fees from Abbott Vascular, Medtronic, Novartis, Peijia Medical; Speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Shockwave Medical, Amgen, Novartis, Astra Zeneca, Microport, Terumo, Omnicare. K.K.Y. is also co-founder and owns equity in Trisail for which Orbus Neich is an investor., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Despite the paucity of scientific evidence, complementary and alternative medicine (CAM) is widely used for the prevention and treatment of chronic illness, holistic care, and counteracting the adverse effects of conventional therapies. This study aims to determine the prevalence of CAM use and its associated factors among patients undergoing hemodialysis (HD) in Taiwan., Methods: This quantitative study was conducted from August 2022 to July 2024 in the HD unit at Kaohsiung Chang Gung Memorial Hospital in Taiwan. Face-to-face questionnaire-based interviews were held with 154 of 163 eligible patients (response rate, 94.5%) at the bedside during HD. The completed questionnaires were entered into a secure computer database. Data was performed by descriptive analysis, Chi-square, and Fisher tests., Results: More than half of the patients were CAM users (n = 86; 56%), and women was associated with significantly more usage of CAM. Fifty-six CAM users took Chinese herbal medicine (CHM), 52.3% (n = 45) used dietary supplements, and 19.8% (n = 17) used acupuncture. The benefit in the effectiveness of CAM was the main reason for use, the need of CAM to improve the well-being and HD-related complication was high. 32.7% of patients had used CAM based on recommendation from their family and friends. More than one-third (33.7%) of patients did not disclose their use of CAM to their doctors, most of them think it is unnecessary., Conclusions: The use of CAM by patients with maintenance HD was relatively frequent. Of these, most used CHM, of which are shown to the trend into routine HD care is inevitable by high coverage and utilization in Taiwanese national health insurance system. These findings indicate that it is important for health care providers working in dialysis to assess CAM use., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee at Kaohsiung Chang Gung Memorial Hospital (registration number 202200422B0) as well as each research facility. This study was performed in accordance with the tenets set forth in the Declaration of Helsinki. All enrolled patients provided informed written consent prior to participation. Consent for publication Not Applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C., Methods: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset., Results: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors., Conclusion: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)-induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF-induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti-proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR-targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

A 65-year-old man with end-stage renal failure, severe aortic stenosis, and triple vessel coronary artery disease was admitted for percutaneous coronary intervention to the left anterior descending artery prior to transcatheter aortic valve replacement.

To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities., 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 B.V. All rights reserved.)

This retrospective study investigated the incidence, medication use, and outcomes in pediatric autosomal-dominant polycystic kidney disease (ADPKD) using Taiwan's National Health Insurance Research Database (NHIRD). A 1:4 matched control group of individuals included in the NHIRD during the same period was used for comparative analyses. A total of 621 pediatric patients were identified from 2009 to 2019 (mean age, 9.51 ± 6.43 years), and ADPKD incidence ranged from 2.32 to 4.45 per 100,000 individuals (cumulative incidence, 1.26-1.57%). The incidence of newly developed hypertension, anti-hypertensive agent use, nephrolithiasis, and proteinuria were significantly higher in the ADPKD group than the non-ADPKD group (0.7 vs. 0.04, 2.26 vs. 0.30, 0.4 vs. 0.02, and 0.73 vs. 0.05 per 100 person-years, respectively). The adjusted hazard ratios for developing hypertension, proteinuria, nephrolithiasis and anti-hypertensive agent use in cases of newly-diagnosed pediatric ADPKD were 12.36 (95% CI 4.92-31.0), 13.49 (95% CI 5.23-34.79), 13.17 (95% CI 2.48-69.98), and 6.38 (95% CI 4.12-9.89), respectively. The incidence of congenital cardiac defects, hematuria, urinary tract infections, gastrointestinal diverticulosis, dyslipidemia, and hyperuricemia were also higher in the ADPKD group. Our study offers valuable insights into the epidemiology of pediatric ADPKD in Taiwan and could help in formulating guidelines for its appropriate management., (© 2024. The Author(s).)

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention., Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant., Results: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours., Conclusions: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723., Competing Interests: L.T. is on the Astra Zeneca international advisory board of management of adverse events with the new antibody drug conjugate T-DXd in Asian patients with metastatic breast cancer, Roche Singapore immunotherapy in early stage NSCLC patient journey advisory board. L.T. has received a Philips speaker honorarium in kind and a Siemens Healthineers speaker honorarium. Y.K.K. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, and Novartis (via institution); consulting fees from Abbott Vascular, Medtronic, Novartis, and Peijia Medical; and speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Amgen, Novartis, Astra Zeneca, Microport, Terumo, and Omnicare. Y.K.K. is also cofounder and owns equity in Trisail, for which OrbusNeich is an investor. D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca and Merck Sharp & Dohme Corp. C.Y.C. has received speaker fees from Novartis and consultancy fees from Boston Scientific and Philips. The other authors report no conflicts.

Biomedical information retrieval for diagnosis, treatment and prognosis has been studied for a long time. In particular, image recognition using deep learning has been shown to be very effective for cancers and diseases. In these fields, scaphoid fracture recognition is a hot topic because the appearance of scaphoid fractures is not easy to detect. Although there have been a number of recent studies on this topic, no studies focused their attention on surgical treatment recommendations and nonsurgical prognosis status classification. Indeed, a successful treatment recommendation will assist the doctor in selecting an effective treatment, and the prognosis status classification will help a radiologist recognize the image more efficiently. For these purposes, in this paper, we propose potential solutions through a comprehensive empirical study assessing the effectiveness of recent deep learning techniques on surgical treatment recommendation and nonsurgical prognosis status classification. In the proposed system, the scaphoid is firstly segmented from an unknown X-ray image. Next, for surgical treatment recommendation, the fractures are further filtered and recognized. According to the recognition result, the surgical treatment recommendation is generated. Finally, even without sufficient fracture information, the doctor can still make an effective decision to opt for surgery or not. Moreover, for nonsurgical patients, the current prognosis status of avascular necrosis, non-union and union can be classified. The related experimental results made using a real dataset reveal that the surgical treatment recommendation reached 80% and 86% in accuracy and AUC (Area Under the Curve), respectively, while the nonsurgical prognosis status classification reached 91% and 96%, respectively. Further, the methods using transfer learning and data augmentation can bring out obvious improvements, which, on average, reached 21.9%, 28.9% and 5.6%, 7.8% for surgical treatment recommendations and nonsurgical prognosis image classification, respectively. Based on the experimental results, the recommended methods in this paper are DenseNet169 and ResNet50 for surgical treatment recommendation and nonsurgical prognosis status classification, respectively. We believe that this paper can provide an important reference for future research on surgical treatment recommendation and nonsurgical prognosis classification for scaphoid fractures.

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (T g ) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below T g of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with T g of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2-12 years., Methods and results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33-321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10-129.81) were independent risk factors for AR progression after closure., Conclusions: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health. Thus, salt reduction initiatives have been initiated since 2010, and two series of strategies have been launched. However, there are issues on its delivery and outreach to the target audience. Further, strategies targeting out of home sectors are yet to be emphasized. Our recent findings on the perceptions, barriers and enablers towards salt reduction among various stakeholders including policy-makers, food industries, food operators, consumers and schools showed that eating outside of the home contributed to high salt intake. Foods sold outside the home generally contain a high amount of salt. Thus, this supplementary document is being proposed to strengthen the Salt Reduction Strategy to Prevent and Control Non-communicable Diseases (NCDs) for Malaysia 2021-2025 by focussing on the strategy for the out-of-home sectors. In this supplementary document, the Monitoring, Awareness and Product (M-A-P) strategies being used by the Ministry of Health (MOH) are adopted with a defined outline of the plan of action and indicators to ensure that targets could be achieved. The strategies will involve inter-sectoral and multi-disciplinary approaches, including monitoring of salt intake and educating consumers, strengthening the current enforcement of legislation on salt/sodium labelling and promoting research on reformulation. Other strategies included in this supplementary document included reformulation through proposing maximum salt targets for 14 food categories. It is hoped that this supplementary document could strengthen the current the Salt Reduction Strategy to Prevent and Control NCDs for Malaysia 2021-2025 particularly, for the out-of-home sector, to achieve a reduction in mean salt intake of the population to 6.0 g per day by 2025., (© 2024. The Author(s).)

Background: Complementary and alternative medicine (CAM) is frequently used in the general population, yet only limited data are available regarding the prevalence of these medications in patients with chronic kidney disease (CKD). Hence, our study aimed to explore the prevalence and types of CAM in Taiwanese patients with CKD., Methods: A cross-sectional questionnaire survey was conducted by face-to-face interview of 275 pre-dialysis patients without dialysis treatment or kidney transplant at an outpatient nephrology clinic in Taiwan from March 2021 to June 2023. The study outcomes were the prevalence of CAM, CAM types, reasons for using CAM, and sources of information about CAM., Results: Overall, 128 patients (46.5%) were using CAM, but no significant differences from non-CAM users in the various CKD stages (p = 0.156) were found. CAM usage was high in the age range of 20-60 years and duration of CKD ≤ 5 years (p < 0.05). The most commonly used type of CAM was nutritional approaches (79.7%), followed by other complementary health approaches (26.6%). The most commonly utilized modalities of CAM were vitamins and minerals (38.3%), and only 27.1% of patients disclosed their CAM use to their physicians. The most common sources of information about CAM were family and friends, cited by 66% of the participants. Health promotion and a proactive attitude were reported by 40% of users as the reasons for using CAM., Conclusions: The present study provides data on the CAM usage among CKD patients and adds to the increasing evidence on CAM use. Because some of these practices have safety concerns, better education from healthcare providers on the risks and benefits of CAM therapy is needed by CKD patients., (© 2024. The Author(s).)

Purpose To develop a new coronary CT angiography (CCTA)-based index, α×LL/MLD 4 , that considers lesion entrance angle (α) in addition to lesion length (LL) and minimal lumen diameter (MLD) and to evaluate its efficacy in predicting hemodynamically significant coronary stenosis compared with invasive coronary angiography (ICA)-derived fractional flow reserve (FFR). Materials and Methods This prospective study enrolled participants (September 2016-March 2020) from two centers who underwent CCTA followed by ICA (ClinicalTrials.gov identifier: NCT03054324). CCTA images were processed semiautomatically to measure LL, MLD, and α for calculating α×LL/MLD 4 . Diagnostic performance and accuracy of α×LL/MLD 4 and LL/MLD 4 in detecting hemodynamically significant coronary stenosis were compared against the reference standard (invasive FFR ≤ 0.80). Results In total, 133 participants (mean age, 63 years ± 9 [SD]; 99 [74%] men) with 210 stenosed coronary arteries were analyzed. Median α×LL/MLD 4 was 54.0 degree/mm 3 (IQR, 25.3-128.7) in participants with invasive FFR of 0.80 or less and 6.7 degree/mm 3 (IQR, 3.3-12.8) in participants with invasive FFR of more than 0.80 ( P < .001). The per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for discriminating ischemic lesions were 86.2%, 83.1%, 88.4%, 84.1%, and 87.7% for α×LL/MLD 4 and 80.5%, 66.3%, 90.9%, 84.3%, and 78.6% for LL/MLD 4 , respectively. Area under the receiver operating characteristic curve for discriminating hemodynamically significant stenosis was 0.93 for α×LL/MLD 4 , which was significantly greater than the values of 0.84 for LL/MLD 4 and 0.63 for diameter stenosis (both P < .001). Conclusion The new morphologic index, α×LL/MLD 4 , incorporating lesion entrance angle achieved higher diagnostic performance in detecting hemodynamically significant lesions compared with diameter stenosis and LL/MLD 4 . Keywords: CT Angiography, Cardiac, Coronary Arteries, Ischemia, Infarction, Technology Assessment Clinical trial registration no. NCT03054324 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Fairbairn and Nørgaard in this issue.

Patients with chronic kidney disease (CKD) have traditionally been excluded from randomized trials. We aimed to compare percutaneous coronary intervention versus conservative management, and early intervention (EI; within 24 hours of admission) versus delayed intervention (DI; after 24 to 72 hours of admission) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and concomitant CKD. An electronic literature search was performed to search for studies comparing invasive management to conservative management or EI versus DI in patients with NSTEMI with CKD. The primary outcome was all-cause mortality; secondary outcomes were acute kidney injury (AKI) or dialysis, major bleeding, and recurrent MI. Hazard ratios (HRs) for the primary outcome and odds ratios for secondary outcomes were pooled in random-effects meta-analyses. Eleven studies (140,544 patients) were analyzed. Invasive management was associated with lower mortality than conservative management (HR 0.62, 95% confidence interval 0.57 to 0.67, p <0.001, I 2  = 47%), with consistent benefit across all CKD stages, except CKD 5. There was no significant mortality difference between EI and DI, but subgroup analyses showed significant benefit for EI in stage 1 to 2 CKD (HR 0.75, 95% confidence interval 0.58 to 0.97, p = 0.03, I 2  = 0%), with no significant difference in stage 3 and 4 to 5 CKD. Invasive strategy was associated with higher odds of AKI or dialysis and major bleeding, but lower odds of recurrent MI compared with conservative management. In conclusion, in patients with NSTEMI and CKD, an invasive strategy is associated with significant mortality benefit over conservative management in most patients with CKD, but at the expense of higher risk of AKI and bleeding. EI appears to benefit those with early stages of CKD. Trial Registration: PROSPERO CRD42023405491., Competing Interests: Declaration of Competing Interest Dr. Yap received speakers honorarium from Abbott, Biosensors, Biotronik, Boston Scientific, GE Healthcare, J&J, Kaneka, Medtronic, and Terumo. Dr. Keh received educational grants from Boston Scientific, Abbott, and Terumo. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes., Methods: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups., Results: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD., Conclusion: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer's disease, Parkinson's disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases., Competing Interests: The authors have no conflicts of interest to disclose.

Introduction: Quantifying disparities in social determinants of health between people with HIV and the total population could help address health inequities, and ensure health and well-being among people with HIV in the U.S., but estimates are lacking., Methods: Several representative data sources were used to assess differences in social determinants of health between adults with diagnosed HIV (Centers for Disease Control and Prevention Medical Monitoring Project) and the total adult population (U.S. Census Bureau's decennial census, American Community Survey, Household Pulse Survey, the Current Population Survey Annual Social and Economic Supplements; the Department of Housing and Urban Development's point-in-time estimates of homelessness; and the Bureau of Justice Statistics). The differences were quantified using standardized prevalence differences and standardized prevalence ratios, adjusting for differences in age, race/ethnicity, and birth sex between people with HIV and the total U.S. population., Results: Overall, 35.6% of people with HIV were living in a household with an income at or below the federal poverty level, and 8.1% recently experienced homelessness. Additionally, 42.9% had Medicaid and 27.6% had Medicare; 39.7% were living with a disability. Over half (52.3%) lived in large central metropolitan counties and 20.6% spoke English less than very well based on survey responses. After adjustment, poverty (standardized prevalence difference=25.1%, standardized prevalence ratio=3.5), homelessness (standardized prevalence difference=8.5%, standardized prevalence ratio=43.5), coverage through Medicaid (standardized prevalence difference=29.5%, standardized prevalence ratio=3.0) or Medicare (standardized prevalence difference=7.8%), and disability (standardized prevalence difference=30.3%, standardized prevalence ratio=3.0) were higher among people with HIV than the total U.S. population. The percentage of people with HIV living in large central metropolitan counties (standardized prevalence difference=13.4%) or who were recently incarcerated (standardized prevalence ratio=5.9) was higher than the total U.S. population., Conclusions: These findings provide a baseline for assessing national-level disparities in social determinants of health between people with HIV and the total U.S. population, and it can be used as a model to assess local disparities. Addressing social determinants of health is essential for achieving health equity, requiring a multipronged approach with interventions at the provider, facility, and policy levels.

Myo-Inositol (MI) has been shown to alleviate aging in Caenorhabditis (C). elegans. However, the mechanism by which MI alleviates aging remains unclear. In this study, we investigate whether MI can modulate the PI3K so as to attenuate the insulin/IGF-1 signaling (IIS) pathway and exert the longevity effect. The wild-type C. elegans and two mutants of AKT-1 and DAF-16 were used to explore the mechanism of MI so as to extend the lifespan, as well as to improve the health indexes of pharyngeal pumping and body bend, and an aging marker of autofluorescence in the C. elegans . We confirmed that MI could significantly extend the lifespan of C. elegans . MI also ameliorated the pharyngeal pumping and body bend and decreased autofluorescence. We further adopted the approach to reveal the loss-of-function mutants to find the signaling mechanism of MI. The functions of the lifespan-extending, health-improving, and autofluorescence-decreasing effects of MI disappeared in the AKT-1 and DAF-16 mutants. MI could also induce the nuclear localization of the DAF-16. Importantly, we found that MI could dramatically inhibit the phosphoinositide 3-kinase (PI3K) activity in a dose-dependent manner with an IC50 of 90.2 μM for the p110α isoform of the PI3K and 21.7 μM for the p110β. In addition, the downregulation of the PI3K expression and the inhibition of the AKT phosphorylation by MI was also obtained. All these results demonstrate that MI can inhibit the PI3K activity and downregulate the PI3K expression, and the attenuation of the IIS pathway plays a crucial role for MI in alleviating aging in C. elegans .

Background and Objectives: We compared real-world clinical outcomes of patients receiving intravascular lithotripsy (IVL) versus rotational atherectomy (RA) for heavily calcified coronary lesions., Methods: Fifty-three patients who received IVL from January 2017 to July 2020 were retrospectively compared to 271 patients who received RA from January 2017 to December 2018. Primary endpoints were in-hospital and 30-day major adverse cardiovascular events (MACE)., Results: IVL patients had a higher prevalence of acute coronary syndrome (56.6% vs 24.4, p<0.001), multivessel disease (96.2% vs 73.3%, p<0.001) and emergency procedures (17.0% vs 2.2%, p<0.001) compared to RA. In-hospital MACE (11.3% vs 5.9%, p=0.152), MI (7.5% vs 3.3%, p=0.152), and mortality (5.7% vs 3.0%, p=0.319) were not statistically significant. 30-day MACE was higher in the IVL cohort vs RA (17.0% vs 7.4%, p=0.035). Propensity score adjusted regression using IVL was also performed on in-hospital MACE (odds ratio [OR], 1.677; 95% confidence interval [CI], 0.588-4.779) and 30-day MACE (OR, 1.910; 95% CI, 0.774-4.718)., Conclusions: These findings represent our initial IVL experience in a high-risk, real-world cohort. Although the event rate in the IVL arm was numerically higher compared to RA, the small numbers and retrospective nature of this study preclude definitive conclusions. These clinical outcomes are likely to improve with greater experience and better case selection, allowing IVL to effectively treat complex calcified coronary lesions., Competing Interests: Dr Yeo Khung Keong has received research funding from Medtronic, Boston Scientific, Amgen, Astra Zeneca, Shockwave Medical (all significant, via institution); Consulting or honoraria fees (all modest) from Medtronic, Boston Scientific, Abbott Vascular, Amgen, Bayer, Novartis; Speaker or Proctor fees from Abbott Vascular, Boston Scientific, Medtronic, Philips, Shockwave Medical, Terumo, Alvimedica, Menarini, Astra Zeneca, Amgen, and Bayer. Dr Chin Chee Yang has received honoraria from Boston Scientific, Abbott Vascular, Medtronic, Philips, Terumo, and Alvimedica. Dr Yap Jonathan has received honoraria speaker fees (all modest) from Johnson & Johnson, and Terumo. The other authors have no financial conflict of interest., (Copyright © 2022. The Korean Society of Cardiology.)

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood mental disorder with undetermined pathophysiological mechanisms. The gut microbiota and immunological dysfunction may influence brain functions and social behaviours. In the current study, we aimed to explore the correlation of gut microbiome imbalance and inflammation in the pathophysiology of ADHD. Forty-one children with ADHD and thirty-nine healthy-control (HC) individuals were recruited. Faecal samples from all participants were collected and submitted for 16 S rRNA V3-V4 amplicon microbiome sequencing analysis. The plasma levels of 10 cytokines, including TNF-α, IL-6, IL-1β, IL-2, IL-10, IL-13, IL-17A, IFN-α2, IFN-γ, and MCP-1, were determined using a custom-made sandwich enzyme-linked immunosorbent assay (ELISA) developed by Luminex Flowmetrix. There was no significant difference between the ADHD and HC groups in species diversity in the faeces, as determined with α-diversity and β-diversity analysis. In the ADHD group, three differentially abundant taxonomic clades at the genus level were observed, namely Agathobacter, Anaerostipes, and Lachnospiraceae. Top differentially abundant bacteria and representative biological pathways were identified in children with ADHD using linear discriminant analysis (LDA) effect size (LEfSe), and the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis, respectively. The plasma levels of TNF-α were significantly lower in children with ADHD than in HCs. Within the ADHD group, the levels of TNF-α were negatively correlated with ADHD symptoms and diversity of the gut microbiome. Our study provides new insights into the association between gut microbiome dysbiosis and immune dysregulation, which may contribute to the pathophysiology of ADHD., (© 2022. The Author(s).)

Understanding crystallization behaviors is of utmost importance for developing robust amorphous pharmaceutical solids. Herein, the crystal growth behaviors of amorphous anti-inflammatory drug nimesulide (NIME) are systemically investigated in the glassy and supercooled liquid state as a function of temperature. A sudden over-tenfold increase is observed in the bulk crystal growth of NIME on cooling below its glass transition temperature (T g ). This fast growth behavior is known as a glass-to-crystal (GC) mode and has been reported in some molecular glasses. Fast surface crystal growth of NIME can persist up to T g  + 57°C with a weak jump in its growth rates at 30-40°C. In addition, surface crystal growth and GC growth of NIME exhibit an almost identical temperature dependence, supporting the view that GC growth is indeed a surface-facilitated process. Moreover, the bubble-induced fast crystal growth of NIME is observed in the interior of its supercooled liquid with approximately the same growth kinetics as surface crystal growth. These findings are relevant for a full understanding of the surface-related crystallization behaviors and physical stability of amorphous pharmaceutical formulations.

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Hsu, Lee, Liu, Tan, Chin, Chang and Yang.)

Acinetobacter baumannii is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic differences. Cells interconvert between the VIR-O and AV-T variants at high frequency under laboratory conditions, suggesting that the genetic mechanism underlying the phenotypic switch could be manipulated to attenuate virulence. Therefore, our group has focused on identifying and characterizing genes that regulate this switch, which led to the investigation of ABUW&#95;1132 ( 1132 ), a highly conserved gene predicted to encode a LysR-type transcriptional regulator. ABUW&#95;1132 was shown to be a global regulator as the expression of 74 genes was altered ≥ 2-fold in an 1132 deletion mutant. The 1132 deletion also resulted in a 16-fold decrease in VIR-O to AV-T switching, loss of 3-OH-C 12 -HSL secretion, and reduced surface-associated motility. Further, the deletion of 1132 in the AV-T background caused elevated capsule production, which increased colony opacity and altered the typical avirulent phenotype of translucent cells. These findings distinguish 1132 as a global regulatory gene and advance our understanding of A. baumannii 's opacity-virulence switch., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tierney, Chin, Weiss and Rather.)

In 2020 the COVID-19 pandemic caused millions to lose their jobs and, consequently, their employer-sponsored health insurance. Enacted in 2010, the Affordable Care Act (ACA) created safeguards for such events by expanding Medicaid coverage and establishing Marketplaces through which people could purchase health insurance. Using a novel national data set with information on ACA-compliant individual insurance plans, we found large increases in Marketplace enrollment in 2020 compared with 2019 but with varying percentage increases and spending risk implications across states. States that did not expand Medicaid had enrollment and spending risk increases. States that expanded Medicaid but did not relax 2020 Marketplace enrollment criteria also had spending risk increases. In contrast, states that expanded Medicaid and relaxed 2020 enrollment criteria experienced enrollment increases without spending risk changes. The findings are reassuring with respect to the ability of Marketplaces to buffer employment shocks, but they also provide cautionary signals that risks and premiums could begin to rise either in the absence of Medicaid expansion or when Marketplace enrollment is constrained.

The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFR AM ) to diagnose ischemic coronary lesions. Patients with suspected or known coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFR AM was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFR B ) and invasive ICA-based FFR. FFR AM , FFR B , and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30-83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFR AM and 87, 88, 86, 83, and 90% for FFR B . The area under the receiver operating characteristics curve for FFR AM (0.89 and 0.87) and FFR B (0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all p < 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFR AM was much shorter than FFR B (2.2 ± 0.9 min vs . 48 ± 36 min, excluding image acquisition and segmentation). FFR AM calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFR B , with a significantly shorter computational time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Han, Tan, Chai, Fam, Teo, Chin, Ong, Low, Chandola, Leng, Huang, Allen, Baskaran, Kassab, Low, Chan, Chan, Loh, Wong, Tan, Chua, Lim and Zhong.)

Invasive fractional flow reserve (FFR) is recommended to guide stent deployment. We previously introduced a non-invasive FFR calculation (FFR B ) based on computed tomography coronary angiography (CTCA) with reduced-order computational fluid dynamics (CFD) and resistance boundary conditions. Current study aimed to assess the feasibility and accuracy of FFR B for predicting coronary hemodynamics before and after stenting, with invasive FFR as the reference. Twenty-five patients who had undergone CTCA were prospectively enrolled before invasive coronary angiography (ICA) and FFR-guided percutaneous coronary intervention (PCI) on 30 coronary vessels. Using reduced-order CFD with novel boundary conditions on three-dimensional (3D) patient-specific anatomic models reconstructed from CTCA, we calculated FFR B before and after virtual stenting. The latter simulated PCI by clipping stenotic segments from the 3D coronary models and replacing them with segments to mimic the deployed coronary stents. Pre- and post-virtual stenting FFR B were compared with FFR measured pre- and post-PCI by investigators blinded to FFR B results. Among 30 coronary lesions, pre-stenting FFR B (mean 0.69 ± 0.12) and FFR (mean 0.67 ± 0.13) exhibited good correlation ( r = 0.86, p < 0.001) and agreement [mean difference 0.024, 95% limits of agreement (LoA): -0.11, 0.15]. Similarly, post-stenting FFR B (mean 0.84 ± 0.10) and FFR (mean 0.86 ± 0.08) exhibited fair correlation ( r = 0.50, p < 0.001) and good agreement (mean difference 0.024, 95% LoA: -0.20, 0.16). The accuracy of FFR B for identifying post-stenting ischemic lesions (FFR ≤ 0.8) (residual ischemia) was 87% (sensitivity 80%, specificity 88%). Our novel FFR B , based on CTCA with reduced-order CFD and resistance boundary conditions, accurately predicts the hemodynamic effects of stenting which may serve as a tool in PCI planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chandola, Zhang, Tan, Chai, Teo, Allen, Low, Huang, Leng, Fam, Chin, Kassab, Low, Tan, Chua, Lim and Zhong.)

Background: Adenosine triphosphate (ATP) has been predominantly used in the Asia-Pacific region for stress perfusion cardiovascular magnetic resonance (CMR). We evaluated the prognosis of patients stressed using ATP, for which there are no current data., Methods: We performed a retrospective longitudinal study from January 2016 to December 2020 and included 208 subjects with suspected obstructive coronary artery disease (CAD) who underwent ATP stress perfusion CMR. An inducible stress perfusion defect was defined as a subendocardial dark rim involving ≥ 1.5 segments that persisted for ≥ 6 beats during stress but not at rest. The primary outcome measure was a composite of major adverse cardiovascular events (MACE) including (1) cardiac death, (2) nonfatal myocardial infarction, (3) cardiac hospitalization, (4) late coronary revascularization. We compared outcomes in patients with and without perfusion defect using Kaplan-Meier and log rank tests. Significant predictors of MACE were identified using multivariable Cox regression analysis., Results: Median follow-up was 3.3 years. Patients with no stress perfusion defect had a lower incidence of MACE (p < 0.001), including lower cardiac hospitalization (p = 0.004), late coronary revascularization (p = 0.001) and cardiac death (p = 0.003). Significant independent predictors for MACE were stress induced perfusion defect (p < 0.001, hazard ratio [HR] = 3.63), lower left ventricular ejection fractino (LVEF) (p < 0.001, HR = 0.96) and infarct detected by late gadolinium enhancement (LGE) (p = 0.001, HR = 2.92)., Conclusion: Perfusion defects on ATP stress are predictive of MACE which is driven primarily by cardiac hospitalization, late coronary revascularization and cardiac death. Significant independent predictors of MACE were stress induced perfusion defect, lower LVEF and infarct detected by LGE.

The outer membrane protects Gram-negative bacteria from the host environment. Lipopolysaccharide (LPS), a major outer membrane constituent, has distinct components (lipid A, core, O-antigen) generated by specialized pathways. In this study, we describe the surprising convergence of these pathways through FlmX, an uncharacterized protein in the intracellular pathogen Francisella. FlmX is in the flippase family, which includes proteins that traffic lipid-linked envelope components across membranes. flmX deficiency causes defects in lipid A modification, core remodeling, and O-antigen addition. We find that an F. tularensis mutant lacking flmX is >1,000,000-fold attenuated. Furthermore, FlmX is required to resist the innate antimicrobial LL-37 and the antibiotic polymyxin. Given FlmX's central role in LPS modification and its conservation in intracellular pathogens Brucella, Coxiella, and Legionella, FlmX may represent a novel drug target whose inhibition could cripple bacterial virulence and sensitize bacteria to innate antimicrobials and antibiotics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A dramatic growth in the prevalence of chronic wounds due to diabetes has represented serious global health care and economic issues. Hence, there is an imperative need to develop an effective and affordable wound dressing for chronic wounds. Recent research has featured the potential of bioactive compound gallic acid (GA) in the context of wound recovery due to their safety and comparatively low cost. However, there is a scarcity of research that focuses on formulating GA into a stable and functional hydrocolloid film dressing. Thus, this present study aimed to formulate and characterise GA-loaded alginate-based hydrocolloid film dressing which is potentially used as low to medium suppurating chronic wound treatment. Methods: The hydrocolloid composite films were pre-formulated by blending sodium alginate (SA) with different combinations of polymers. The hydrocolloid films were developed using solvent-casting method and the most satisfactory film formulation was further incorporated with various GA concentrations (0.1%, 0.5% and 1%). The drug-loaded films were then characterised for their physicochemical properties to assess their potential use as drug delivery systems for chronic wound treatment. Results: In the pre-formulation studies, sodium alginate-pectin (SA-PC) based hydrocolloid film was found to be the most satisfactory, for being homogenous and retaining smoothness on surface along with satisfactory film flexibility. The SA-PC film was chosen for further loading with GA in 0.1%, 0.5% and 1%. The characterisation studies revealed that all GA-loaded films possess superior wound dressing properties of acidic pH range (3.97-4.04), moderate viscosity (1600 mPa-s-3198 mPa-s), optimal  moisture vapor transmission rate (1195 g/m 2 /day, 1237g/m 2/ day and 1112 g/m 2 /day), slower moisture absorption and film expansion rate and no chemical interaction between the GA and polymers under FTIR analysis. Conclusion: An SA-PC hydrocolloid film incorporated with gallic acid as a potentially applicable wound dressing for low to medium suppurating chronic wounds was successfully developed., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Gan JE and Chin CY.)

Facing the COVID-19 pandemic, Taiwan demonstrated resilience at the initial stage of epidemic prevention, and effectively slowed down its spread. This study aims to document public epidemic awareness of COVID-19 in Taiwan through collecting social media- and Internet-based data, and provide valuable experience of Taiwan's response to COVID-19, involving citizens, news media, and the government, to aid the public in overcoming COVID-19, or infectious diseases that may emerge in the future. The volume of Google searches related to COVID-19 and face masks was regarded as an indicator of public epidemic awareness in the study. A time-series analysis was used to explore the relationships among public epidemic awareness and other COVID-19 relevant variables, which were collected based on big data analysis. Additionally, the content analysis was adopted to analyze the transmission of different types of fear information related to COVID-19 and their effects on the public. Our results indicate that public epidemic awareness was significantly correlated with the number of confirmed cases in Taiwan and the number of news reports on COVID-19 (correlation coefficient: .33-.56). Additionally, the findings from the content analysis suggested that the fear of the loss of control best explains why panic behavior occurs among the public. When confronting the highly infectious COVID-19, public epidemic awareness is vital. While fear is an inevitable result when an emerging infectious disease occurs, the government can convert resistance into assistance by understanding why fear arises and which fear factors cause excessive public panic. Moreover, in the digitalization era, online and social media activities could reflect public epidemic awareness that can e harnessed for epidemic control., Competing Interests: The funder of Big Data Co., Ltd. provided financial support in the form of salaries for the author, CL. It offered a part of the study’s research materials. The support does not alter our adherence to PLOS ONE policies on sharing data and materials.

This study applies an empirical analysis to examine whether supply chain disruption is caused by the outbreak of the coronavirus disease (COVID-19) that was first reported in Wuhan, China, on December 31, 2019. The study's findings indicate a link between the COVID-19 outbreak and the disruption of logistics and supply chains along with negative cumulative abnormal returns within Taiwanese firms manufacturing products in China and marketing them globally. This is the first study to examine the outbreak of the COVID-19 and the disruption of the supply chain and its effect on the stock market. The empirical results provide insights for business management in reconsidering their global supply chain strategies for the risk of disruption caused by similar epidemics occurs in the future., (© 2020 Elsevier B.V. All rights reserved.)

In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive, life-threatening lung disease with increasing prevalence and incidence worldwide. Increasing evidence suggests that lung microbiomes might play a physiological role in acute exacerbations of COPD. The objective of this study was to characterize the association of the microbiota and exacerbation risk or airflow limitation in stable COPD patients., Methods: The sputum microbiota from 78 COPD outpatients during periods of clinical stability was investigated using 16S rRNA V3-V4 amplicon sequencing. The microbiome profiles were compared between patients with different risks of exacerbation, i.e., the low risk exacerbator (LRE) or high risk exacerbator (HRE) groups, and with different airflow limitation severity, i.e., mild to moderate (FEV1 ≥ 50; PFT I) or severe to very severe (FEV1 < 50; PFT II)., Results: The bacterial diversity (Chao1 and observed OTUs) was significantly decreased in the HRE group compared to that in the LRE group. The top 3 dominant phyla in sputum were Firmicutes, Actinobacteria, and Proteobacteria, which were similar in the HRE and LRE groups. At the genus level, compared to that in the LRE group (41.24%), the proportion of Streptococcus was slightly decreased in the HRE group (28.68%) (p = 0.007). However, the bacterial diversity and the proportion of dominant bacteria at the phylum and genus levels were similar between the PFT I and PFT II groups. Furthermore, the relative abundances of Gemella morbillorum, Prevotella histicola, and Streptococcus gordonii were decreased in the HRE group compared to those in the LRE group according to linear discriminant analysis effect size (LEfSe). Microbiome network analysis suggested altered bacterial cooperative regulation in different exacerbation phenotypes. The proportions of Proteobacteria and Neisseria were negatively correlated with the FEV1/FVC value. According to functional prediction of sputum bacterial communities through Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis, genes involved in lipopolysaccharide biosynthesis and energy metabolism were enriched in the HRE group., Conclusion: The present study revealed that the sputum microbiome changed in COPD patients with different risks of exacerbation. Additionally, the bacterial cooperative networks were altered in the HRE patients and may contribute to disease exacerbation. Our results provide evidence that sputum microbiome community dysbiosis is associated with different COPD phenotypes, and we hope that by understanding the lung microbiome, a potentially modifiable clinical factor, further targets for improved COPD therapies during the clinically stable state may be elucidated.

Background: Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard., Methods: In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study., Results: In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ 2 for the diagnosis of FFR-positive increased from 7.6 to 55.9; P < 0.001) and excellent performance [c-statistic area under the curve 0.97 (95% CI: 0.94-1.00)] in discriminating between FFR-normal and FFR-positive patients., Conclusion: The study demonstrates the clinical potential of using in-scanner multiparametric ExCMR to accurately diagnose CAD., Trial Registration: ClinicalTrials.gov, NCT03217227, Registered 11 July 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03217227?id=NCT03217227&draw=2&rank=1&load=cart.

Competing Interests: Funding Support and Author Disclosures Dr. Yeo has received research funding from Medtronic, Boston Scientific, Amgen, AstraZeneca, Shockwave Medical (all significant, via institution); has received consulting or honoraria fees (all modest) from Medtronic, Boston Scientific, Abbott Vascular, Amgen, Bayer, and Novartis; and has received speaker or proctor fees from Abbott Vascular, Boston Scientific, Medtronic, Philips, Shockwave Medical, Alvimedica, Menarini, AstraZeneca, Amgen, and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Exposure to fine particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM 2. 5 ) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. As reported recently, PM 2. 5 exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM 2. 5 alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM 2. 5 exposure combined with Streptococcus pneumonia infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3-V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher's diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM 2. 5 or pneumococcus when compared with the control group. The genera Streptococcus , Prevotella , Leptotrichia , and Granulicatella were remarkably increased in mice exposed to PM 2. 5 combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM 2. 5 and pneumococcus than that in mouse groups exposed to either PM 2. 5 or pneumococcal infection alone. Our results demonstrate that PM 2. 5 alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis., (Copyright © 2020 Chen, Li, Lin, Huang, Lin, Chin, Lai, Chiu, Yang and Lai.)

We sought to compare the vaginal microbiota profiles of Taiwanese women with severe preeclampsia (SPE) and normotensive control pregnancies. In a discovery cohort, vaginal swab samples and paired blood specimens were simultaneously obtained at the time of caesarean delivery from 30 women with SPE and 30 controls. The composition of vaginal microbiota was characterised by 16S ribosomal RNA gene sequencing of the V3-V4 region. Results were subsequently validated by real-time qPCR. We sought confirmation of our findings in an expanded cohort consisting of 58 women with SPE and 55 controls. In both the discovery and confirmation cohorts, women with SPE had higher relative abundance of Prevotella bivia in their vaginal microbial community (P = 0.006 and 0.011, respectively). Plasma levels of tumour necrosis factor alpha (TNF-α) were higher when compared with controls (P = 0.031) in the confirmation cohort. Three variables (vaginal Prevotella bivia, plasma TNF-α, and body mass index [BMI]) were included in a prediction panel for SPE. Of these, BMI was the most predictive variable. The area under the curve (AUC) of predicted probability values for the three-variable panel revealed that it can discriminate between SPE and normotensive pregnancies with good accuracy (AUC = 0.797, P < 0.001). We conclude that enrichment of Prevotella bivia in vaginal microbiota, which is tightly regulated by BMI, may be involved in the pathogenesis of SPE.

We describe a novel genetic mechanism in which tandem amplification of a plasmid-borne integron regulates virulence, opacity variation, and global gene expression by altering levels of a putative small RNA (sRNA) in Acinetobacter baumannii AB5075. Copy number of this amplified locus correlated with the rate of switching between virulent opaque (VIR-O) and avirulent translucent (AV-T) cells. We found that prototypical VIR-O colonies, which exhibit high levels of switching and visible sectoring with AV-T cells by 24 h of growth, harbor two copies of this locus. However, a subset of opaque colonies that did not form AV-T sectors within 24 h were found to harbor only one copy. The colonies with decreased sectoring to AV-T were designated low-switching opaque (LSO) variants and were found to exhibit a 3-log decrease in switching relative to that of the VIR-O. Overexpression studies revealed that the element regulating switching was localized to the 5' end of the aadB gene within the amplified locus. Northern blotting indicated that an sRNA of approximately 300 nucleotides (nt) is encoded in this region and is likely responsible for regulating switching to AV-T. Copy number of the ∼300-nt sRNA was also found to affect virulence, as the LSO variant exhibited decreased virulence during murine lung infections. Global transcriptional profiling revealed that >100 genes were differentially expressed between VIR-O and LSO variants, suggesting that the ∼300-nt sRNA may act as a global regulator. Several virulence genes exhibited decreased expression in LSO cells, potentially explaining their decreased virulence. IMPORTANCE Acinetobacter baumannii remains a leading cause of hospital-acquired infections. Widespread multidrug resistance in this species has prompted the WHO to name carbapenem-resistant A. baumannii as its top priority for research and development of new antibiotics. Many strains of A. baumannii undergo a high-frequency virulence switch, which is an attractive target for new therapeutics targeting this pathogen. This study reports a novel mechanism controlling the frequency of switching in strain AB5075. The rate of switching from the virulent opaque (VIR-O) to the avirulent translucent (AV-T) variant is positively influenced by the copy number of an antibiotic resistance locus encoded on a plasmid-borne composite integron. Our data suggest that this locus encodes a small RNA that regulates opacity switching. Low-switching opaque variants, which harbor a single copy of this locus, also exhibit decreased virulence. This study increases our understanding of this critical phenotypic switch, while also identifying potential targets for virulence-based A. baumannii treatments.

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 μM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFR B using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFR B computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFR B increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFR B decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFR B calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) ( r  = 0.92, P < 0.001). Positive association was observed between FFR B and MBP input values (mmHg) and negative association between FFR B and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFR B in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFR B ) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.

Background: Renal disease is prevalent in gouty patients and monosodium urate (MSU) crystal deposition in the kidney can be detected in some gouty nephropathy patients. MSU crystals can induce inflammatory events, we investigated the MSU-induced expression of intercellular adhesion molecule (ICAM)-1 on human renal mesangial cells (HRMCs) and the involved signal transduction mechanisms., Methods: The HRMCs cell line was purchased from ScienCell Research Laboratories. MSU crystals were made by dissolving uric acid in sodium hydroxide (NaOH) solution. The involvement of MAPKs, apoptosis-associated speck-like protein containing a CARD domain (ASC), and Toll-like receptor (TLR) was investigated using pharmacological inhibitors, transfection with short hairpin RNA (shRNA), or monoclonal antibodies. Protein expression was evaluated by Western blotting. The functional activity of ICAM-1 was evaluated with cell-cell adhesion assay and immunofluorescence analysis., Results: MSU stimulation increased expression of ICAM-1 and adhesion between HRMCs and human monocytic THP-1 cells. The interaction between HRMCs and THP-1 was suppressed by ICAM-1 neutralizing antibodies. MSU stimulation induced activation of mitogen-activated protein kinases, including c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK), but only p38 was responsible for MSU-induced expression of ICAM-1 and cell-cell adhesion. ASC also play a role in MSU-induced effects. Pretreatment with monoclonal antibodies against toll-like receptor (TLR)2 or TLR4 reduced MSU-induced ICAM-1 expression, cell-cell adhesion, p38 phosphorylation but the reduction of ASC activation is insignificant., Conclusion: The MSU induced ICAM-1 expression on HRMCs and cell-cell adhesion involved TLR2/4-p38-ICAM1 pathway and TLR2/4 independent ASC-p38-ICAM1 axis. These findings might partly explain the mechanisms underlying gouty nephropathy., (Copyright © 2018. Published by Elsevier B.V.)

Background: Complementary and alternative medicine (CAM) is becoming more common in medical practice, but little is known about the concurrent use of CAM and conventional treatment. Therefore, the aim was to investigate the types of CAM used and their prevalence in a regional patient cohort with breast cancer (BC)., Methods: BC patients were interviewed with a structured questionnaire survey on the use of CAM in southern Taiwan at an Integrative Breast Cancer Center (IBCC). The National Centre for Complementary and Integrative Health (NCCIH) classification was used to group responses. Over a period of 8 months, all patients receiving treatment for cancer at the IBCC were approached., Results: A total of 106 BC patients completed the survey (response rate: 79.7%). The prevalence of CAM use was 82.4%. Patients who were employed, were receiving radiotherapy and hormone therapy, and had cancer for a longer duration were more likely to use CAM ( P  < .05). Multivariate analysis identified employment as an independent predictor of CAM use (OR = 6.92; 95% CI = 1.33-36.15). Dietary supplementation (n = 69, 82.1%) was the type of CAM most frequently used, followed by exercise (n = 48, 57.1%) and traditional Chinese medicine (n = 29, 34.5%). The main reason for using CAM was to ameliorate the side effects of conventional therapies. Almost half (46.4%) of these CAM users did not disclose that they were using it in medical consultations with their physicians. Most chose to use CAM due to recommendations from family and friends., Conclusion: A large portion of BC patients at the IBCC undergoing anti-cancer treatment courses used CAM, but less than half discussed it with their physicians. Given the high prevalence of CAM, it would be justifiable to direct further resources toward this service so that cancer patients can benefit from a holistic approach to their treatment.

Improvements in next-generation sequencing technologies have resulted in dramatically reduced sequencing costs. This has led to an explosion of '-seq'-based methods, of which RNA sequencing (RNA-seq) for generating transcriptomic data is the most popular. By analysing global patterns of gene expression in organs/tissues/cells of interest or in response to chemical or environmental perturbations, researchers can better understand an organism's biology. Tools designed to work with large RNA-seq data sets enable analyses and visualizations to help generate hypotheses about a gene's function. We present here a user-friendly RNA-seq data exploration tool, called the 'eFP-Seq Browser', that shows the read map coverage of a gene of interest in each of the samples along with 'electronic fluorescent pictographic' (eFP) images that serve as visual representations of expression levels. The tool also summarizes the details of each RNA-seq experiment, providing links to archival databases and publications. It automatically computes the reads per kilobase per million reads mapped expression-level summaries and point biserial correlation scores to sort the samples based on a gene's expression level or by how dissimilar the read map profile is from a gene splice variant, to quickly identify samples with the strongest expression level or where alternative splicing might be occurring. Links to the Integrated Genome Browser desktop visualization tool allow researchers to visualize and explore the details of RNA-seq alignments summarized in eFP-Seq Browser as coverage graphs. We present four cases of use of the eFP-Seq Browser for ABI3, SR34, SR45a and U2AF65B, where we examine expression levels and identify alternative splicing. The URL for the browser is https://bar.utoronto.ca/eFP-Seq&#95;Browser/. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. Tool is at https://bar.utoronto.ca/eFP-Seq&#95;Browser/; RNA-seq data at https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq&#95;bam/ and https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq&#95;bam/Klepikova/. Code is available at https://github.com/BioAnalyticResource/eFP-Seq-Browser., (© 2019 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)