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Antimicrobial susceptibilities of 4973 Bacteroides spp. isolates recovered from various sources of patients from 12 countries (99.6% from European countries) in the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2007-2020, were investigated. The minimum inhibitory concentrations (MICs) of the isolates with six commonly used agents were determined using the agar dilution method. Among the isolates, 10 Bacteroides spp. were included: B. fragilis (n=3180, 64.0%) was encountered most frequently, followed by B. thetaiotaomicron (n=675) and B. ovatus (n=409). During the 14 years, the proportion of B. fragilis declined, but the proportion of non-fragilis Bacteroides spp. increased. More than 90% of the isolates tested were susceptible to piperacillin-tazobactam, meropenem and tigecycline. Significantly lower susceptibility rates to cefoxitin (P<0.001), clindamycin (P<0.001), piperacillin/tazobactam (P<0.001) and tigecycline (P=0.006) were observed among non-fragilis Bacteroides spp. isolates than among B. fragilis isolates. Moreover, the susceptibility rates to clindamycin (P=0.003) and tigecycline (P=0.044) decreased significantly among non-fragilis Bacteroides spp. over time. Clindamycin susceptibility rates >80% were found in Greece (100%), Sweden (86.3%) and the UK (80.7%), and the lowest susceptibility rates were found in the USA (42.9%) and Japan (53.9%). In conclusion, the susceptibility of Bacteroides spp. to commonly used antibiotics varied geographically. Empirical antibiotic therapy for suspected anaerobic infections with clindamycin and cefoxitin should be avoided due to high resistance rates. Piperacillin-tazobactam, meropenem, metronidazole and tigecycline could be considered favourable options for the treatment of infections caused by Bacteroides spp., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The prognosis of patients with colorectal cancer (CRC) mostly relies on the classic tumor node metastasis (TNM) staging classification. A more accurate and convenient prediction model would provide a better prognosis and assist in treatment. From May 2014 to December 2017, patients who underwent an operation for CRC were enrolled. The proposed feature ensemble vision transformer (FEViT) used ensemble classifiers to benefit the combinations of relevant colonoscopy features from the pretrained vision transformer and clinical features, including sex, age, family history of CRC, and tumor location, to establish the prognostic model. A total of 1729 colonoscopy images were enrolled in the current retrospective study. For the prediction of patient survival, FEViT achieved an accuracy of 94 % with an area under the receiver operating characteristic curve of 0.93, which was better than the TNM staging classification (90 %, 0.83) in the experiment. FEViT reduced the limited receptive field and gradient disappearance in the conventional convolutional neural network and was a relatively effective and efficient procedure. The promising accuracy of FEViT in modeling survival makes the prognosis of CRC patients more predictable and practical., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial and personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The use of nanodiamonds (NDs) and fluorescent nanodiamonds (FNDs) as nonallergenic biocompatible additives in incomplete Freund's adjuvant (IFA) to elicit immune responses in vivo was investigated. Methods: C57BL/6 mice were immunized with chicken egg ovalbumin (OVA) in IFA and also OVA-conjugated NDs (or OVA-conjugated FNDs) in IFA to produce antibodies. OVA-expressing E.G7 lymphoma cells and OVA-negative EL4 cells were inoculated in mice to induce tumor formation. Results: The new formulation significantly enhanced immune responses and thus disease resistance. It exhibited specific therapeutic activities, effectively inhibiting the growth of E.G7 tumor cells in mice over 35 days. Conclusion: The high biocompatibility and multiple functionalities of NDs/FNDs render them applicable as active and trackable vaccine adjuvants and antitumor agents.

This study aims to develop a 30 kHz/12 kW silicon carbide (SiC)/Si integrated hybrid power module (iHPM) for variable frequency drive applications, particularly industrial servo motor control, and, additionally, to theoretically and experimentally assess its dynamic characteristics and efficiency during operation. This iHPM integrates a brake circuit, a three-phase Si rectifier, and a three-phase SiC inverter within a single package to achieve a minimal current path. A space-vector pulse width modulation (SVPWM) scheme is used to control the inverter power switches. In order to reduce parasitic inductance and power loss, an inductance cancellation design is implemented in the Si rectifier and SiC inverter. The switching transients and their parasitic effects during a three-phase operation are assessed through an electromagnetic-circuit co-simulation model, by which the power loss and efficiency of the iHPM are estimated. The modeled parasitic inductance of the inverter is validated through inductance measurement, and the effectiveness of the simulated results in terms of switching transients and efficiency is verified using the experimental results of the double pulse test and open-loop inverter operation, respectively. In addition, the power loss and efficiency of the SiC MOSFET inverter are experimentally compared against those of a commercial Si IGBT inverter.

The efficient removal of gas bubbles is essential to reduce the reaction overpotential and improve the electrode stability in the hydrogen evolution reaction (HER). To address this challenge, the current study combines hydrophilic functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) with colloidal lithography to create superaerophobic electrode surfaces. The fabrication process involves the use of polystyrene (PS) beads with varying sizes (100, 200, and 500 nm) as hard templates and the electropolymerization of EDOTs with hydroxymethyl (EDOT-OH) and sulfonate (EDOT-SuNa) functional groups. The surface properties and HER performances of the electrodes are investigated. The electrode modified with poly(EDOT-SuNa) and 200 nm PS beads (SuNa/Ni/Au-200) exhibits the best hydrophilicity with a water contact angle of 37°. Moreover, the overpotential required at -10 mA cm -2 is substantially reduced from -388 mV (flat Ni/Au) to -273 mV (SuNa/Ni/Au-200). This approach is further applied to commercially available nickel foam electrodes, showing improved HER activity and electrode stability. These results highlight the potential for promoting catalytic efficiency by constructing a superaerophobic electrode surface.

Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated with LPS were demonstrated to cause survival loss and ROS generation, were recovered by Q3G. Q3G also exhibited the anti-inflammatory effects on the LPS-treated cells with a reduction in the activation of NLRP3 [nucleotide-binding and oligomerization domain (NOD)-like receptor protein 3] inflammasome, leading to pyroptosis. Also, Q3G showed the anti-apoptotic effect in the cells might be mediated via inhibition of mitochondrial apoptosis pathway. To further explore in vivo pulmonary-protective effect of Q3G, C57BL/6 mice were intranasally exposed to a combination of LPS and elastase (LPS/E) to perform the pulmonary injury model. The results revealed that Q3G ameliorated pulmonary function parameters and lung edema in the LPS/E-induced mice. Q3G also suppressed the LPS/E-stimulated inflammation, pyroptosis and apoptosis in the lungs. Taken together, this study suggested the lung-protective potential of Q3G via downregulation of inflammation, pyroptotic and apoptotic cell death, contributing to its chemopreventive activity of pulmonary injury.

Background: Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study., Methods: A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan-Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease., Results: At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55-0.97] for prediabetic and 1.48 (95% CI 1.11-1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB., Conclusions: Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Lead (Pb) is a toxic metal that has been extensively used in various industrial processes, and it persists in the environment, posing a continuous risk of exposure to humans. This study investigated blood lead levels in participants aged 20 years and older, who resided in Dalinpu for more than two years between 2016 to 2018, at Kaohsiung Municipal Siaogang Hospital. Graphite furnace atomic absorption spectrometry was used to analyze the blood samples for lead levels, and the LDCT (Low-Dose computed tomography) scans were interpreted by experienced radiologists. The blood lead levels were divided into quartiles, with Q1 representing levels of ≤1.10 μg/dL, Q2 representing levels of >1.11 and ≤1.60 μg/dL, Q3 representing levels of >1.61 and ≤2.30 μg/dL, and Q4 representing levels of >2.31 μg/dL. Individuals with lung fibrotic changes had significantly higher (mean ± SD) blood lead levels (1.88±1.27vs. 1.72±1.53 μg/dl, p< 0.001) than those with non-lung fibrotic changes. In multivariate analysis, we found that the highest quartile (Q4: >2.31 μg/dL) lead levels (OR: 1.36, 95% CI: 1.01-1.82; p= 0.043) and the higher quartile (Q3: >1.61 and ≤2.30 μg/dL) (OR: 1.33, 95% CI: 1.01-1.75; p= 0.041) was significantly associated with lung fibrotic changes compared with the lowest quartile (Q1: ≤1.10 μg/dL) (Cox and Snell R 2 , 6.1 %; Nagelkerke R 2 , 8.5 %). The dose-response trend was significant (P trend = 0.030). Blood lead exposure was significantly associated lung fibrotic change. To prevent lung toxicity, it is recommended to maintain blood lead levels lower than the current reference value., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration., Methods: A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population., Results: A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11-3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33-0.92)., Conclusions: Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target proteinase 3 (PR3) or myeloperoxidase (MPO) found within neutrophils and monocytes. Granulomas are exclusively found in GPA and form around multinucleated giant cells (MGCs), at sites of microabscesses, containing apoptotic and necrotic neutrophils. Since patients with GPA have augmented neutrophil PR3 expression, and PR3-expressing apoptotic cells frustrate macrophage phagocytosis and cellular clearance, we investigated the role of PR3 in stimulating giant cell and granuloma formation., Methods: We stimulated purified monocytes and whole peripheral blood mononuclear cells (PBMCs) from patients with GPA, patients with MPA or healthy controls with PR3 or MPO and visualised MGC and granuloma-like structure formation using light, confocal and electron microscopy, as well as measuring the cell cytokine production. We investigated the expression of PR3 binding partners on monocytes and tested the impact of their inhibition. Finally, we injected zebrafish with PR3 and characterised granuloma formation in a novel animal model., Results: In vitro, PR3 promoted monocyte-derived MGC formation using cells from patients with GPA but not from patients with MPA, and this was dependent on soluble interleukin 6 (IL-6), as well as monocyte MAC-1 and protease-activated receptor-2, found to be overexpressed in the cells of patients with GPA. PBMCs stimulated by PR3 formed granuloma-like structures with central MGC surrounded by T cells. This effect of PR3 was confirmed in vivo using zebrafish and was inhibited by niclosamide, a IL-6-STAT3 pathway inhibitor., Conclusions: These data provide a mechanistic basis for granuloma formation in GPA and a rationale for novel therapeutic approaches., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The objective of this study was to develop a rapid prediction method for carbapenem-resistant Klebsiella pneumoniae (CRKP) and colistin-resistant K. pneumoniae (ColRKP) based on routine MALDI-TOF mass spectrometry (MS) results in order to formulate a suitable and rapid treatment strategy. A total of 830 CRKP and 1462 carbapenem-susceptible K. pneumoniae (CSKP) isolates were collected; 54 ColRKP isolates and 1592 colistin-intermediate K. pneumoniae (ColIKP) isolates were also included. Routine MALDI-TOF MS, antimicrobial susceptibility testing, NG-Test CARBA 5, and resistance gene detection were followed by machine learning (ML). Using the ML model, the accuracy and area under the curve for differentiating CRKP and CSKP were 0.8869 and 0.9551, respectively, and those for ColRKP and ColIKP were 0.8361 and 0.8447, respectively. The most important MS features of CRKP and ColRKP were m/z 4520-4529 and m/z 4170-4179, respectively. Of the CRKP isolates, MS m/z 4520-4529 was a potential biomarker for distinguishing KPC from OXA, NDM, IMP, and VIM. Of the 34 patients who received preliminary CRKP ML prediction results (by texting), 24 (70.6%) were confirmed to have CRKP infection. The mortality rate was lower in patients who received antibiotic regimen adjustment based on the preliminary ML prediction (4/14, 28.6%). In conclusion, the proposed model can provide rapid results for differentiating CRKP and CSKP, as well as ColRKP and ColIKP. The combination of ML-based CRKP with preliminary reporting of results can help physicians alter the regimen approximately 24 h earlier, resulting in improved survival of patients with timely antibiotic intervention., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Few literatures discussed the relationship of glycemic control and body mass index (BMI) with the risk of pyogenic liver abscess. We conducted a population-based cohort study using participants of a community-based health screening program in Taiwan from 2005 to 2008 (n = 125,865). Information on fasting plasma glucose (FPG), BMI, and other potential risk factors of liver abscess were collected at baseline. Incidence of pyogenic liver abscess was ascertained using inpatient records from the National Health Insurance database. During a median 8.6 years of followed up, 192 incident cases of pyogenic liver abscess were reported. The incidence rate of pyogenic liver abscess was 70.2 and 14.7 per 100,000 in the diabetic and non-diabetic population respectively. In multivariable Cox regression analysis, the adjusted hazard ratio (HR) was 2.18 (95% confidence interval (CI) 1.22-3.90) in patients with diabetes with good glycemic control (FPG ≤ 130 mg/dl) and 3.34 (95% CI 2.37-4.72) in those with poor glycemic control (FPG > 130 mg/dl), when compared with non-diabetics. In the dose-response analysis, the risk of liver abscess increased monotonically with increasing FPG. After adjusting for diabetes and other comorbidities, overweight (25 ≤ BMI < 30) (adjusted HR: 1.43, 95% CI 1.05-1.95) and obese (BMI ≥ 30) (adjusted HR: 1.75, 95% CI 1.09-2.81) populations had a higher risk of liver abscess when compared to people with normal weight. Diabetes, especially poorly controlled disease, and high BMI were associated with higher risk of pyogenic liver abscess. Improving glycemic control and weight reduction may reduce the risk of developing pyogenic liver abscess., (© 2023. The Author(s).)

Background: Approximately 10-40% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI)., Methods: The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib/RT/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM)., Results: At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib/RT/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% ( p < 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib/RT/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM ( p < 0.001) in patients who received multiple therapeutic modalities., Conclusion: Multimodality therapy with sorafenib/RT/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials.

Background: Since entering the 21 st century, there has been an increasing interest in minimally invasive surgery for spinal diseases, which has led to the continued development of minimally invasive spine surgery (MISS), with major breakthroughs in technology and technical skills. However, in recent years, there is little relevant research using bibliometrics to analyze the field of MISS research. The purpose of this study is to sort out the publication situation and topic trends of articles in the field of MISS research from the perspective of bibliometrics., Methods: The articles and reviews related to MISS from 2000 to 2022 were retrieved and downloaded from the Web of Science Core Collection (WOSCC). Visualization and knowledge mapping were performed using three bibliometric tools, including online bibliometric platform, CiteSpace and VOSviewer software. Curve fitting and correlation analysis were performed using Microsoft Excel software. The global research publication output, contributions of countries, institutions, authors, and journals, average citations per item (ACI), Hirsch index ( H -index), research hot keywords, etc., in this field were analyzed., Results: A total of 2384 papers were retrieved, including 2135 original papers and 249 review papers. In the past 22 years, the number of annual publications of MISS research has shown a steady growth trend. China contributed the most papers, and the United States ranked second, but the United States had the highest total citations, and H -index value. The most prolific institutions were Soochow University, Capital Medical University and Wooridul Spine Hospital. In this field, Professors Lee SH, Ahn Y and Yang HL have made significant achievements. However, there is relatively little international collaboration between institutions or researchers. World Neurosurgery is the most published journal on MISS research. According to the keyword co-occurrence analysis, recent keywords mainly focus on researches on minimally invasive modalities, techniques and prognosis, while on the keyword analysis of the ongoing bursts, percutaneous transforaminal endoscopic discectomy, lumbar diskectomy, spinal stenosis, recompression, diskectomy, endoscopic spine surgery, laminectomy, transforaminal lumbar interbody fusion, etc., will likely continue to be a research hotspot in the near future., Conclusion: Looking at the temporal trend in the number of publications per year, the number of publications for the MISS study will increase in the near future. China has the highest number of publications, but the US has the highest quality publications. International cooperation needs to be further strengthened. Our findings can provide useful information for the academic community and identify possible research fronts and hotspots in the coming years., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracellular enzymatic processing and antigen presentation of an oligosaccharide-conjugate cancer vaccine prepared from the glycan of Globo-H (GH), a globo-series glycosphingolipid (GSL). This oligosaccharide-conjugate vaccine was shown to elicit antibodies against the glycan moieties of all three globo-series GSLs that are exclusively expressed on many types of cancer and their stem cells. To understand the specificity and origin of cross-reactivity of the antibodies elicited by the vaccine, we found that the vaccine is first processed by fucosidase 1 in the early endosome of dendritic cells to generate a common glycan antigen of the GSLs along with GH for MHC class II presentation. This work represents the first study of oligosaccharide processing and presentation and is expected to facilitate the design and development of glycoconjugate vaccines based on oligosaccharide antigens.

Objectives: To identify cage and end plate factors of cage subsidence (CS) in patients who underwent oblique lateral interbody fusion (OLIF) and their association with patient-reported outcomes., Methods: Sixty-one patients (43 women and 18 men), with a total of 69 segments (138 end plates) which underwent OLIF at a single academic institution between November 2018 and November 2020, were included. All the end plates were separated into CS and nonsubsidence groups. Cage-related parameters (cage height, cage width, cage insertion level, and cage position) and end plate-related parameters (position of end plate, Hounsfield unit value of the vertebra, end plate concave angle [ECA], end plate injury, and angular mismatch measured with cage/end plate angle [C/EA]) were compared and analyzed using logistic regression to predict CS. Receiver operating characteristic curve analysis was used to determine the cutoff points of the parameters., Results: Postoperative CS was identified in 50 of the 138 end plates (36.2%). The CS group had significantly lower mean Hounsfield unit values of the vertebra, higher rate of end plate injury, lower ECA, and higher C/EA than the nonsubsidence group. ECA and C/EA were identified as independent risk factors for developing CS. The optimal cutoff points for ECA and C/EA were 176.9° and 5.4°, respectively., Conclusions: An ECA greater than 176.9° and a cage/end plate angular mismatch greater than 5.4° were found to be independent risk factors of postoperative CS after the OLIF procedure. These findings aid in preoperative decision-making and intraoperative technical guidance., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) is the third most lethal cancer in the world, and its incidence is steadily rising. In this study, we investigated the induction of humoral immunity by a phytogalactolipid enriched fraction (CRA) derived from the medicinal plant Crassocephalum rabens (Benth.) S. Moore to combat CRC., Methods: Immunocompetent BALB/c mice were used to evaluate CRA's therapeutic effects in CRC. The phenotypes of B cell subsets in splenocytes and tumors from the CRA-treated mice were isolated and analyzed by flow cytometry. The titers, isotypes, specificity, antigen recognition, and cytotoxic activity of CRA-induced anti-tumor antibodies were determined. The mechanisms of CRA on B cell differentiation were determined by cell-based analyses, including co-cultural with T cells, cytokine analysis, gene expression by qPCR, and protein expression by western blotting., Results: CRA efficiently inhibited tumor growth in colorectal tumor-bearing allograft mice. CRA treatment attracted an abundance of B cells into the tumor consequently enhancing the anti-tumor antibodies in sera and inducing a class-switch. CRA-induced antisera (designated CRA antisera) specifically recognized surface antigens on the plasma membrane of cancer cells. CRA antisera induced cytotoxicity including antibody-dependent cell cytotoxicity, phagocytosis, and complement-dependent cytotoxicity. CRA interacted with IL-6 receptor to activate STAT3 and cMaf, resulting in T cell secretion of IL-21, which, in turn induced B cell differentiation through the IL-21R/STAT3/Blimp-1 pathway., Conclusions: CRA regulated T cell activity resulting in B cell activation and triggering of anti-tumor antibodies to impede CRC progression., (© 2023. The Author(s).)

Background: Cement-augmented pedicle screws (CPS) and hybrid construct (HC), consisting of pedicle screws and additional hooks, are common fixation methods for osteoporotic spine fracture. No study has compared surgical results of CPS and HC for treating osteoporotic spine fracture. The aim of the study was to compare surgical results using CPS or HC for osteoporotic fractures of the thoracic or lumbar spine., Methods: This retrospective cohort study included 84 patients who received surgical treatment with CPS (n = 43) or HC (n = 41) for osteoporotic spine fractures from January 2011 to December 2015, with a mean follow-up of 67 months. Sixty-five patients with neurological deficits received long posterior instrumentation, short posterior decompression, and posterolateral fusion. The 19 patients without neurologic deficits received long posterior instrumentation without posterior decompression and fusion. Radiographic, clinical, and neurologic outcomes were evaluated., Results: The HC group had significantly shorter operative times (231 vs 258 minutes), greater blood loss (497 vs 427 mL), better immediate postoperative kyphosis reduction (10.6° vs 9.1°), and greater final reduction loss (9.8° vs 7.1°) than the CPS group. In both groups, significant loss of the kyphotic angle was apparent during follow-up. Improved ambulation after surgery occurred in 51.2% and 58.5% of patients in the CPS and HC groups, respectively. Neurologic function after surgery improved 0.5 and 0.7 grades in the CPS and HC groups, respectively. Implants failed in 2.3% and 2.4% of patients in the CPS and HC groups, respectively. The incidence of cement leakage from screw augmentation was 38.9%., Conclusion: The CPS and HC techniques for treating osteoporotic fractures of the thoracic or lumbar spine did not differ statistically in terms of improved radiologic and clinical outcomes, final neurologic and ambulatory function, or implant failure rates, making them equally comparable alternatives., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Objective: To evaluate the efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer (CRC) patients with synchronous liver-only metastases non-responsive to bevacizumab-based chemotherapy (BBC)., Methods: Fifty-eight patients were enrolled in this study. Treatment response to BBC and DEBIRI were determined by the morphological criteria and Choi's criteria, respectively. Progression-free survival (PFS) and overall survival (OS) were recorded. The correlation between pre-DEBIRI CT parameters and treatment response to DEBIRI was analyzed., Results: CRC patients were divided into the BBC responsive group (R group) ( n = 16) and the non-responsive group ( n = 42), which was further divided into the NR group (23 patients who did not receive DEBIRI) and the NR+DEBIRI group (19 patients who received DEBIRI after failing BBC). Among the R, NR and NR+DEBIRI groups, the median PFS were 11, 12, and 4 months, respectively ( p < 0.01); median OS were 36, 23, and 12 months, respectively ( p = 0.01). In the NR+DEBIRI group, 33 metastatic lesions were treated with DEBIRI, of which 18 (54.5%) reached objective response. The receiver operating characteristic curve showed that the contrast enhancement ratio (CER) before DEBIRI could predict objective response (AUC = 0.737, p < 0.01)., Conclusion: In CRC patients, DEBIRI can achieve acceptable objective response for liver metastases non-responsive to BBC. However, this locoregional control does not prolong survival. The pre-DEBIRI CER can predict OR in these patients., Advances in Knowledge: DEBIRI can act as an acceptable locoregional management in CRC patients with liver metastases non-responsive to BBC, and the pre-DEBIRI CER is a potential indicator of locoregional control.

Background: Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers and hepatitis virus was believed to have the potential for altering the pathogenesis of arteriosclerosis. However, the influence of the hepatitis virus on coronary artery disease or cerebral vascular disease remains unclear. This study used the Taiwan National Health Insurance Research Database to clarify the virus-associated risk of coronary artery disease and cerebral vascular disease in patients with hepatocellular carcinoma (HCC)., Methods: A total of 188,039 HCC individuals, age 20 years or older, were enrolled from the Longitudinal Health Insurance Database between 2000 and 2017 for cohort analysis. A total of 109,348 with hepatitis B virus (HBV) infection, 37,506 with hepatitis C virus (HCV) infection, 34,110 without HBV or HCV, and 7075 with both HBV and HCV were recorded. Statistically, propensity score matched by sex, age, and index year at a ratio of 15:5:5:1 and a sensitivity test using multivariable Cox regression were used., Results: The risk of coronary artery disease in the HCV-related HCC group was 1.516-fold (95% CI: 1.328-2.034, p < 0.001) higher than in the HBV-related HCC group, followed by the HBV/HCV-related HCC group and the non-B/C HCC group; the cerebral vascular disease risk in the HCV-related HCC group was 1.467-fold higher than in the HBV-related HCC group (95% CI: 1.335 to 1.786, p < 0.001), followed by the HBV/HCV-related HCC group and the non-B/C HCC group., Conclusion: Hepatitis C virus infection was found to have a higher risk of developing coronary artery disease or cerebral vascular disease in patients with hepatocellular carcinoma. For patients with hepatocellular carcinoma, our findings warrant the importance in preventing artherosclerotic disease in the setting of hepatitis C virus infection.

An important consideration in medical plastic surgery is the evaluation of the patient's facial symmetry. However, because facial attractiveness is a slightly individualized cognitive experience, it is difficult to determine face attractiveness manually. This study aimed to train a model for assessing facial attractiveness using transfer learning while also using the fine-grained image model to separate similar images by first learning features. In this case, the system can make assessments based on the input of facial photos. Thus, doctors can quickly and objectively treat patients' scoring and save time for scoring. The transfer learning was combined with CNN, Xception, and attention mechanism models for training, using the SCUT-FBP5500 dataset for pre-training and freezing the weights as the transfer learning model. Then, we trained the Chang Gung Memorial Hospital Taiwan dataset to train the model based on transfer learning. The evaluation uses the mean absolute error percentage (MAPE) value. The root mean square error (RMSE) value is used as the basis for experimental adjustment and the quantitative standard for the model's predictive. The best model can obtain 0.50 in RMSE and 18.5% average error in MAPE. A web page was developed to infer the deep learning model to visualize the predictive model.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yang 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.)

Disorders of the immune system, including immunodeficiency, immuno-malignancy, and (auto)inflammatory, autoimmune, and allergic diseases, have a great impact on a host's health. Cellular communication mediated through cell surface receptors, among different cell types and between cell and microenvironment, plays a critical role in immune responses. Selective members of the adhesion G protein-coupled receptor (aGPCR) family are expressed differentially in diverse immune cell types and have been implicated recently in unique immune dysfunctions and disorders in part due to their dual cell adhesion and signaling roles. Here, we discuss the molecular and functional characteristics of distinctive immune aGPCRs and their physiopathological roles in the immune system.

Metal artifacts present a major challenge to computed tomography (CT) because they reduce the image quality in medical diagnosis and treatment. Several metal artifact reduction (MAR) methods have been proposed to address this issue in previous studies. This study aimed to synthesize a virtual monochromatic image for MAR in CT images using projection-based material decomposition (MD) algorithms. We developed a spectral micro-CT prototype system equipped with a photon-counting detector (PCD) and PCD-CT imaging simulator to assess the performances of different MAR methods. Two projection-based MD algorithms were implemented and evaluated for their MAR performances in CT images and compared with conventional sinogram inpainting MAR methods. Different parts of digital 4D-extended cardiac torso (XCAT) phantoms with metal implants were designed to simulate various real scenarios. A homemade metal artifact evaluation (MAE) phantom was used to evaluate the MAR performance in experiments. The simulated results of the XCAT phantom indicated that the projection-based virtual monochromatic CT (VMCT) images provided better image quality than the conventional MAR images without blurring the normal tissues at the position of the metal artifacts. Various quantitative indicators support this conclusion. Additionally, the experimental results of the MAE phantom reveal that projection-based VMCT images can avoid image distortion caused by metal artifacts, unlike conventional MAR methods. In regards to the projection-based VMCT images, the simulated and experimental results demonstrated that using the linear maximum likelihood estimators with an error correction look-up table algorithm yielded better MAR performance compared to that obtained using a polynomial algorithm. Furthermore, projection-based VMCT images can not only reduce metal artifacts effectively but also simultaneously prevents object blurring at the metal artifact position and image distortion of the metal implants. Hence, the CT image quality can be further improved to increase the abilities for both preoperative and postoperative assessment of metal implants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chang 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.)

Ethanol consumption influences cardiovascular functions. In humans, acute consumption of ethanol causes dose-dependent tachycardia. Our previous study showed that ethanol-induced tachycardia might involve decreased nitric oxide (NO) signaling in the brain's medulla. NMDA receptors, another important target of ethanol, are one of the upstream signals of nitric oxide. Reports showed the modulation of NMDA receptor function by estrogen or estrogen receptors. The present study aims to examine the hypothesis that depletion of estrogen by ovariectomy (OVX) might modulate ethanol-induced tachycardia by regulating NMDA receptor function and NO signaling in the cardiovascular regulatory nucleus of the brain. Ethanol (3.2 g/kg, 40% v / v , 10 mL/kg) or saline (10 mL/kg) was administered by oral gavage in sham or OVX female Sprague-Dawley (SD) rats. The blood pressure (BP) and heart rate (HR) were measured using the tail-cuff method. The levels of phosphoserine 896 of the GluN1 subunit (pGluN1-serine 896) and NMDA GluN1 subunits (GluN1) were determined by immunohistochemistry. The expressions of nitric oxide synthase (NOS) and estrogen receptors in the tissue were measured by Western blotting. Nitric oxide contents were measured as total nitrate-nitrite by colorimetric assay kit. In a 2-h observation, there was no significant change in BP between the saline and ethanol groups. However, compared with saline, ethanol caused an increase in HR (tachycardia) in sham control or OVX rats. Interestingly, ethanol produced more significant tachycardia in the OVX group than in the sham control group. Nitric oxide levels were lower in the area of the rostral ventrolateral medulla (RVLM) 60 min following ethanol administration in OVX compared with sham control, without significant changes in the expression of NOS and estrogen receptors (ERα and ERβ). In addition, a decrease in the immunoreactivity of pGluN1-serine 896, without significant changes in GluN1, was found in neurons of RVLM 40 min following ethanol administration in OVX compared with sham control. Our results suggest that depletion of estradiol (E2) by OVX might exacerbate the tachycardia following ethanol administration, the underlying mechanism of which might be associated with decreased NMDA receptor function and NO level in the RVLM.

Background: No consensus exists regarding the timing or technique of rhinoplasty for correction of the unilateral cleft lip nose deformity, with few studies examining the long-term effects of a single technique. This study appraised the long-term outcomes of primary rhinoplasty using the Tajima technique for overcorrection in a cohort of patients with unilateral cleft lip nose deformity after attaining skeletal maturity., Methods: Consecutive nonsyndromic patients with unilateral cleft lip nose deformity ( n = 103) who underwent primary rhinoplasty with overcorrection by a single surgeon between 2000 and 2005 were reviewed. Patients with unilateral cleft lip and nasal deformity who underwent primary rhinoplasty (but with no overcorrection) ( n = 30) and noncleft individuals ( n = 27) were recruited for comparison. Outcomes were assessed through FACE-Q scales evaluating satisfaction with appearance of nose and nostrils (two scales) and computer-based objective photogrammetric analysis of nasal symmetry (nostril height, nostril width, nostril area, alar height, and alar width parameters)., Results: Significant differences (all P < 0.001) were observed between the Tajima and non-Tajima groups for all but one photogrammetric nasal parameter (nostril area), with the Tajima group demonstrating closer mean values to the noncleft group. The Tajima and noncleft groups demonstrated no significant difference (all P > 0.05) for scores of FACE-Q nose and nostrils scales., Conclusion: This study indicated that the patients who underwent primary rhinoplasty with overcorrection had improved results with no necessity for intermediate rhinoplasty, emphasizing that the procedure is an effective approach to correct the unilateral cleft nose deformity., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: The dynamic Dynesys Stabilization System preserves lumbar mobility at instrumented levels. This study investigated the effect of screw length on screw loosening (SL) after dynamic Dynesys fixation and screw displacement during lumbar motion, using clinical investigation and finite-element (FE) analysis., Methods: Clinical data of 50 patients with degenerative spondylolisthesis treated with decompression and Dynesys fixation in 2011 were analyzed retrospectively. Horizontal sliding displacement and vertical displacement of screw tips at L4 were analyzed postoperatively using displacement-controlled FE analysis at the L4-L5 level with screw lengths 45 (long screw), 36 (median screw), and 27 (short screw), and 6.4 mm in diameter, under flexion, extension, lateral bending, and rotation., Results: In 13 patients (13/50, 26%), 40 screws (40/266, 15%) were loose at mean follow-up of 101.3 ± 4.4 months. Radiographic SL at 35, 40, 45, and 50 mm were 7.7%, 10.7%, 12.1%, and 37.5%, respectively, regardless of the fixation level ( p = 0.009). FE analysis revealed that the long screw model with corresponding longer lever arm had maximal horizontal sliding displacement under all directions and maximal vertical displacement, except for lateral bending., Conclusion: Shorter screws in Dynesys fixation may help avoid dynamic SL. Clinically, 50 mm screws showed the greatest SL and median screw screws demonstrated the least displacement biomechanically., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Study Design: Retrospective case-control study., Objectives: This study aims to present the clinical and radiographical outcomes of the titanium-polyetheretherketone (Ti/PEEK) composite cage compared to those of the standard PEEK cage in patients receiving minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)., Methods: Patients receiving 1 level MI-TLIF between October 2015 and October 2017 were included with a minimum of 2-year follow-up. The patients were segregated into 2 groups; Ti/PEEK group and PEEK group. Each patient was propensity-matched using preoperative age, sex, and body mass index. Early fusion rate was evaluated by computed tomography at postoperative 6 months. Clinical outcomes were assessed using the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores., Results: After matching, there were 27 patients included in each group. The demographics, diagnosis, and surgical details were not significantly different between the 2 groups. The 6-month rate was 88.9% in Ti/PEEK group. The fusion rate and cage subsidence rate had no difference between the 2 groups. The complication rate in the Ti/PEEK group was comparable to that in the PEEK group. There was no difference in VAS and ODI scores during a 2-year follow-up period., Conclusions: The use of Ti/PEEK composite cage was as safe and effective as the use of PEEK cage in MI-TLIF. The 6-month fusion rate was 88.9%. Our finding revealed comparable clinical results for surgeons using Ti/PEEK composite cages in MI-TLIF compared to those using the PEEK cage.

Objective: Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic-related migration disorder. It has been attributed to loss-of-function of the ADGRG1 gene, which encodes an adhesion G protein-coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro)., Methods: We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole-exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting., Results: The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole-exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High-amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre-school age. Partial callosotomy provided short-term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3., Significance: Sleep EEG findings of high-amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: The distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation., Methods: In this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs)., Results: Knockdown of YULINK during the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown of YULINK in HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased in YULINK knockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised in YULINK knockdown HUVECs, demonstrating to the involvement of YULINK., Conclusion: This study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs., (© 2023. The Author(s).)

Osteoporosis is a progressive metabolic bone disorder characterised by a decline in bone mineral density (BMD). Some previous studies have reported a controversial relationship between uric acid and osteoporosis. This cross-sectional study aimed to assess the association between serum uric acid levels and BMD in older adults from Taiwan. Data from participants aged ≥ 60 years were collected from 2008 to 2018. Furthermore, the participants were classified based on uric acid level quartiles. Regression models were used to assess the association between uric acid levels and bone health, including BMD values and risk of at least osteopenia. Crude and adjusted models of potential confounders, including age, sex and body mass index (BMI), were used. Compared with the first quartile of uric acid levels, the odds ratios for osteoporosis decreased in the higher uric acid level groups after adjustment for age, sex and BMI. The boxplot analysis showed that BMD values were higher in the groups with higher uric acid levels; moreover, the results of the multivariable linear regression model showed a consistent pattern. Notably, uric acid levels were positively correlated with BMD values. Higher uric acid levels in the elderly population might decrease the risk of at least osteopenia. As opposed to the anti-hyperuricemic policy for younger adults with a relatively lower risk of osteoporosis, BMD evaluation and urate-lowering therapy, goal adjustments should be considered for older adults with lower uric acid levels.

We report on the design of an attached guard ring (AGR) and a floating guard ring (FGR) in a planar separate absorption, grading, charge, and multiplication In 0.53 Ga 0.47 As/InP avalanche photodiode to prevent premature edge breakdowns. The depths of the two Zn diffusions were utilized to manipulate the guard ring structures. Results from TCAD simulation indicate that the optimal AGR diffusion depth is right at the turning point where the breakdown current shifts from the edge of active region to the AGR region. The devices with optimal AGR depth contain significantly higher breakdown voltages than those of devices either with shallower-or without any- AGR. For the FGR design, a series of devices with different spacings between AGR and FGR and different FGR opening widths for diffusion were fabricated and characterized. We show that when the spacing is longer than the critical value, the breakdown voltage can increase ~1.5 V higher than those of the APD devices without FGR. In addition, the wider the FGR opening width, the higher the breakdown voltage. TCAD simulations were also performed to study the effect of FGR, but showed less pronounced improvements, which could be due the discrepancy between the calculated and experimental diffusion profile.

Objectives: Laparoscopic hepatectomy (LH) is still technically challenging for patients with previous nonhepatectomy abdominal surgery (AS). Therefore, this study aimed to assess the difficulty of performing LH for patients with hepatocellular carcinoma (HCC) and a history of nonhepatectomy AS during the initial developing period of LH., Materials and Methods: The retrospective study enrolled patients who were newly diagnosed with HCC receiving LH from January 2013 to June 2021. Demographic characteristics, perioperative variables, and surgical complications were prospectively collected., Results: One hundred patients were reviewed consecutively, comprising 23 in the AS group and 77 in the non-AS group. No significant differences were observed in median IWATE score (5 vs. 5, P = 0.194), operative time (219 vs. 200 min, P = 0.609), blood loss (100.0 vs. 200.0 mL, P = 0.734), transfusion rate (4.3% vs. 10.4%, P = 0.374), duration of parenchyma transection (90.0 vs. 72.4 min, P = 0.673), and mean nonparenchymal transection time (191.0 vs. 125.0 min, P = 0.228), without increasing the conversion rate (0.0% vs. 3.9%, P = 0.336), postoperative complications (30.3% vs. 33.8%, P = 0.488), and postoperative hospital stay (6 vs. 7 days, P = 0.060) in AS group and non-AS groups., Conclusion: History of previous nonhepatectomy AS can lead to longer nonparenchymal transection time instead of conversion and did not increase the difficulty. Prolonged nonparenchymal transection time did not increase the surgical complications, prolong the postoperative hospital stay, and compromise the survival outcomes., Competing Interests: Dr. Ming-Che Lee, an editorial board member at Tzu Chi Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2023 Tzu Chi Medical Journal.)

Chronic kidney disease (CKD) is a systemic inflammatory syndrome that includes tubulointerstitial inflammation. Lipopolysaccharide (LPS), the outer membrane of Gram-negative bacteria, can increase reactive oxygen species production (ROS) that triggers cell inflammation. Isovitexin (IV) is a flavone that has the potential for anticancer, antioxidant, and anti-inflammatory. This study aimed to hypothesize that IV inhibited LPS-induced renal injury in vitro and in vivo. In vitro study, IV prevented LPS-induced ROS production and increased cell viability on SV40-MES-13 cells. Additionally, IV ameliorated mitochondrial membrane potential, downregulated inflammation and pyroptosis factors on LPS treatment. We found that LPS treatment reduced the expression of autophagy, however, this effect was reversed by IV. In vivo study, the renal injury model in C57BL/6 mice cotreatment with IV was examined. In addition, IV decreased LPS-induced glomerular atrophy and reduced inflammation-related cytokines releases. Further showed that IV could significantly reduce LPS-induced inflammation and pyroptosis factors in mice. Under the immunostaining, increased fluorescence of LC3 autophagy-related protein was recovered by IV. In summary, IV ameliorated renal injury, inflammation and increased protected autophagy by anti-ROS production, anti-inflammation, and anti-pyroptosis. In the future, the safety of isovitexin as a novel perspective for CKD patients should be evaluated in further clinical studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jing-Hsien Chen reports financial support was provided by the Ministry of Science and Technology, Taiwan (MOST110-2320-B040-015)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Postvertebroplasty infection (PVI) is a catastrophic complication after vertebroplasty (VP). Although the urinary tract has been considered as a source of infectious pathogens, whether asymptomatic bacteriuria (ASB) is a risk factors for PVI remains unknown., Methods: This retrospective study included 716 patients (207 males; 509 females) treated with VP for osteoporotic vertebral fractures in a single medical center between May 2015 and December 2019. Clinical symptoms, urinalysis results, and culture data were collected preoperatively to identify patients with ASB. The primary outcome was PVI at the index level during follow-up. Demographic data and laboratory test results were compared between the PVI and non-PVI groups., Results: The mean age of the cohort was 78.6 ± 9.6 (range, 63-106). The prevalence of ASB was 14.1%, with female predominance (63.4%). The overall PVI rate was 1.26% (9/716). The PVI group had more patients with ASB (4/9, 44.4%) than did the non-PVI group (97/707, 13.7%) (p = 0.027). The rate of ASB treatment was similar between the PVI and non-PVI groups (25% vs. 23.7%, respectively). No case of PVI was caused by the urine culture pathogen. Multivariate analysis identified the following risk factors for PVI: ASB (odds ratio [OR], 5.61; 95% CI, 1.14-27.66; p = 0.034), smoking (OR, 16.26; 95% CI, 2.58-102.65; p = 0.003), and malignancy (OR 7.27; 95% CI, 1.31-40.31; p = 0.023)., Conclusion: ASB was not uncommon among patients admitted for VP and should be considered a marker of relatively poor host immunity. Preoperative ASB, a history of malignancy, and smoking were identified as significant risk factors for PVI., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with characteristics of high metastasis and poor prognosis. There are some particularly different features of UTUC between the Asian and Western countries. Double-strand break repair protein MRE11 is a component of the MRN complex that is involved in the DNA repair pathway. Emerging studies have focused on the role of MRE11 in human malignancies with conflicting results. We aimed to establish the relationship between MRE11 expression and the oncological outcome of UTUC. This study retrospectively reviewed 150 patients who underwent radical nephroureterectomy with pathologically confirmed UTUC. Pathologic slides were reviewed, and clinical parameters were collected. An immunohistochemical study was performed, and the cytoplasmic and nuclear-staining results of UTUC were recorded. The expression of MRE11 was analyzed to identify correlations with various clinicopathological parameters, metastasis-free survival, and cancer-specific survival (CSS). MRE11 expression was significantly correlated with patients with a high pathologic stage ( P =0.001), perineural invasion ( P =0.015), and tumor necrosis ( P =0.034). Upon univariate analysis, a high MRE11 expression was associated with poor metastasis-free survival ( P =0.014, 95% CI 1.18, 4.38) and poor CSS ( P =0.001, 95% CI 2.45, 27.75). Upon multivariable analysis, a high MRE11 expression was associated with poor CSS ( P =0.019, 95% CI 1.28, 15.65). In summary, MRE11 expression could serve as a potential predictor of prognosis in patients with UTUC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Soothing dolls are becoming increasingly popular in a society with a lot of physical and mental stress. Many products are also combined with soothing dolls to stimulate consumers' desire for impulse buying. However, there is no research on the relationship between consumers' purchasing behavior, consumers' preference for soothing dolls, and visual preference. The purpose of this study was to examine the possible factors that affect the emotional and visual preferences of soothing dolls. Two local stores' sales lists were used to extract three different types of dolls. The 2D and 3D versions of these three dolls were used. Subjective emotional preferences were examined by the self-assessment manikin (SAM) scale, with 5-point Likert scales for valence and arousal factors. An eye tracker was used to examine visual preferences, both before and after positive/negative emotion stimulation by the International Affective Picture System (IAPS). There were 37 subjects involved, with an age range of 20-28 years. The experimental results show that the average valence/arousal scores for 2D/3D dolls were (3.80, 3.74) and (2.65, 2.68), respectively. There was no statistical difference, but both 2D and 3D pictures had high valence scores. Eye tracker analysis revealed no gaze difference in visual preference between 2D and 3D dolls. After negative emotional picture stimulation, the observation time of the left-side doll decreased from 2.307 (std 0.905) to 1.947 (std 1.038) seconds, p < 0.001; and that of the right-side picture increased from 1.898 (std 0.907) to 2.252 (std 1.046) seconds, p < 0.001. The average observation time ratio of the eye on the 3D doll was 40.6%, higher than that on the 2D doll (34.3%, p = 0.02). Soothing dolls may be beneficial for emotion relaxation. Soothing dolls always have high valence features according to the SAM evaluation's measurement. Moreover, this study proposes a novel research model using an eye-tracker and the SAM for the SOR framework.

Retrospective cohort study. To validate computed tomography (CT) radiodensity in Hounsfield units (HU) as a prognostic marker for pedicle screw loosening or cage subsidence in minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). The retrospective study involved 198 patients treated with MI-TLIF. Screw loosening (SL), cage subsidence (CS), and fusion status were assessed by plain radiographs. The risk factors of SL and CS were identified using logistic regression. A total of 258 levels and 930 screws were analyzed. During a 2-year follow-up, 16.2% and 24.7% of patients had CS and SL respectively. The cut-off value of L1 HU for predicting SL or CS was 117. The L1 HU < 117 and BMI ≥ 25 were two independent risk factors. The risk of SL or CS was 4.1 fold in patients L1 HU < 117 and 2.6 fold in patients with BMI ≥ 25. For patients concurrently having BMI ≥ 25 and pre-op L1 HU < 117, the risk was 4.3 fold. Fusion rate and clinical outcome were comparable in patients with SL or CS. L1 HU < 117 and BMI > 25 were two independent risk factors that can be screened preoperatively for preventing SL or CS and lead to better management of patients undergoing MI-TLIF., (© 2023. The Author(s).)

We demonstrate a method for separating and resolving the dynamics of multiple emitters without the use of conventional filters. By directing the photon emission through a fixed path-length imbalanced Mach-Zehnder interferometer, we interferometrically cancel (or enhance) certain spectral signatures corresponding to one emissive species. Our approach, Spectrally selective Time-resolved Emission through Fourier-filtering (STEF), leverages the detection and subtraction of both outputs of a tuned Mach-Zehnder interferometer, which can be combined with time-correlated single photon counting (TCSPC) or confocal imaging to demix multiple emitter signatures. We develop a procedure to calibrate out imperfections in Mach-Zehnder interferometry schemes. Additionally, we demonstrate the range and utility of STEF by performing the following procedures with one measurement: (1) filtering out laser scatter from a sample, (2) separating and measuring a fluorescence lifetime from a binary chromophore mixture with overlapped emission spectra, (3) confocally imaging and separately resolving the standard fluorescent stains in bovine pulmonary endothelial cells and nearly overlapping fluorescent stains on RAW 264.7 cells. This form of spectral balancing can allow for robust and tunable signal sorting.

Oxidative stress is vital for pathophysiology of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Monoamine oxidase (MAO) is an important source of oxidative stress in the vascular system and liver. However, the effect of MAO inhibition on atherosclerosis and NAFLD has not been explored. In the present study, MAO A and B expressions were increased in atherosclerotic plaques in human and apolipoprotein E (ApoE)-deficient mice. Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. MAO B inhibition had no therapeutic effect on restenosis in the femoral artery wire-induced injury model in C57BL/6 mice. In the NAFLD mouse model, MAO B inhibition reduced lipid droplet deposition in the liver and hepatic total cholesterol and triglyceride levels in C57BL/6 mice fed high-fat diets for 10 weeks. Key enzymes for triglyceride and cholesterol biosynthesis (fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase, HMGCR) and inflammatory markers were inhibited, and cholesterol clearance was up-regulated (increased LDL receptor expression and reduced proprotein convertase subtilisin/kexin type 9, PCSK9, expression) by MAO B inhibition in the liver. These results were also demonstrated in the HepG2 liver cell model. Our data suggest that MAO B inhibition is a potential and novel treatment for atherosclerosis and NAFLD., (© 2023 The Author(s).)

Hyperuricemic nephropathy (HN) is caused by urate crystals that get deposited in the kidney and contribute to renal fibrosis. Uric acid (UA) has been proven to directly cause renal mesangial cell oxidative stress and fibrosis in the pathogenesis of HN. Some antioxidants can be used as chemopreventive agents of HN. Hibiscus sabdariffa leaf extracts (HLE), rich in polyphenol, have been shown to possess hypoglycemic, antioxidant, hypolipidemic, antiatherosclerotic, and anticancer effects. The aim of the study is to examine the inhibitory effect of HLE and its main component ellagic acid (EA) on renal fibrosis. In vitro , mouse renal glomerular mesangial SV40MES13 cells pretreated with UA were demonstrated to trigger obvious morphological changes and viability loss, as well as affect matrix metalloproteinases (MMPs) activities. Noncytotoxic doses of HLE and EA abolished the UA-induced cell injury and MMP-2/9 secretion. In addition, HLE and EA exhibited antioxidant and anti-inflammatory effects on the UA-treated cells with a reduction in transforming growth factor-beta (TGF-β) production. Next, the UA-activated pro-fibrotic factors, extracellular matrix (ECM) deposition, and epithelial-mesenchymal-transition (EMT) were inhibited by HLE or EA. Mechanistic assays indicated that antifibrotic effects of HLE might be mediated via TGF-β/Smad signaling, as confirmed by the transfection of Smad7 siRNA. In vivo , HLE and EA supplementations significantly alleviated HN development, which may result from inhibiting adenine-induced TGF-β production accompanying oxidative stress and inflammation, as well as fibrogenesis. Our data imply that EA-enriched HLE regulates the TGF-β/Smad signaling, which in turn led to reduced renal mesangial cell injury and fibrosis in HN and provided a new mechanism for its nephroprotective activity.

he first imported case of monkeypox in Taiwan was diagnosed in an Asian man with HIV-1 infection and asymptomatic COVID-19, returning from Germany. Atypical presentations included asynchronous skin lesions, anogenital lesions and prominent inguinal lymphadenopathy. Whole genomic sequence alignment indicate that the Taiwan strain clustered together with human monkeypox virus West African clade B.1, currently circulating in Europe. Prompt diagnosis and infection control measures are crucial to mitigate the spread of monkeypox., Competing Interests: Declaration of competing interests The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Superior facet joint violation (FJV) is a potential risk factor for adjacent segment disease following lumbar fusion surgery. We sought to conduct a systematic review and meta-analysis to compare screw-related superior FJV rates between the open and different minimally invasive (MI) techniques-fluoroscopy-based, 3D-image navigation, and navigation with robotic assistance-in adult lumbar fusion surgery., Methods: We searched original articles comparing the rates of screw-related FJV between the open and different MI techniques in adult lumbar fusion surgery for lumbar degenerative diseases in PubMed, EMBASE, and the Cochrane Library from inception to September 2021. We compared the numbers of top-level pedicle screws and associated superior FJVs in the main analyses and performed subgroup analysis based on different MI techniques to examine whether individual MI approaches differed in superior FJV rate. Risk ratio (RR) and 95% confidence interval (CI) were calculated in a random-effect meta-analysis., Results: Included in the meta-analysis were 16 articles with 2655 patients and 4638 top-level pedicle screws. The pooled analysis showed no significant difference in superior FJV rates between the MI and open groups (RR: 0.89, 95% CI: 0.62-1.28). The subgroup analysis demonstrated that the overall rates of superior FJV were 27.1% (411/1518) for fluoroscopy-based, 7.1% (43/603) for 3D-image navigation, and 3.2% (7/216) for navigation with robotic assistance. Compared with the open method, the overall RRs were 1.53 (95% CI: 1.19-1.96) for fluoroscopy-based, 0.41 (95% CI: 0.22-0.75) for 3D-image navigation, and 0.25 (95% CI: 0.08-0.72) for navigation with robotic assistance., Conclusion: Among the three common MI techniques, fluoroscopy-based can be associated with a higher risk of superior FJV, while both 3D-image navigation and navigation with robotic assistance may be associated with lower risks as compared with the open method. Considering the limitations of the study, more trials are needed to prove these clinical findings., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Backgrounds: Accumulating evidence has reported a high correlation between inflammatory markers and oncological outcomes in colorectal cancer. In the present study, we aimed to assess the prognostic values of five inflammatory markers in stage II colon cancer patients with different tumour locations., Methods: The consecutive stage II colon adenocarcinoma patients undergoing curative resection were analysed retrospectively. ROC curves and the area under the curve (AUCs) via bootstrap method were used to analyse the prognostic impact of various inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and prognostic nutrition index (PNI)., Results: A total of 768 patients were enrolled for analysis. In univariate analysis, right-sided colon cancer (RCC) patients have significantly higher mean levels of all inflammatory markers than left-sided colon cancer (LCC) patients. In multivariate analyses, high NLR in LCC (P = 0.025) and low PNI in both RCC (P = 0.049) and LCC (P = 0.027) were significantly associated with a worse OS while none of the inflammatory markers was found to have a significant impact on DFS or CSS., Conclusions: The profiles and prognostic impact of inflammatory markers are significantly different between stage II RCC and LCC patients. Researchers should take sidedness into consideration when addressing survival analysis of inflammatory markers., (© 2022 Royal Australasian College of Surgeons.)

Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low-toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photothermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE-mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of ∼72.0% and ∼79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti-metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment., 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 Elsevier Inc. All rights reserved.)

Evolutionary dynamics is well captured by the replicator equations when the population is infinite and well-mixed. However, the extinction dynamics is modified with finite and structured populations. Experiments on the non-transitive ecosystem containing three populations of bacteria found that the ecological stability sensitively depends on the spatial structure of the populations. Based on the Reference-Gamble-Birth algorithm, we use agent-based Monte Carlo simulations to investigate the extinction dynamics in the rock-paper-scissors ecosystem with finite and structured populations. On the fully-connected network, the extinction time in stable and unstable regimes falls into two universal functions when plotted with the rescaled variables. On the two dimensional grid, the spatial structure changes the transition boundary between stable and unstable regimes but doesn't change its extinction trend. The finding of universal scaling in extinction dynamics is unexpected, and may provide a powerful method to classify different evolutionary dynamics into universal classes., (© 2022. The Author(s).)