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

Chun-Yen Yu,1,* Po-Hsun Huang,1,* Leo Leung-Chit Tsang,1 Hsien-Wen Hsu,1 Wei-Xiong Lim,1 Ching-Chun Weng,1 Tung-Liang Huang,1 Chien-Chin Hsu,2 Chao-Long Chen,3 Hsin-You Ou,1 Yu-Fan Cheng1 1Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Yu-Fan Cheng; Hsin-You Ou, Tel/Fax +88677317123-3027, Email prof.chengyufan@gmail.com; ouhsinyou@gmail.comBackground: The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma.Methods: From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported.Results: Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level > 100.Conclusion: Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.Keywords: Yttrium-90 radioembolization, selective internal radiation therapy, hepatocellular carcinoma

The Dynesys dynamics stabilisation system was developed to maintain the mobility of motion segment of the lumbar spine in order to reduce the incidence of negative effects at the adjacent segments. However, the magnitude of cord pretension may change the stiffness of the Dynesys system and result in a diverse clinical outcome, and the effects of Dynesys cord pretension remain unclear. Displacement-controlled finite element analysis was used to evaluate the biomechanical behaviour of the lumbar spine after insertion of Dynesys with three different cord pretensions. For the implanted level, increasing the cord pretension from 100 to 300 N resulted in an increase in flexion stiffness from 19.0 to 64.5 Nm/deg, a marked increase in facet contact force (FCF) of 35% in extension and 32% in torsion, a 40% increase of the annulus stress in torsion, and an increase in the high-stress region of the pedicle screw in flexion and lateral bending. For the adjacent levels, varying the cord pretension from 100 to 300 N only had a minor influence on range of motion (ROM), FCF, and annulus stress, with changes of 6, 12, and 9%, respectively. This study found that alteration of cord pretension affects the ROM and FCF, and annulus stress within the construct but not the adjacent segment. In addition, use of a 300 N cord pretension causes a much higher stiffness at the implanted level when compared with the intact lumbar spine. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our goal was to describe the clinical spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by routine newborn screening and assess factors associated with elevations of octanoylcarnitine in newborns and characteristics associated with adverse clinical consequences of medium-chain acyl-CoA dehydrogenase deficiency. METHODS: The first 47 medium-chain acyl-CoA dehydrogenase deficiency cases detected by the New England Newborn Screening Program were classified according to initial and follow-up octanoylcarnitine values, octanoylcarnitine-decanoylcarnitine ratios, medium-chain acyl-CoA dehydrogenase genotype, follow-up biochemical parameters, and feeding by breast milk or formula. RESULTS: All 20 patients who were homozygous for 985A-->G had high initial octanoylcarnitine values (7.0-36.8 microM) and octanoylcarnitine-decanoylcarnitine ratios (7.0-14.5), whereas the 27 patients with 0 to 1 copy of 985A-->G exhibited a wide range of octanoylcarnitine values (0.5-28.6 microM) and octanoylcarnitine-decanoylcarnitine ratios (0.8-12.7). Initial newborn octanoylcarnitine values decreased by days 5 to 8, but the octanoylcarnitine-decanoylcarnitine ratio generally remained stable. Among 985A-->G homozygotes, breastfed newborns had higher initial octanoylcarnitine values than newborns who received formula. Adverse events occurred in 5 children, 4 985A-->G homozygotes and 1 compound heterozygote with a very high initial octanoylcarnitine: 2 survived severe neonatal hypoglycemia, 1 survived a severe hypoglycemic episode at 15 months of age, and 2 died as a result of medium-chain acyl-CoA dehydrogenase deficiency at ages 11 and 33 months. CONCLUSION: Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency has detected cases with a wide range of genotypes and biochemical abnormalities. Although most children do well, adverse outcomes have not been entirely avoided. Assessment of potential risk and determination of appropriate treatment remain a challenge. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021., Methods: We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination., Results: Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement., Conclusions: Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Background: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET)., Methods: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points., Results: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96)., Conclusion: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The anti-programmed death-ligand 1 (PD-L1) antibody is a standard therapy for advanced hepatocellular carcinoma (HCC). Tumor expression of PD-L1 can be induced upon stimulus. Because cyclin-dependent kinase 9 (CDK9) inhibition reduces the expression of inducible proteins, we explored the influence of CDK9 inhibition on PD-L1 expression in HCC cells. We found that PD-L1 expression was low in HCC cells; however, IFN-γ treatment increased this expression. CDK9 inhibitors AZD4573 and atuveciclib reduced the IFN-γ induced PD-L1 expression in a dose-dependent manner. CDK9 knockdown yielded similar results, but CDK9 overexpression reversed the influence of the CDK9 inhibitors. In the orthotopic mouse model, mice treated with a CDK9 inhibitor and an anti-PD-L1 antibody had significantly smaller tumors and exhibited longer survival than mice treated with either agent. In conclusion, CDK9 inhibition could reduce the expression of PD-L1 in HCC cells. Using both CDK9 inhibitors and anti-PD-L1 antibodies is more effective than using either agent alone., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.

Background: Although miscarriage and termination of pregnancy affect maternal mental illnesses on subsequent pregnancies, their effects on the positive mental health (e.g., eudaimonia) of both first-time and multi-time parents have received minimal attention, especially for fathers. This longitudinal study examines the effects of experiences of miscarriage and termination on parental well-being in subsequent pregnancies from prenatal to postpartum years, while simultaneously considering parity., Methods: Pregnant women and their partners were recruited during early prenatal visits in Taiwan from 2011 to 2022 and were followed up from mid-pregnancy to 1 year postpartum. Six waves of self-reported assessments were employed., Results: Of 1813 women, 11.3 % and 14.7 % had experiences of miscarriage and termination, respectively. Compared with the group without experiences of miscarriage or termination, experiences of miscarriage were associated with increased risks of paternal depression (adjusted odds ratio = 1.6, 95 % confidence interval [CI] = 1.13-2.27), higher levels of anxiety (adjusted β = 1.83, 95 % CI = 0.21-3.46), and lower eudaimonia scores (adjusted β = -1.09, 95 % CI = -1.99 to -0.19) from the prenatal to postpartum years, particularly among multiparous individuals. Additionally, experiences of termination were associated with increased risks of depression in their partner., Limitations: The experiences of miscarriage and TOP were self-reported and limited in acquiring more detailed information through questioning., Conclusions: These findings highlight the decreased well-being of men whose partners have undergone termination of pregnancy or experienced miscarriage, and stress the importance of interventions aimed at preventing adverse consequences among these individuals., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Pollen germination and tube growth are essential processes for successful fertilization. They are among the most temperature-vulnerable stages and subsequently affect seed production and determine population persistence and species distribution under climate change. Our study aims to investigate intra- and inter-specific variations in the temperature dependence of pollen germination and tube length growth and to explore how these variations differ for pollen from elevational gradients., Methods: We focused on three conifer species, Pinus contorta, Picea engelmannii, and Pinus ponderosa, with pollen collected from 350 to 2200m elevation in Washington State, USA. We conducted pollen viability tests at temperatures from 5 to 40°C in 5°C intervals. After testing for four days, we took images of these samples under a microscope to monitor pollen germination percentage (GP) and tube length (TL). We applied the Gamma function to describe the temperature dependence of GP and TL and estimated key parameters, including the optimal temperature for GP (Topt&#95;GP) and TL (Topt&#95;TL)., Key Results: Results showed that pollen from three species and different elevations within a species have different GP, TL, Topt&#95;GP, and Topt&#95;TL. The population with a higher Topt&#95;GP would also have a higher Topt&#95;TL, while Topt&#95;TL was generally higher than Topt&#95;GP, i.e., a positive but not one-to-one relationship. However, only Pinus contorta showed that populations from higher elevations have lower Topt&#95;GP and Topt&#95;TL and vice versa. The variability in GP increased at extreme temperatures, whereas the variability in TL was greatest near Topt&#95;TL., Conclusions: Our study demonstrates the temperature dependences of three conifers across a wide range of temperatures. Pollen germination and tube growth are highly sensitive to temperature conditions and vary among species and elevations, affecting their reproduction success during warming. Our findings can provide valuable insights to advance our understanding of how conifer pollen responds to rising temperatures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Dynamical compensation (DC) provides robustness to parameter fluctuations. As an example, DC enables control of the functional mass of endocrine or neuronal tissue essential for controlling blood glucose by insulin through a nonlinear feedback loop. Researchers have shown that DC is related to the structural unidentifiability and the P -invariance property. The P -invariance property is a sufficient and necessary condition for the DC property. DC has been seen in systems with at least three dimensions. In this article, we discuss DC and P -invariance from an adaptive control perspective. An adaptive controller automatically adjusts its parameters to optimise performance, maintain stability, and deal with uncertainties in a system., Results: We initiate our analysis by introducing a simplified two-dimensional dynamical model with DC, fostering experimentation and understanding of the system's behavior. We explore the system's behavior with time-varying input and disturbance signals, with a focus on illustrating the system's P -invariance properties in phase portraits and step-like response graphs., Conclusions: We show that DC can be seen as a case of ideal adaptive control since the system is invariant to the compensated parameter., (© 2024. The Author(s).)

Synthesis of coronavirus subgenomic mRNA (sgmRNA) is guided by the transcription regulatory sequence (TRS). sgmRNA derived from the body TRS (TRS-B) located at the 1a/1b protein gene is designated 1ab/sgmRNA. In the current study, we comprehensively identified the 1ab/sgmRNAs synthesized from TRS-Bs located at the 1a/1b protein genes of different coronavirus genera both in vitro and in vivo by RT‒PCR and sequencing. The results suggested that the degree of sequence homology between the leader TRS (TRS-L) and TRS-B may not be a decisive factor for 1ab/sgmRNA synthesis. This observation led us to revisit the coronavirus transcription mechanism and to propose that the disassociation of coronavirus polymerase from the viral genome may be a prerequisite for sgmRNA synthesis. Once the polymerase can disassociate at TRS-B, the sequence homology between TRS-L and TRS-B is important for sgmRNA synthesis. The study therefore extends our understanding of transcription mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

During coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA-protein pull-down assay, six DVG-encoded proteins were identified by LC-MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies., (© 2023. The Author(s).)

Background: Coronaviruses are pathogens of humans and animals that cause widespread and costly diseases. The development of effective strategies to combat the threat of coronaviruses is therefore a top priority. The conserved coronavirus octamer motif 5'GGAAGAGC3' exists in the 3' untranslated region of all identified coronaviruses. In the current study, we aimed to examine whether targeting the coronavirus octamer motif GGAAGAGC is a promising approach to develop coronavirus vaccine., Methods: Plaque assays were used to determine the titers of mouse hepatitis virus (MHV)-A59 octamer mutant (MHVoctm) and wild-type (wt) MHV-A59 (MHVwt). Western blotting was used for the determination of translation efficiency of MHVoctm and MHVwt. Plaque assays and RT-qPCR were employed to examine whether MHVoctm was more sensitive to interferon treatment than MHVwt. Weight loss, clinical signs, survival rate, viral RNA detection and histopathological examination were used to evaluate whether MHVoctm was a vaccine candidate against MHVwt infection in BALB/c mice., Results: In this study, we showed that (i) the MHVoctm with mutation of coronavirus octamer was able to grow to high titers but attenuated in mice, (ii) with the reduced multiplicity of infection (MOI), the difference in gene expression between MHVoctm and MHVwt became more evident in cultured cells, (iii) MHVoctm was more sensitive to interferon treatment than MHVwt and (iv) mice inoculated with MHVoctm were protected from MHVwt infection., Conclusions: Based on the results obtained from cultured cells, it was suggested that the synergistic effects of octamer mutation, multiplicity of infection and immune response may be a mechanism explaining the distinct phenotypes of octamer-mutated coronavirus in cell culture and mice. In addition, targeting the conserved coronavirus octamer motif is a strategy for development of coronavirus vaccine. Since the conserved octamer exists in all coronaviruses, this strategy of targeting the conserved octamer motif can also be applied to other human and animal coronaviruses for the development of coronavirus vaccines, especially the emergence of novel coronaviruses such as SARS-CoV-2, saving time and cost for vaccine development and disease control., (© 2023. The Author(s).)

How coronaviruses evolve by altering the structures of their full-length genome and defective viral genome (DVG) under dynamic selection pressures has not been studied. In this study, we aimed to experimentally identify the dynamic evolutionary patterns of the S protein sequence in the full-length genome and DVG under diverse selection pressures, including persistence, innate immunity and antiviral drugs. The evolutionary features of the S protein sequence in the full-length genome and in the DVG under diverse selection pressures are as follows: (i) the number of nucleotide (nt) mutations does not necessarily increase with the number of selection pressures; (ii) certain types of selection pressure(s) can lead to specific nt mutations; (iii) the mutated nt sequence can be reverted to the wild-type nt sequence under the certain type of selection pressure(s); (iv) the DVG can also undergo mutations and evolve independently of the full-length genome; and (v) DVG species are regulated during evolution under diverse selection pressures. The various evolutionary patterns of the S protein sequence in the full-length genome and DVG identified in this study may contribute to coronaviral fitness under diverse selection pressures.

Background: Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear., Methods: We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission., Results: We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions., Conclusions: This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis., (© 2023. National Science Council of the Republic of China (Taiwan).)

Background: In addition to the well-known coronavirus genomes and subgenomic mRNAs, the existence of other coronavirus RNA species, which are collectively referred to as noncanonical transcripts, has been suggested; however, their biological characteristics have not yet been experimentally validated in vitro and in vivo., Methods: To comprehensively determine the amounts, species and structures of noncanonical transcripts for bovine coronavirus in HRT-18 cells and mouse hepatitis virus A59, a mouse coronavirus, in mouse L cells and mice, nanopore direct RNA sequencing was employed. To experimentally validate the synthesis of noncanonical transcripts under regular infection, Northern blotting was performed. Both Northern blotting and nanopore direct RNA sequencing were also applied to examine the reproducibility of noncanonical transcripts. In addition, Northern blotting was also employed to determine the regulatory features of noncanonical transcripts under different infection conditions, including different cells, multiplicities of infection (MOIs) and coronavirus strains., Results: In the current study, we (i) experimentally determined that coronavirus noncanonical transcripts were abundantly synthesized, (ii) classified the noncanonical transcripts into seven populations based on their structures and potential synthesis mechanisms, (iii) showed that the species and amounts of the noncanonical transcripts were reproducible during regular infection but regulated in altered infection environments, (iv) revealed that coronaviruses may employ various mechanisms to synthesize noncanonical transcripts, and (v) found that the biological characteristics of coronavirus noncanonical transcripts were similar between in vitro and in vivo conditions., Conclusions: The biological characteristics of noncanonical coronavirus transcripts were experimentally validated for the first time. The identified features of noncanonical transcripts in terms of abundance, reproducibility and variety extend the current model for coronavirus gene expression. The capability of coronaviruses to regulate the species and amounts of noncanonical transcripts may contribute to the pathogenesis of coronaviruses during infection, posing potential challenges in disease control. Thus, the biology of noncanonical transcripts both in vitro and in vivo revealed here can provide a database for biological research, contributing to the development of antiviral strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Defective viral genome (DVG) is a truncated version of the full-length virus genome identified in most RNA viruses during infection. The synthesis of DVGs in coronavirus has been suggested; however, the fundamental characteristics of coronavirus DVGs in gene expression and pathogenesis have not been systematically analyzed., Methods: Nanopore direct RNA sequencing was used to investigate the characteristics of coronavirus DVGs in gene expression including reproducibility, abundance, species and genome structures for bovine coronavirus in cells, and for mouse hepatitis virus (MHV)-A59 (a mouse coronavirus) in cells and in mice. The MHV-A59 full-length genomic cDNAs (~ 31 kilobases) were in vitro constructed to experimentally validate the origin of coronavirus DVG. The synthesis of DVGs was also experimentally identified by RT-PCR followed by sequencing. In addition, the alterations of DVGs in amounts and species under different infection environments and selection pressures including the treatment of antiviral remdesivir and interferon were evaluated based on the banding patterns by RT-PCR., Results: The results are as follows: (i) the structures of DVGs are with diversity, (ii) DVGs are overall synthesized with moderate (MHV-A59 in cells) to high (BCoV in cells and MHV-A59 in mice) reproducibility under regular infection with the same virus inoculum, (iii) DVGs can be synthesized from the full-length coronavirus genome, (iv) the sequences flanking the recombination point of DVGs are AU-rich and thus may contribute to the recombination events during gene expression, (v) the species and amounts of DVG are altered under different infection environments, and (vi) the biological nature of DVGs between in vitro and in vivo is similar., Conclusions: The identified biological characteristics of coronavirus DVGs in terms of abundance, reproducibility, and variety extend the current model for coronavirus gene expression. In addition, the biological features of alterations in amounts and species of coronavirus DVGs under different infection environments may assist the coronavirus to adapt to the altered environments for virus fitness and may contribute to the coronavirus pathogenesis. Consequently, the unveiled biological features may assist the community to study the gene expression mechanisms of DVGs and their roles in pathogenesis, contributing to the development of antiviral strategy and public health., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Exposure to traffic-related air pollution consisting of particulate matter (PM) is associated with cognitive decline leading to Alzheimer's disease (AD). In this study, we sought to examine the neurotoxic effects of exposure to ultrafine PM and how it exacerbates neuronal loss and AD-like neuropathology in wildtype (WT) mice and a knock-in mouse model of AD (AppNL-G-F/+-KI) when the exposure occurs at a prepathologic stage or at a later age with the presence of neuropathology. AppNL-G-F/+-KI and WT mice were exposed to concentrated ultrafine PM from local ambient air in Irvine, California, for 12 weeks, starting at 3 or 9 months of age. Particulate matter-exposed animals received concentrated ultrafine PM up to 8 times above the ambient levels, whereas control animals were exposed to purified air. Particulate matter exposure resulted in a marked impairment of memory tasks in prepathologic AppNL-G-F/+-KI mice without measurable changes in amyloid-β pathology, synaptic degeneration, and neuroinflammation. At aged, both WT and AppNL-G-F/+-KI mice exposed to PM showed a significant memory impairment along with neuronal loss. In AppNL-G-F/+-KI mice, we also detected an increased amyloid-β buildup and potentially harmful glial activation including ferritin-positive microglia and C3-positive astrocytes. Such glial activation could promote the cascade of degenerative consequences in the brain. Our results suggest that exposure to PM impairs cognitive function at both ages while exacerbation of AD-related pathology and neuronal loss may depend on the stage of pathology, aging, and/or state of glial activation. Further studies will be required to unveil the neurotoxic role of glial activation activated by PM exposure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the effects of various demographic, structural, radiographic, and clinical factors on the prognosis of patients with medial compartmental knee osteoarthritis with varus deformity undergoing medial opening wedge high tibial osteotomy (HTO) in combination with bone marrow concentrate (BMC) injection., Methods: In this prospective study, 20 patients underwent medial opening wedge HTO in combination with BMC injection with 12 months of follow-up. The structural and radiographic outcomes were evaluated by femorotibial angle and posterior tibial slope angle. The clinical outcomes were evaluated by visual analogue scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and The Knee injury and Osteoarthritis Outcome Score (KOOS). Multivariate nonlinear mixed-effects models with asymptotic regressions were used to model the trajectory of symptom improvement., Results: Medial opening wedge HTO in combination with BMC corrected the malalignment of the knee and led to significant symptom relief. The improvement of clinical symptoms reached a plateau 6 months after the surgery. Greater symptom severity at baseline and lower Kellgren-Lawrance (KL) grades were correlated with better post-operative clinical outcomes. Body-Mass-Index (BMI), femorotibial angle, age, and sex may also play a role in influencing the extent of symptom relief., Conclusion: Symptom severity at baseline is important for prognosis prediction. In clinical practice, we suggest that the evaluation of clinical features and functional status of the patients be more emphasised., (© 2023. The Author(s).)

Tranexamic acid is an effective treatment to reduce blood loss. We performed a retrospective observational study to evaluate safety in unilateral total knee arthroplasty. We utilised Taiwan's national health insurance database to identify relevant patients and to retrieve information on peri-operative blood transfusions and tranexamic acid administration within 60 days of follow-up. We examined changes in the rate of transfusions and adverse events with respect to tranexamic acid administration using logistic regression. We observed a total of 226,719 knee arthroplasty cases during 2010-2019. Transfusion and tranexamic acid administration rates were 38.9% (88,258) and 42.9% (97,237), respectively. Tranexamic acid was associated with a 50% decrease in blood transfusions (RR: 0.50, 95%CI: 0.48-0.51). After propensity-score matching, tranexamic acid was not associated with pulmonary embolism; deep vein thromboembolism; artery vein thromboembolism; acute myocardial infarction; ischaemic stroke; or in-hospital mortality, but was significantly associated with acute kidney injury. Patients with existing chronic kidney disease suffered a high absolute risk of kidney injury irrespective of tranexamic acid administration (832 per 10,000, 95%CI 797-869). Tranexamic acid was also associated with surgical site infection. There was strong interaction between blood transfusion; tranexamic aid administration; and development of surgical site infection. In conclusion, tranexamic acid use was associated with decreased blood transfusion and was not associated with thromboembolic events. However, careful consideration is required before use in patients with pre-existing renal disease. Further, our observed interaction between patients given tranexamic acid who subsequently require transfusion requires careful consideration with respect to enhanced prophylaxis against surgical site infection., (© 2022 Association of Anaesthetists.)

The yellow crazy ant, Anoplolepis gracilipes is a widespread invasive ant that poses significant threats to local biodiversity. Yet, compared to other global invasive ant species such as the red imported fire ant ( Solenopsis invicta ) or the Argentine ant ( Linepithema humile ), little is known about the diversity of RNA viruses in the yellow crazy ant. In the current study, we generated a transcriptomic database for A . gracilipes using a high throughput sequencing approach to identify new RNA viruses and characterize their genomes. Four virus species assigned to Dicistroviridae , two to Iflaviridae , one to Polycipiviridae , and two unclassified Riboviria viruses were identified. Detailed genomic characterization was carried out on the polycipivirus and revealed that this virus comprises 11,644 nucleotides with six open reading frames. Phylogenetic analysis and pairwise amino acid identity comparison classified this virus into the genus Sopolycivirus under Polycipiviridae , which is tentatively named " Anoplolepis gracilipes virus 3 (AgrV-3)". Evolutionary analysis showed that AgrV-3 possesses a high level of genetic diversity and elevated mutation rate, combined with the common presence of multiple viral strains within single worker individuals, suggesting AgrV-3 likely evolves following the quasispecies model. A subsequent field survey placed the viral pathogen "hotspot" of A. gracilipes in the Southeast Asian region, a pattern consistent with the region being recognized as part of the ant's native range. Lastly, infection of multiple virus species seems prevalent across field colonies and may have been linked to the ant's social organization.

Background: Before 2010, guidelines recommended adenosine 6, 12, and a repeat dose of 12 mg for paroxysmal supraventricular tachycardia (PSVT). After 2010, these doses were reduced to two. This study aims to outline adenosine using trend from 2000 to 2012 in Taiwan emergency departments (EDs)., Methods: This was an ecological study. PSVT were drawn from one million individuals of the National Health Insurance Database. The χ 2 test was used to determine an association between different adenosine doses and other antiarrhythmic drugs (OADs), including verapamil, diltiazem, amiodarone, digoxin, and labetalol., Results: There were 3361 PSVT visits from 2000 to 2012; 834 (24.8%) did not receive an antiarrhythmic drug, and 2527 (75.2%) did, either adenosine with/without OADs or OADs alone. The use of an OAD was significantly different between the adenosine 6-18 mg and 19 + mg groups., Conclusions: Most PSVT episodes converted with adenosine within 18 mg, and the success conversion rate was 62.2%. It could be up to 65.2% if they received more. Of the patients who did not have their PSVT reverted with< 18 mg, 37.8% could have been successfully treated with more doses. The necessity of using the 3rd dose of adenosine is needed to be further explored., Competing Interests: Conflict of interest disclosure To the best of our knowledge, the named authors have no conflict of interest, financial or otherwise., (Copyright © 2021 College of Emergency Nursing Australasia. Published by Elsevier Ltd. All rights reserved.)

PURPOSE Intractable ascites (IA) is an uncommon but challenging complication after liver transplantation. Splenic artery embolization (SAE) modulates the splenic artery and regulates portal flow. This study aimed to evaluate the efficacy and safety of SAE using the Amplatzer vascular plug (AVP) versus coil embolization for post-living-donor liver transplantation (LDLT) IA. METHODS This retrospective study evaluated consecutive patients from 1 center who received LDLT (n=1410) between March 2006 and August 2019. The inclusion criteria for SAE were splenomegaly with IA after LDLT. RESULTS Totally 15 patients underwent SAE for post-LDLT IA. Eleven patients who received AVP embolization (age, 51.2 ± 15.1 years; range, 8-63 years; 5 men and 6 women) were compared with 4 patients receiving coil embolization (age, 30.8 ± 30.8 years; range, 1.5-63 years; 2 men and 2 women). AVP and coil embolization both significantly reduced portal vein hyperflow (plug/ coil; P <.001/.006) and decreased ascites volume (plug/coil; P <.003/.042). The benefits of AVP embolization included shorter procedure time (P =.029), significantly reduced splenic volume (P =.012), increased liver volume (P =.012), decreased spleen/liver ratio (P =.012), and improvement of pancytopenia (P =.008) due to secondary hypersplenism. No significant differences were found between the two groups in the length of hospital stay or complications such as splenic infarction, pancreatitis, or sepsis. CONCLUSION SAE using AVP and coil embolization provide effective and safe methods for managing patients with IA after LDLT. AVP embolization may be more efficient than coil embolization, providing more effective reduction of ascites volume and the advantages of shortened procedure time and improvement of hypersplenism.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a histopathological marker and risk factor for HCC recurrence. We integrated diffusion-weighted imaging (DWI) and magnetic resonance (MR) image findings of tumors into a scoring system for predicting MVI. In total, 228 HCC patients with pathologically confirmed MVI who underwent surgical resection or liver transplant between November 2012 and March 2021 were enrolled retrospectively. Patients were divided into a right liver lobe group ( n = 173, 75.9%) as the model dataset and a left liver lobe group ( n = 55, 24.1%) as the model validation dataset. Multivariate logistic regression identified two-segment involved tumor (Score: 1; OR: 3.14; 95% CI: 1.22 to 8.06; p = 0.017); ADC min ≤ 0.95 × 10 -3 mm 2 /s (Score: 2; OR: 10.88; 95% CI: 4.61 to 25.68; p = 0.000); and largest single tumor diameter ≥ 3 cm (Score: 1; OR: 5.05; 95% CI: 2.25 to 11.30; p = 0.000), as predictive factors for the scoring model. Among all patients, sensitivity was 89.66%, specificity 58.04%, positive predictive value 68.87%, and negative predictive value 84.41%. For validation of left lobe group, sensitivity was 80.64%, specificity 70.83%, positive predictive value 78.12%, and negative predictive value 73.91%. The scoring model using ADC min , largest tumor diameter, and two-segment involved tumor provides high sensitivity and negative predictive value in MVI prediction for use in routine functional MR.

Recovering and distinguishing different ionospheric layers and signals usually requires slow and complicated procedures. In this work, we construct and train five convolutional neural network (CNN) models: DeepLab, fully convolutional DenseNet24 (FC-DenseNet24), deep watershed transform (DWT), Mask R-CNN, and spatial attention-UNet (SA-UNet) for the recovery of ionograms. The performance of the models is evaluated by intersection over union (IoU). We collect and manually label 6131 ionograms, which are acquired from a low-latitude ionosonde in Taiwan. These ionograms are contaminated by strong quasi-static noise, with an average signal-to-noise ratio (SNR) equal to 1.4. Applying the five models to these noisy ionograms, we show that the models can recover useful signals with IoU > 0.6. The highest accuracy is achieved by SA-UNet. For signals with less than 15% of samples in the data set, they can be recovered by Mask R-CNN to some degree (IoU > 0.2). In addition to the number of samples, we identify and examine the effects of three factors: (1) SNR, (2) shape of signal, (3) overlapping of signals on the recovery accuracy of different models. Our results indicate that FC-DenseNet24, DWT, Mask R-CNN and SA-UNet are capable of identifying signals from very noisy ionograms (SNR < 1.4), overlapping signals can be well identified by DWT, Mask R-CNN and SA-UNet, and that more elongated signals are better identified by all models.

Background: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients., Methods: Retrospective review of 121 pediatric patients who underwent LDLT between May 1994 and December 2015 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and postoperative computed tomography images of the liver were reviewed, and portal vein complications were assessed., Results: Ninety-seven pediatric patients were included in the study, and 70 had portosystemic shunts before transplant. Thirty-three patients have portal systemic shunt (PSS) 6 months after transplant (mean [SD] shunt size, 4.59 [1.98] mm). Thirty-seven patients' portosystemic shunts closed spontaneously (mean [SD] shunt size, 3.14 [1.06] mm). Smaller PSSs tend to close spontaneously with a cutoff point of 3.35 mm by receiver operating characteristic curve (P = .01). Patients with PSS have more portal vein complications than those without PSS (44.3% vs 11.1%, P = .02). Among PSS recipients, patients with portal vein complications tend to have larger PSS size (mean [SD], 4.14 [1.96] mm vs 3.59 [1.48] mm), although the difference is not statistically significant (P = .19)., Conclusions: In pediatric patients, preoperative portosystemic shunts are significantly correlated with portal venous complications, some of which require minimal interventions after LDLT with good outcomes. Shunts larger than 3.35 mm tend to persist after transplant with increased portal venous complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Gadolinium-ethoxybenzyl-diethylene triamine pentaacetic acid (Gd-EOB-DTPA) is a newer magnetic resonance contrast that has the combined effect of conventional and liver-specific contrast. The use of Gd-EOB-DTPA may aid in management of patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplant (LDLT)., Materials and Methods: We retrospectively reviewed all HCC patients who received LDLT with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as part of a pretransplant evaluation between October 2012 and October 2016. The detection rate and impact on decision making were assessed between multidetector-row computed tomography (MDCT) and Gd-EOB-DTPA-enhanced MRI with pathology of the explanted liver being the reference standard., Results: We analyzed 25 patients with 80 nodules. Gd-EOB-DTPA-enhanced MRI showed superior detection rate for HCCs than MDCT (76.1% vs 35.8%). Among the 25 patients, 16 had additional HCCs detected by Gd-EOB-DTPA-enhanced MRI, which led to changes in therapeutic decisions in 11 patients. The recurrence rate and mortality rate were 4% (1 of 25). In the same period in our institution, the mortality rate was 13.9% (25 of 180) for those who did not receive Gd-EOB-DTPA-enhanced MRI as part of the pretransplant evaluation., Conclusions: The use of Gd-EOB-DTPA-enhanced MRI can aid in characterization of indeterminate nodules and detect more HCCs and thus more adequate downstaging and pretransplant neoadjuvant treatment ensue, which may lower the recurrence rate after LDLT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Since the advent of a new generation of inflow-sensitive inversion recovery (IFIR) technology, three-dimensional non-contrast-enhanced magnetic resonance angiography is being used to obtain hepatic vessel images without applying gadolinium contrast agent. The purpose of this study was to explore the diagnostic efficacy of non-contrast-enhanced magnetic resonance angiography (non-CE MRA), contrast-enhanced magnetic resonance angiography (CMRA), and computed tomography angiography (CTA) in the preoperative evaluation of living liver donors. Methods: A total of 43 liver donor candidates who were evaluated for living donor liver transplantation completed examinations. Donors' age, gender, renal function (eGFR), and previous CTA and imaging were recorded before non-CE MRA and CMRA. CTA images were used as the standard. Results: Five different classifications of hepatic artery patterns (types I, III, V, VI, VIII) and three different classifications of portal vein patterns (types I, II, and III) were identified among 43 candidates. The pretransplant vascular anatomy was well identified using combined non-CE MRA and CMRA of hepatic arteries (100%), PVs (98%), and hepatic veins (100%) compared with CTA images. Non-CE MRA images had significantly stronger contrast signal intensity of portal veins ( p < 0.01) and hepatic veins ( p < 0.01) than CMRA. No differences were found in signal intensity of the hepatic artery between non-CE MRA and CMRA. Conclusion: Combined non-CE MRA and CMRA demonstrate comparable diagnostic ability to CTA and provide enhanced biliary anatomy information that assures optimum donor safety.

Interstellar dust particles were discovered in situ, in the solar system, with the Ulysses mission's dust detector in 1992. Ever since, more interstellar dust particles have been measured inside the solar system by various missions, providing insight into not only the composition of such far-away visitors, but also in their dynamics and interaction with the heliosphere. The dynamics of interstellar (and interplanetary) dust in the solar/stellar systems depend on the dust properties and also on the space environment, in particular on the heliospheric/astrospheric plasma, and the embedded time-variable magnetic fields, via Lorentz forces. Also, solar radiation pressure filters out dust particles depending on their composition. Charge exchanges between the dust and the ambient plasma occur, and pick-up ions can be created. The role of the dust for the physics of the heliosphere and astrospheres is fairly unexplored, but an important and a rapidly growing topic of investigation. This review paper gives an overview of dust processes in heliospheric and astrospheric environments, with its resulting dynamics and consequences. It discusses theoretical modeling, and reviews in situ measurements and remote sensing of dust in and near our heliosphere and astrospheres, with the latter being a newly emerging field of science. Finally, it summarizes the open questions in the field., Competing Interests: Competing InterestsThe authors declare they have no conflicts of interest., (© The Author(s) 2022.)

Purpose: Composite cyclin-dependent kinase (CDK) inhibition has shown potential as a treatment for hepatocellular carcinoma (HCC) in preclinical studies. We tested whether the specific inhibition of CDK9 was effective against HCC., Methods: The effects of two specific CDK9 inhibitors, BAY1143572 and AZD4573, in HCC cell lines were examined. We tested the in vivo efficacy of CDK9 inhibition in mouse xenograft models of HuH7 human HCC cells and in an orthotopic model of BNL mouse HCC cells. Overexpression and knockdown of CDK9 were performed to confirm the efficacy of CDK9 inhibition., Results: CDK9 inhibitors exhibited potent antiproliferative activities in HCC cells regardless of the levels of c-myc expression while inhibiting the downstream signals of CDK9, such as the phosphorylation of RNA polymerase II. These 2 CDK9 inhibitors induced apoptosis in HCC cells and reduced the expression of antiapoptotic proteins such as myeloid cell leukemia-1 and survivin. In the xenograft studies, mice receiving either CDK9 inhibitor exhibited significantly slower tumor growth than did the mice receiving vehicles. In the orthotopic model, the HCC growth in mice receiving a CDK9 inhibitor also tended to be slower than that in the control group. Overexpression of CDK9 in HuH7 cells reduced the efficacy of both CDK9 inhibitors. Knockdown of CDK9 expression reduced the proliferative activities of HCC cells., Conclusion: We demonstrated the in vitro and in vivo activity of CDK9 inhibition on multiple HCC cell lines. Our data support further clinical development of CDK9 inhibitors as a treatment for HCC., (© 2022 S. Karger AG, Basel.)

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.

Despite technological and immunological innovations, living-donor liver transplant (LDLT) recipients still face substantial risk of postoperative complications. Sarcopenia is being recognized more and more as a biomarker that correlates with poor outcomes in surgical patients. The purpose of this study was to evaluate the relationship between sarcopenia and significant surgical complications in LDLT recipients. This retrospective review included patients who had received LDLT at our institute from 2005 to 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. ROC curve analysis was used to determine the ability of PMI to predict postoperative complications. Correlations between major postoperative complications and sarcopenia were evaluated using regression analysis. A total of 271 LDLT recipients were included. No significant differences were found between PMI and major postoperative complications in male patients. Female recipients with major postoperative complications had significantly lower mean PMI values (P = 0.028), and the PMI cut-off value was 2.63 cm 2 /m 2 . Postoperative massive pleural effusion requiring pigtail drainage occurred more frequently in the sarcopenia group than in the non-sarcopenia group (P = 0.003). 1-, 3-, 5- and 10-year overall survival rates in female were significantly poorer in the sarcopenia group (n = 14) compared with the non-sarcopenia group (n = 108), at 92.9% versus 97.2%, 85.7% versus 95.4%, 85.7% versus 92.5% and 70.1 versus 82.0%, respectively (P = 0.041) and 94.6%, 89.9%, 85.9% and 78.5% in male patients. Sarcopenia is associated with a significantly higher risk of major postoperative complications in females. PMI and sarcopenia together are predictive of major postoperative complications and survival rates in female LDLT recipients., (© 2021. The Author(s).)

The technique of active ionospheric sounding by ionosondes requires sophisticated methods for the recovery of experimental data on ionograms. In this work, we applied an advanced algorithm of deep learning for the identification and classification of signals from different ionospheric layers. We collected a dataset of 6131 manually labeled ionograms acquired from low-latitude ionosondes in Taiwan. In the ionograms, we distinguished 11 different classes of the signals according to their ionospheric layers. We developed an artificial neural network, FC-DenseNet24, based on the FC-DenseNet convolutional neural network. We also developed a double-filtering algorithm to reduce incorrectly classified signals. That made it possible to successfully recover the sporadic E layer and the F2 layer from highly noise-contaminated ionograms whose mean signal-to-noise ratio was low, SNR = 1.43. The Intersection over Union (IoU) of the recovery of these two signal classes was greater than 0.6, which was higher than the previous models reported. We also identified three factors that can lower the recovery accuracy: (1) smaller statistics of samples; (2) mixing and overlapping of different signals; (3) the compact shape of signals.

Background & Problem: The need to use an indwelling nasogastric tube, urinary catheter, or tracheostomy tube (the so-called "three tubes") because of illness or prolonged bedrest is increasing. The functions and effectiveness of these tubes may be maintained only with correct care. Improper care, slippage, obstruction, or infection may in severe cases cause septic shock or even death., Purpose: To increase the completeness of the reverse demonstration of three tubes care instructions by primary caregivers to further improve related care quality., Resolution: Between February 10th and March 31st, 2019, the completeness rates of reverse demonstration of nasogastric tube, urinary catheter, and tracheostomy tube care instructions among the primary caregivers participating in this study were shown to be low, at 42.5%, 38%, and 58.3%, respectively. The plausible causes were: 1. Human: Poor communication, forgetting the care steps, having no time for learning, and fear of performing nasogastric tube rotation; 2. Instrument: Lack of graphic demonstrations in health education materials; 3. Policy: Lack of standards and auditing. The implemented intervention involved creating innovative health-education instruments, videos and flash cards about three tubes care in multiple languages, and straps for holding the urinary catheter and developing standards and an auditing system for the reverse demonstration of three tube care instructions by primary caregivers., Results: The completeness rates for the reverse demonstration of nasogastric tube, urinary catheter, and tracheostomy tube care instructions among the primary caregivers improved to 97.3%, 96.3%, and 95%, respectively., Conclusions: Using the innovative health-education aids and improvements introduced in this study, the ability of primary caregivers to correctly perform the care steps should improve significantly.

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.

Effective clearance of neurotoxic amyloid-beta (Aβ) from the brain is a critical process to prevent Alzheimer's disease (AD). One major clearance mechanism is Aβ transcytosis mediated by low-density lipoprotein receptor-related protein 1 (LRP1) in capillary endothelial cells. A marked loss of endothelial LRP1 is found in AD brains and is believed to significantly impair Aβ clearance. Recently, we demonstrated that pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, significantly down-regulated LRP1 in human primary microvascular endothelial cells (MVECs). In this study, we sought to determine the underlying molecular mechanism by which IL-1β led to LRP1 loss in MVECs. Reduced LRP1 protein and transcript were detected up to 24 h post-exposure and returned to the baseline levels after 48 h post-exposure with 1 ng/ml IL-1β. This reduction was in part mediated by microRNA-205-5p, -200b-3p, and -200c-3p, as these microRNAs were concomitantly upregulated in MVECs exposed to IL-1β. Synthetic microRNA-205-5p, -200b-3p, and -200c-3p mimics recapitulated LRP1 loss in MVECs without IL-1β, and their synthetic antagomirs effectively reversed IL-1β-mediated LRP1 loss. Importantly, we found that the expression of these three microRNAs was controlled by NF-κB as pharmacological NF-κB inhibitor, BMS-345541, inhibited the IL-1β-mediated upregulation of these microRNAs and rescued LRP1 expression. siRNA-mediated silencing of IκB in MVECs elevated microRNA-200b-3p and decreased LRP1 transcript, partially confirming our overall findings. In conclusion, our study provides a mechanism by which pro-inflammatory IL-1β instigates the suppression of LRP1 expression in MVECs. Our findings could implicate spatiotemporal loss of LRP1 and impairment of the LRP1-mediated clearance mechanism by endothelial cells., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Copper (Cu) is an essential metal mediating a variety of vital biological reactions with its redox property. Its dyshomeostasis has been associated with accelerated cognitive decline and neurodegenerative disorders, such as Alzheimer's disease (AD). However, underlying neurotoxic mechanisms elicited by dysregulated Cu remain largely elusive. We and others previously demonstrated that exposure to Cu in drinking water significantly exacerbated pathological hallmarks of AD and pro-inflammatory activation of microglia, coupled with impaired phagocytic capacity, in mouse models of AD., Methods: In the present study, we extended our investigation to evaluate whether chronic Cu exposure to wild-type (WT) and J20 mouse model of AD perturbs homeostatic dynamics of microglia and contributes to accelerated transformation of microglia towards degenerative phenotypes that are closely associated with neurodegeneration. We further looked for evidence of alterations in the microglial morphology and spatial memory of the Cu-exposed mice to assess the extent of the Cu toxicity., Results: We find that chronic Cu exposure to pre-pathological J20 mice upregulates the translation of degenerative genes and represses homeostatic genes within microglia even in the absence amyloid-beta plaques. We also observe similar expression signatures in Cu-exposed WT mice, suggesting that excess Cu exposure alone could lead to perturbed microglial homeostatic phenotypes and contribute to accelerated cognitive decline., Conclusion: Our findings highlight the risk of chronic Cu exposure on cognitive decline and altered microglia activation towards degenerative phenotypes. These changes may represent one of the key mechanisms linking Cu exposure or its dyshomeostasis to an increased risk for AD., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Spillover of honey bee viruses have posed a significant threat to pollination services, triggering substantial effort in determining the host range of the viruses as an attempt to understand the transmission dynamics. Previous studies have reported infection of honey bee viruses in ants, raising the concern of ants serving as a reservoir host. Most of these studies, however, are restricted to a single, local ant population. We assessed the status (geographical distribution/prevalence/viral replication) and phylogenetic relationships of honey bee viruses in ants across the Asia-Pacific region, using deformed wing virus (DWV) and two widespread invasive ants, Paratrechina longicornis and Anoplolepis gracilipes , as the study system. DWV was detected in both ant species, with differential geographical distribution patterns and prevenance levels between them. These metrics, however, are consistent across the geographical range of the same ant species. Active replication was only evident in P . longicornis . We also showed that ant-associated DWV is genetically similar to that isolated from Asian populations of honey bees, suggesting that local acquisition of DWV by the invasive ants may have been common at least in some of our sampled regions. Transmission efficiency of DWV to local arthropods mediated by ant, however, may vary across ant species.

We report two novel RNA viruses from yellow crazy ants, (Anoplolepis gracilipes) detected using next-generation sequencing. The complete genome sequences of the two viruses were 10,662 and 8,238 nucleotides in length, respectively, with both possessing two open reading frames with three conserved protein domains. The genome organization is characteristic of members of the genus Triatovirus in the family Dicistroviridae. The two novel viruses were tentatively named "Anoplolepis gracilipes virus 1" and "Anoplolepis gracilipes virus 2" (AgrV-1 and AgrV-2). Phylogenetic analyses based on amino acid sequences of the non-structural polyprotein (ORF1) suggest that the two viruses are triatovirus-like viruses. This is the first report on the discovery of novel triatovirus-like viruses in yellow crazy ants with a description of their genome structure (two ORFs and conserved domains of RNA helicase, RNA-dependent RNA polymerase, and capsid protein), complete sequences, and viral prevalence across the Asia-Pacific region.

Purpose: The purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres., Materials and Methods: Between October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-μm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile., Results: Median follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff)., Conclusions: Tandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Early hepatic artery thrombosis (eHAT) is a severe arterial complication leading to biliary complications and graft failure in living donor liver transplantation (LDLT). This study sought to early identify the abnormal waveforms of eHAT by using intensive Doppler ultrasonography (DUS) after LDLT and to assess the clinical outcome in these eHAT patients. MATERIAL AND METHODS DUS for 419 adult LDLT recipients was performed twice after vascular anastomosis during liver transplantation and once a day at the bedside for at least 2 weeks. RESULTS Nine adult LDLT recipients with eHAT were identified by using bedside DUS with subsequent computed tomography angiography (CTA). All eHAT cases were noted in the first 2 weeks. Five patients with CTA findings of partial thrombus with the small visualized intrahepatic hepatic artery (HA) were treated with intravenous thrombolysis (IVT) (medical group). Another 4 patients with CTA findings of extrahepatic HA occlusion and nonvisualization of intrahepatic HAs were treated by arterial re-anastomosis (surgical group). The prevalence of long-term non-anastomotic biliary strictures was 33.3% in the surgical group. Intensive post-LDLT DUS is a convenient and sensitive tool for eHAT detection. CONCLUSIONS Subsequent CTA gives valid information on occluded arteries and associated findings, which impact decision-making and are correlated with patient outcome. Our protocol of DUS has high sensitivity and diagnostic accuracy for use in in eHAT patients with partial occlusion, and it can be applied for IVT treatment, avoiding the need for reoperation and preventing long-term biliary complications.

Background: The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy., Methods: This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4 weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors., Results: At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24 mm 2 /s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10 -3  mm 2 /s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10 -3 ) and non-responsive (17.2 ± 4.9 × 10 -3 ) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001)., Conclusions: Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.

Self-avoidance is a conserved mechanism that prevents crossover between sister dendrites from the same neuron, ensuring proper functioning of the neuronal circuits. Several adhesion molecules are known to be important for dendrite self-avoidance, but the underlying molecular mechanisms are incompletely defined. Here, we show that FMI-1/Flamingo, an atypical cadherin, is required autonomously for self-avoidance in the multidendritic PVD neuron of Caenorhabditis elegans The fmi-1 mutant shows increased crossover between sister PVD dendrites. Our genetic analysis suggests that FMI-1 promotes transient F-actin assembly at the tips of contacting sister dendrites to facilitate their efficient retraction during self-avoidance events, probably by interacting with WSP-1/N-WASP. Mutations of vang-1 , which encodes the planar cell polarity protein Vangl2 previously shown to inhibit F-actin assembly, suppress self-avoidance defects of the fmi-1 mutant. FMI-1 downregulates VANG-1 levels probably through forming protein complexes. Our study identifies molecular links between Flamingo and the F-actin cytoskeleton that facilitate efficient dendrite self-avoidance., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Purpose: The aim of this study was to compare the metabolic load between adaptive support ventilation (ASV) and pressure support ventilation (PSV) modes in critically ill patients., Methods: Sequential 20 min ventilation by PSV followed by 20 min ASV in critically ill patients was assessed. ASV was set for full support, i.e., with the minute volume control set at the same level as the minute volume observed during PSV. The trial started from PSV 8 cmH 2 O and continued with high (PSV 12 cmH 2 O) to low (PSV 0) conditions or low to high conditions, in random order. The oxygen consumption (VO 2 ), production of carbon dioxide (VCO 2 ), and energy expenditure (EE) were measured by indirect calorimetry (IC)., Results: Twenty-four patients with critical illness participated in the study. Comparing with the PSV mode, the EE in the ASV mode was lower in the level of PSV 0 cmH 2 O (1069 ± 73 vs. 1425 ± 76 kcal), PS 8 cmH 2 O (1116 ± 70 vs. 1284 ± 61 kcal), and PS 12 cmH 2 O (1017 ± 70 vs. 1169 ± 58 kcal) ( p < 0.05). The VO 2 , VCO 2 , and P0.1 in PSV were significantly higher than those in ASV ( p < 0.05). The VO 2 , VCO 2 , and P0.1 in PSV were significantly higher than those in ASV (., Conclusion: In patients with critical illness, the application of ASV set for full support was associated with a lower metabolic load and respiratory drive than in any of the studied PSV conditions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yen-Huey Chen et al.)

The recent discovery of multiple viruses in ants, along with the widespread infection of their hosts across geographic ranges, provides an excellent opportunity to test whether viral prevalence in the field is associated with the complexity of social interactions in the ant population. In this study, we examined whether the association exists between the field prevalence of a virus and the intercolonial aggression of its ant host, using the yellow crazy ant ( Anoplolepis gracilipes ) and its natural viral pathogen (TR44839 virus) as a model system. We delimitated the colony boundary and composition of A . gracilipes in a total of 12 study sites in Japan (Okinawa), Taiwan, and Malaysia (Penang), through intercolonial aggression assay. The spatial distribution and prevalence level of the virus was then mapped for each site. The virus occurred at a high prevalence in the surveyed colonies of Okinawa and Taiwan (100% infection rate across all sites), whereas virus prevalence was variable (30%-100%) or none (0%) at the sites in Penang. Coincidentally, colonies in Okinawa and Taiwan displayed a weak intercolonial boundary, as aggression between colonies is generally low or moderate. Contrastingly, sites in Penang were found to harbor a high proportion of mutually aggressive colonies, a pattern potentially indicative of complex colony composition. Our statistical analyses further confirmed the observed correlation, implying that intercolonial interactions likely contribute as one of the effective facilitators of/barriers to virus prevalence in the field population of this ant species., Competing Interests: The authors declare no conflict of interest.

Background: Tumor recurrence is the major risk factor affecting post-transplant survival. In this retrospective study, we evaluate the prognostic values of magnetic resonance (MR) diffusion-weighted imaging (DWI) in liver transplantation for hepatocellular carcinoma (HCC)., Methods: From April 2014 to September 2016, 106 HCC patients receiving living donor liver transplantation (LDLT) were enrolled. Nine patients were excluded due to postoperative death within 3 months and incomplete imaging data. The association between tumor recurrence, explant pathologic findings, and DWI parameters was analyzed (tumor-to-liver diffusion weighted imaging ratio, DWI T/L ; apparent diffusion coefficients, ADC). The survival probability was calculated using the Kaplan-Meier method., Results: Sixteen of 97 patients (16%) developed tumor recurrence during the follow-up period (median of 40.9 months; range 5.2-56.5). In those with no viable tumor (n = 65) on pretransplant imaging, recurrence occurred only in 5 (7.6%) patients. Low minimum ADC values (p = 0.001), unfavorable tumor histopathology (p <  0.001) and the presence of microvascular invasion (p <  0.001) were risk factors for tumor recurrence, while ADC mean (p = 0.111) and DWI T/L (p = 0.093) showed no significant difference between the groups. An ADC min  ≤ 0.88 × 10 - 3  mm 2 /s was an independent factor associated with worse three-year recurrence-free survival (94.4% vs. 23.8%) and overall survival rates (100% vs. 38.6%)., Conclusions: Quantitative measurement of ADC min is a promising prognostic indicator for predicting tumor recurrence after liver transplantation.