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This paper is concerned with when to implement preventive maintenance (PM) and replacement for a repairable `single-unit' system in use. Under the main assumption that a `single-unit' system gradually deteriorates with time, a sequential method is proposed to determine an optimal PM and replacement strategy for the system based on minimising expected loss rate. According to this method, PM epochs are determined one after the other, and consequently we can make use of all previous information on the operation process of the system. Also the replacement epoch depends on the effective age of the system. A numerical example shows that the sequential method can be used to solve the PM and replacement problem of a `single-unit' system efficiently. Some properties of the loss functions W ([[bar]L.sub.n], [[bar]b.sub.n]) and [[bar]W.sub.r](N) with respect to PM and replacement respectively are discussed in the appendix. Keywords: corrective maintenance; preventive maintenance; replacement; sequential method; loss

Background: Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT-1 and RRM1 expression in resected pancreatic cancer.Methods: Eighty-four patients who underwent pancreaticoduodenectomy from 2000 to 2005 were included in this study. Patients were followed for a median of 60 months (range, 44-110). Total RNA was isolated from macrodissected paraffin-embedded tumors. hENT-1 and RRM1 expression levels in tumors were evaluated by quantitative reverse transcription-polymerase chain reaction (QRT-PCR), normalized to 2 reference genes, and expressed as ΔCt (low ΔCt means high expression). Univariate and multivariable prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified via Cox proportional hazards analysis.Results: Univariate analysis identified hENT-1, overall stage, lymphovascular invasion, perineural invasion, and adjuvant therapy as prognostic factors for both PFS and OS. Multivariate analysis confirmed the association of low expression of hENT-1 (ΔCt > 0.2027) (P = .007), perineural invasion (P = .021), and lack of adjuvant treatment (P < 0.001) with worse OS. Multivariate analysis also confirmed the association of low expression of hENT-1 (ΔCt > 0.5391) with worse PFS (P = .016) in addition to overall stage (P = .013), perineural invasion (P = .042), and lack of adjuvant treatment (hazard ratio 2.31, P = .029). RRM1 expression was not associated with OS or PFS in the current cohort.Conclusions: Low expression of hENT-1 was associated with worse OS and PFS in patients with resected pancreatic adenocarcinoma independent of gemcitabine therapy. [ABSTRACT FROM AUTHOR]

When applying for patents, companies should consider performing patent portfolios as a means of integrating their patent strategy to shape their overall business strategy. This is an important issue for any company in pursuit of enhanced operational performance because the whole raison d'être behind the application of patents is the anticipation of achieving maximum competitive advantage. A prerequisite for such a company is a decision analysis model of patent portfolios because this has the added advantage of being readily applicable to the evaluation of the quality of its competitors' portfolios; thus, by understanding both itself and its competitors, a company can attain a superior position. To demonstrate this, we examine patent priority networks (PPNs) formed through patent family members and claimed priority patents, performing a model of patent portfolio analysis and then going on to determine the algorithms. We suggest that information retrieved from this network can provide a useful reference tool for decision-making by company CEOs,CTOs,R&Dmanagers,and intellectual property managers. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of virtual reality-based infrared pupillometry (VIP) to detect individuals suffering long COVID., Design: Prospective, case-control cross-sectional study., Participants: Participants aged 20-60 were recruited from a community eye screening programme., Methods: Pupillary Light Responses (PLR) were recorded in response to 3 intensities of light stimuli (L6, L7 and L8) using a virtual reality head-mount display (VR-HMD). 9 PLR waveform features for each stimulus, were extracted by 2 masked observers and statistically analyzed. We also use various methods on the whole PLR waveform including trained, validated and tested (6:3:1) by machine learning models including Multi-layer Perceptron, Support Vector Machine, K-nearest Neighbors, Logistic Regression, Decision Tree, Random Forest and Long Short-Term Memory (LSTM) models for two and three-class classification into long-COVID (LCVD), post-COVID (PCVD) or control., Main Outcome Measures: Accuracies/AUC of individual or combination of PLR features and ML models using PLR features or whole pupillometric waveform., Results: PLR from a total of 185 subjects including 112 LCVD, 44 PCVD and 29 age/sex-matched controls were analysed. Models examined the independent effects of age and sex. Constriction Time(CT) after the brightest stimulus(L8) is significantly associated with LCVD status(two-way ANOVA, false discovery rate(FDR)<0.001; multinominal logistic regression, FDR<0.05). The overall accuracy/AUC of CT-L8 alone in differentiating LCVD from control or from PCVD were 0.7808/0.8711 and 0.8654/0.8140 respectively. Using cross-validated backward stepwise variable selection, CT-L8, CT-L6, Constriction Velocity(CV)-L6 were most useful to detect LCVD while CV-L8 for PCVD from other groups. The accuracy/AUC of selected features were 0.8000/0.9000 (control versus LCVD) and 0.9062/0.9710 (PCVD versus LCVD), better than when all 27 pupillometric features were combined. An LSTM model analyzing whole pupillometric waveform achieved the highest accuracy/AUC at 0.9375/1.000 in differentiating LCVD from PCVD and a slightly lower accuracy of 0.7838 for three-class classification (LCVD-PCVD-control)., Conclusions: We reported, for the first time, specific pupillometric signatures in differentiating LCVD from PCVD or control subjects using a VR-HMD. Combining statistical methods to identify specific pupillometric features and ML algorithms to analyse the performance further enhance the performance of VIP as a non-intrusive, low-cost, portable and objective method to detect and monitor long COVID., (Copyright © 2024. Published by Elsevier Inc.)

Ecological functions of coastal wetlands are closely linked to microbiome that is affected by anthropogenic pollution, but related systematic research is rare. This study explored microbial community and physicochemical characteristics of sediments in three habitats, mudflat, mangrove and inter-tidal shrimp ponds (gei wai), in a Ramsar using 16S amplicon sequencing. Proteobacteria was the most abundant and Vibrio was detected in all habitats. Microbial diversity in mangrove is higher than mudflat, with gei wai in between. Microbial functions predicted by PICRUSt revealed prevalence of carbohydrate and amino acid metabolism, with enrichment of nitrogen metabolism in mangrove habitat. Gene annotation identified approximately 800 intrinsic antibiotic resistance genes (iARGs) and dominant mechanism was antibiotic inactivation. Variation partitioning analysis indicated sediment characteristics together with antibiotics and heavy metals shaped microbiomes and iARGs composition in sediments. This study offers insights into variations of sediment microbial diversity, function and iARGs among different habitats in protected wetlands., Competing Interests: Declaration of competing interest The authors declare that there are no known financial and personal relationships with other people or organizations that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hong Kong, renowned for its densely packed urban areas, poses unique challenges for understanding the effects of buildings on local meteorological conditions. To address this, the Hong Kong Observatory has started building a network of urban meteorological monitoring stations since 2017 for monitoring, analysing and studying urban microclimate. This paper presents an observational and numerical study focusing on wind measurements obtained from wind sensors installed on two smart lampposts in Tsim Sha Tsui, a major urban area in Hong Kong. Two representative high wind conditions in Hong Kong, Super Typhoon Saola in 2023 and a strong monsoon case characterized by prevailing easterly winds, are considered. With the use of high resolution computational fluid dynamic simulations, major features of actual observations can be reproduced. This suggests that district scale or even street scale weather services could be possible in the future with sufficient computational power., 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. Published by Elsevier Ltd.)

Objectives: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population., Methods: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021., Results: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation ( P  < 0.0001), a higher male-to-female ratio ( P  = 0.0045) and a higher age of disease onset ( P  = 0.0092). Family history of thyroid disease was more common in TED patients ( P  = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally ( P  < 0.0001), and they have a larger difference in MRD1 ( P  < 0.0001), and extraocular motility ( P  < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients ( P  = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar., Conclusions: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We have investigated the function of inositol hexakisphosphate (IP6) and inositol pentakisphosphate (IP5) in the replication of murine leukemia virus (MLV). While IP6 is known to be critical for the life cycle of HIV-1, its significance in MLV remains unexplored. We find that IP6 is indeed important for MLV replication. It significantly enhances endogenous reverse transcription (ERT) in MLV. Additionally, a pelleting-based assay reveals that IP6 can stabilize MLV cores, thereby facilitating ERT. We find that IP5 and IP6 are packaged in MLV particles. However, unlike HIV-1, MLV depends upon the presence of IP6 and IP5 in target cells for successful infection. This IP6/5 requirement for infection is reflected in impaired reverse transcription observed in IP6/5-deficient cell lines. In summary, our findings demonstrate the importance of capsid stabilization by IP6/5 in the replication of diverse retroviruses; we suggest possible reasons for the differences from HIV-1 that we observed in MLV.IMPORTANCEInositol hexakisphosphate (IP6) is crucial for the assembly and replication of HIV-1. IP6 is packaged in HIV-1 particles and stabilizes the viral core enabling it to synthesize viral DNA early in viral infection. While its importance for HIV-1 is well established, its significance for other retroviruses is unknown. Here we report the role of IP6 in the gammaretrovirus, murine leukemia virus (MLV). We found that like HIV-1, MLV packages IP6, and as in HIV-1, IP6 stabilizes the MLV core thus promoting reverse transcription. Interestingly, we discovered a key difference in the role of IP6 in MLV versus HIV-1: while HIV-1 is not dependent upon IP6 levels in target cells, MLV replication is significantly reduced in IP6-deficient cell lines. We suggest that this difference in IP6 requirements reflects key differences between HIV-1 and MLV replication., Competing Interests: The authors declare no conflict of interest.

The objective of this study is to create a planar solar light absorber that exhibits exceptional absorption characteristics spanning from visible light to infrared across an ultra-wide spectral range. The eight layered structures of the absorber, from top to bottom, consisted of Al 2 O 3 , Ti, Al 2 O 3 , Ti, Al 2 O 3 , Ni, Al 2 O 3 , and Al. The COMSOL Multiphysics ® simulation software (version 6.0) was utilized to construct the absorber model and perform simulation analyses. The first significant finding of this study is that as compared to absorbers featuring seven-layered structures (excluding the top Al 2 O 3 layer) or using TiO 2 or SiO 2 layers as substituted for Al 2 O 3 layer, the presence of the top Al 2 O 3 layer demonstrated superior anti-reflection properties. Another noteworthy finding was that the top Al 2 O 3 layer provided better impedance matching compared to scenarios where it was absent or replaced with TiO 2 or SiO 2 layers, enhancing the absorber's overall efficiency. Consequently, across the ultra-wideband spectrum spanning 350 to 1970 nm, the average absorptivity reached an impressive 96.76%. One significant novelty of this study was the utilization of various top-layer materials to assess the absorption and reflection spectra, along with the optical-impedance-matching properties of the designed absorber. Another notable contribution was the successful implementation of evaporation techniques for depositing and manufacturing this optimized absorber. A further innovation involved the use of transmission electron microscopy to observe the thickness of each deposition layer. Subsequently, the simulated and calculated absorption spectra of solar energy across the AM1.5 spectrum for both the designed and fabricated absorbers were compared, demonstrating a match between the measured and simulated results.

Objective: The aim of the work described here was to determine whether 3-D ultrasound can provide results comparable to those of conventional X-ray examination in assessing curve progression in patients with adolescent idiopathic scoliosis (AIS)., Methods: One hundred thirty-six participants with AIS (42 males and 94 females; age range: 10-18 y, mean age: 14.1 ± 1.9 y) with scoliosis of different severity (Cobb angle range: 10º- 85º, mean: of 24.3 ± 14.4º) were included. Each participant underwent biplanar low-dose X-ray EOS and 3-D ultrasound system scanning with the same posture on the same date. Participants underwent the second assessment at routine clinical follow-up. Manual measurements of scoliotic curvature on ultrasound coronal projection images and posterior-anterior radiographs were expressed as the ultrasound curve angle (UCA) and radiographic Cobb angle (RCA), respectively. RCA and UCA increments ≥5º represented a scoliosis progression detected by X-ray assessment and 3-D ultrasound assessment, respectively., Results: The sensitivity and specificity of UCA measurement in detecting scoliosis progression were 0.93 and 0.90, respectively. The negative likelihood ratio of the diagnostic test for scoliosis progression by the 3-D ultrasound imaging system was 0.08., Conclusion: The 3-D ultrasound imaging method is a valid technique for detecting coronal curve progression as compared with conventional radiography in follow-up of AIS. Substituting conventional radiography with 3-D ultrasound is effective in reducing the radiation dose to which AIS patients are exposed during their follow-up examinations., Competing Interests: Conflict of interest Y.P.Z. reports his role as a consultant to Telefield Medical Imaging Limited for the development of Scolioscan, outside the submitted work, and is the inventor of a number of patents related to 3-D ultrasound imaging for scoliosis, which has been licensed to Telefield Medical Imaging Limited through Hong Kong Polytechnic University. He is also a director and shareholder of this company. R.M.C. is the clinical advisor of Telefield Medical Imaging Limited. All of the remaining authors have no conflicts of interest relevant to this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, we show that mutations unique to Omicron Spike enable enhanced entry into nasal tissue. Unlike earlier variants of SARS-CoV-2, our findings suggest that Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. Furthermore, we demonstrate that this entry pathway unlocked by Omicron Spike enables evasion from constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Centralized particle swarm optimization (PSO) does not fully exploit the potential of distributed or parallel computing and suffers from single-point-of-failure. Particularly, each particle in PSO comprises a potential solution (e.g., traveling route and neural network model parameters) which is essentially viewed as private data. Unfortunately, previously neither centralized nor distributed PSO algorithms fail to protect privacy effectively. Inspired by secure multiparty computation and multiagent system, this article proposes a privacy-preserving multiagent PSO algorithm (called PriMPSO) to protect each particle's data and enable private data sharing in a privacy-preserving manner. The goal of PriMPSO is to protect each particle's data in a distributed computing paradigm via existing PSO algorithms with competitive performance. Specifically, each particle is executed by an independent agent with its own data, and all agents jointly perform global optimization without sacrificing any particle's data. Thorough investigations show that selecting an exemplar from all particles and updating particles through the exemplar are critical operations for PSO algorithms. To this end, this article designs a privacy-preserving exemplar selection algorithm and a privacy-preserving triple computation protocol to select exemplars and update particles, respectively. Strict privacy analyses and extensive experiments on a benchmark and a realistic task confirm that PriMPSO not only protects particles' privacy but also has uniform convergence performance with the existing PSO algorithm in approximating an optimal solution.

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first functional global midnolin knockout mouse model. Although the overwhelming majority of global homozygous midnolin knockout mice demonstrated embryonic lethality, heterozygous knockout mice were observed to be similar to wild-type mice in their viability and were used to determine the effect of reduced midnolin expression on NAFLD. We found that global heterozygous midnolin knockout attenuated the severity of NAFLD in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism. Collectively, our results support a role for midnolin in regulating cholesterol/lipid metabolism in the liver. Thus, midnolin may represent a novel therapeutic target for NAFLD. Finally, our observation that midnolin was essential for survival underscores the broad importance of this gene beyond its role in liver biology. NEW & NOTEWORTHY We have developed and now report on the first functional global midnolin knockout mouse model. We found that global heterozygous midnolin knockout attenuated the severity of nonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.

The host proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce infectivity when incorporated into the viral envelope. The HIV-1 accessory protein Nef abrogates incorporation of SERINCs via binding to intracellular loop 4 (ICL4). Here, we determine cryoEM maps of full-length human SERINC3 and an ICL4 deletion construct, which reveal that hSERINC3 is comprised of two α-helical bundles connected by a ~ 40-residue, highly tilted, "crossmember" helix. The design resembles non-ATP-dependent lipid transporters. Consistently, purified hSERINCs reconstituted into proteoliposomes induce flipping of phosphatidylserine (PS), phosphatidylethanolamine and phosphatidylcholine. Furthermore, SERINC3, SERINC5 and the scramblase TMEM16F expose PS on the surface of HIV-1 and reduce infectivity, with similar results in MLV. SERINC effects in HIV-1 and MLV are counteracted by Nef and GlycoGag, respectively. Our results demonstrate that SERINCs are membrane transporters that flip lipids, resulting in a loss of membrane asymmetry that is strongly correlated with changes in Env conformation and loss of infectivity., (© 2023. The Author(s).)

The aim of this study was to compare the sagittal spinal alignment of people with chronic spinal cord injury (SCI) with normal individuals and to determine whether transcutaneous electrical spinal cord stimulation (TSCS) could cause a change in the thoracic kyphosis (TK) and lumbar lordosis (LL) to re-establish normal sagittal spinal alignment. A case series study was conducted, wherein twelve individuals with SCI and ten neurologically intact subjects were scanned using 3D ultrasonography. In addition, three people with SCI having complete tetraplegia participated further to receive a 12-week treatment (TSCS with task-specific rehabilitation) after evaluation of sagittal spinal profile. Pre- and post-assessments were conducted to evaluate the differences in sagittal spinal alignment. The results showed that the TK and LL values for a person with SCI in a dependent seated posture were greater than those of normal subjects for: standing (by TK: 6.8° ± 1.6°; LL: 21.2° ± 1.9°), sitting straight (by TK: 10.0° ± 4.0°; LL: 1.7° ± 2.6°), and relaxed sitting (by TK: 3.9° ± 0.3°; LL: 7.7° ± 1.4°), respectively, indicating an increased risk for spinal deformity. In addition, TK decreased by 10.3° ± 2.3° after the TSCS treatment, showing a reversible change. These results suggest that the TSCS treatment could be used to restore normal sagittal spinal alignment for individuals with chronic SCI.

On social networking sites, people can express themselves in a variety of ways such as creating personalized profiles, commenting on some topics, sharing their experiences and thoughts. Among these technology-enabled features, retweeting other-sourced tweet is a powerful way for users to present themselves. We examine users' retweeting behavior from the perspective of online identity and self-presentation. The empirical results based on a panel dataset crawled from Twitter reveal that, people are prone to retweet topics they are interested in and familiar with, in order to convey a consistent and clear online identity. In addition, we also examine which user groups exhibit a stronger propensity for a clear online identity, considering the practical value of these users to both social media platforms and marketers. By integrating self-presentation theory with social influence theory and social cognitive theory, we propose and confirm that users with higher value in online self-presentation efficacy and users who are more involved with the social media platform have a stronger than average propensity to maintain a consistent online identity, and thus are more likely to retweet familiar topics. These users are characterized by (1) owning a larger number of followers, (2) authoring longer and more original tweets than average, (3) being active in retweeting other-sourced posts. This study contributes to our understanding of SNS users' retweeting behavior and adds to the emerging line of research on online identity. It also provides insights on how microblogging service providers and enterprises can promote people's retweeting behavior., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shi 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.)

Background: Three-dimensional (3D) ultrasonography is nonionizing and has been demonstrated to be a reliable tool for scoliosis assessment, including coronal and sagittal curvatures. It shows a great potential for axial vertebral rotation (AVR) evaluation, yet its validity and reliability need to be further demonstrated., Materials and Methods: Twenty patients with adolescent idiopathic scoliosis (AIS) (coronal Cobb: 26.6 ± 9.1°) received 3D ultrasound scan for twice, 10 were scanned by the same operator, and the other 10 by different operators. EOS Bi-planar x-rays and 3D scan were conducted on another 29 patients on the same day. Two experienced 3D ultrasonographic researchers, with different experiences on AVR measurement, evaluated the 3D ultrasonographic AVR of the 29 patients (55 curves; coronal Cobb angle: 26.9 ± 11.3°). The gold standard AVR was determined from the 3D reconstruction of coronal and sagittal EOS radiographs. Intra-class correlation coefficients (ICCs), mean absolute difference (MAD), standard error measurements (SEM), and Bland-Altman's bias were reported to evaluate the intra-operator and inter-operator/rater reliabilities of 3D ultrasonography. The reliability of 3D ultrasonographic AVR measurements was further validated using inter-method with that of EOS., Results: ICCs for intra-operator and inter-operator/rater reliability assessment were all greater than 0.95. MAD, SEM, and bias for the 3D ultrasonographic AVRs were no more than 2.2°, 2.0°, and 0.5°, respectively. AVRs between both modalities were strongly correlated ( R 2  = 0.901) and not significantly different ( p  = 0.205). Bland-Altman plot also shows that the bias was less than 1°, with no proportional bias between the difference and mean of expected and radiographic Cobb angles., Conclusion: This study demonstrates that 3D ultrasonography is valid and reliable to evaluate AVR in AIS patients. 3D ultrasonography can be a potential tool for screening and following up subjects with AIS and evaluating the effectiveness of nonsurgical treatments., Competing Interests: Y.P. Zheng reports his role as a consultant to Telefield Medical Imaging Limited for the development of Scolioscan, outside the submitted work and he is the inventor of a number of patents related to 3D ultrasound imaging for scoliosis, which has been licensed to Telefield Medical Imaging Limited through Hong Kong Polytechnic University. He is also a director and shareholder of this startup company. All the other author(s) have no conflicts of interest relevant to this article., (© 2023 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Some strains of the dinoflagellate species Prorocentrum hoffmannianum show contrasting ability to produce diarrhetic shellfish poisoning (DSP) toxins. We previously compared the okadaic acid (OA) production level between a highly toxic strain (CCMP2804) and a non-toxic strain (CCMP683) of P. hoffmannianum and revealed that the cellular concentration of OA in CCMP2804 would increase significantly under the depletion of phosphate. To understand the molecular mechanisms, here, we compared and analyzed the proteome changes of both strains growing under normal condition and at phosphate depletion using two-dimensional gel electrophoresis (2-DE). There were 41 and 33 differential protein spots observed under normal condition and phosphate depletion, respectively, of which most were upregulated in CCMP2804 and 22 were common to both conditions. Due to the lack of matched peptide mass fingerprints in the database, de novo peptide sequencing was applied to identify the differentially expressed proteins. Of those upregulated spots in CCMP2804, nearly 60% were identified as peridinin-chlorophyll a-binding protein (PCP), an important light-harvesting protein for photosynthesis in dinoflagellates. We postulated that the high expression of PCP encourages the production of DSP toxins by enhancing the yields of raw materials such as acetate, glycolate and glycine. Other possible mechanisms of toxicity related to PCP might be through triggering the transcription of non-ribosomal peptide synthetase/polyketide synthase genes and the transportation of dinophysistoxin-4 from chloroplast to vacuoles.

The public sector is becoming increasingly appealing. In the context of declining public money to support health studies and public health interventions, public-private partnerships with entities (including government agencies and scientific research institutes) are becoming increasingly important. When forming this type of cooperation, the participants highlight synergies between the private partners and the public's missions or goals. The tasks of private and public sector actors, on the other hand, frequently diverge significantly. The integrity and honesty of public officials, institutions, trust, and faith in those individuals and institutions may all be jeopardized by these collaborations. In this study, we use the institutional corruption framework to highlight systemic concerns raised by PPPs affiliated with the governments of one of South Asia's countries. Overall analytical frameworks for such collaborations tend to downplay or disregard these systemic impacts and their ethical implications, as we argue. We offer some guidelines for public sector stakeholders that want to think about PPPs in a more systemic and analytical way. Partnership as a default paradigm for engagement with the private sector needs to be reconsidered by public sector participants. They also need to be more vocal about which goals they can and cannot fulfill, given the limitations of public financing resources.

Serine incorporator 5 (Ser5), a transmembrane protein, has recently been identified as a host antiviral factor against human immunodeficiency virus (HIV)-1 and gammaretroviruses like murine leukemia viruses (MLVs). It is counteracted by HIV-1 Nef and MLV glycogag. We have investigated whether it has antiviral activity against influenza A virus (IAV), as well as retroviruses. Here, we demonstrated that Ser5 inhibited HIV-1-based pseudovirions bearing IAV hemagglutinin (HA); as expected, the Ser5 effect on this glycoprotein was antagonized by HIV-1 Nef protein. We found that Ser5 inhibited the virus-cell and cell-cell fusion of IAV, apparently by interacting with HA proteins. Most importantly, overexpressed and endogenous Ser5 inhibited infection by authentic IAV. Single-molecular fluorescent resonance energy transfer (smFRET) analysis further revealed that Ser5 both destabilized the pre-fusion conformation of IAV HA and inhibited the coiled-coil formation during membrane fusion. Ser5 is expressed in cultured small airway epithelial cells, as well as in immortal human cell lines. In summary, Ser5 is a host antiviral factor against IAV which acts by blocking HA-induced membrane fusion. IMPORTANCE SERINC5 (Ser5) is a cellular protein which has been found to interfere with the infectivity of HIV-1 and a number of other retroviruses. Virus particles produced in the presence of Ser5 are impaired in their ability to enter new host cells, but the mechanism of Ser5 action is not well understood. We now report that Ser5 also inhibits infectivity of Influenza A virus (IAV) and that it interferes with the conformational changes in IAV hemagglutinin protein involved in membrane fusion and virus entry. These findings indicate that the antiviral function of Ser5 extends to other viruses as well as retroviruses, and also provide some information on the molecular mechanism of its antiviral activity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with an increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that exposure to rapalogs increased susceptibility to SARS-CoV-2 infection in tissue culture and in immunologically naive rodents by antagonizing the cell-intrinsic immune response. We identified 1 rapalog (ridaforolimus) that was less potent in this regard and demonstrated that rapalogs promote spike-mediated entry into cells, by triggering the degradation of the antiviral proteins IFITM2 and IFITM3 via an endolysosomal remodeling program called microautophagy. Rapalogs that increased virus entry inhibited mTOR-mediated phosphorylation of the transcription factor TFEB, which facilitated its nuclear translocation and triggered microautophagy. In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.

Aims: Plasma cell neoplasms (PCNs) may involve the gastrointestinal (GI) tract in two forms: plasmacytoma (PC), an isolated lesion that lacks marrow involvement, and extramedullary myeloma (EMM). However, previous literature on PCNs involving the GI tract, liver, and pancreas is limited. We evaluated the clinicopathologic features of the largest series of GI PCNs to date., Methods and Results: Six institutional archives were searched for GI, liver, and pancreas cases involved with PCNs. Medical records were reviewed for clinical and imaging features. Histopathologic features evaluated included involved organ, tumor grade, and marrow involvement. Overall, 116 cases from 102 patients were identified. The tumors most presented as incidental findings (29%). The liver was most involved (47%), and masses/polyps (29%) or ulcers (21%) were the most common findings. Most cases had high-grade morphology (55%). The majority (74%) of GI PCNs were classified as EMM due to the presence of marrow involvement at some point during the disease course, occurring within a year of marrow diagnosis in 46% of patients. PC was classified in 26% of patients due to the lack of marrow involvement. Most (70%) patients died from disease within 10 years (median 14.1) of diagnosis and more than half (58%) died within 6 months., Conclusion: PC and EMM involving the GI tract, liver, and pancreas have a wide range of clinicopathologic presentations. Tumors may occur virtually anywhere in the GI tract or abdomen and may precede the diagnosis of marrow involvement. Both GI PC and EMM are associated with a poor prognosis., (© 2022 John Wiley & Sons Ltd.)

This study examines the dynamic causality between the carbon emission market and the clean energy market, using an information flow-based, quantitative Liang causality analysis which is firmly grounded on physics and derived from first principles. The dynamic causal relationships between European Union Allowance (EUA) prices and clean energy index allow us to explore whether the causality in return or in variance from CO 2 emission allowances to the clean energy index is time-varying. The results show that the causal relationships in return and in variance between EUA and Clean Energy Index (CEI) are drastically time-varying. For the causality in return, a significant unidirectional long-term and stable causality from CEI to EUA is identified after March 2020. For that in variance, a bidirectional causality is found after March 2020, but values after 2020 are opposite to those in return. It seems when fluctuations in the clean energy market are low, the clean energy market has a weak causal effect on the carbon emission market but when volatility in the clean energy market is increasing, causalities between the two markets are significantly strengthened. These results obtained through this rigorous causality analysis can serve as a reference for academics, market participants, and policymakers to understand the underlying links between EUA prices and clean energy index., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims and Methods: Accurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies., Results: Targeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R 2 =0.42-0.72); inverse relationships were detected with cell junction targets (R 2 =0.49-0.71) and β-catenin (R 2 =0.51-0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively., Conclusions: Pathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach., Competing Interests: Competing interests: AMG, BLA, DCG, JS and RJB declare they were employees of Eli Lilly and Company during this work. MDW, SH, RDM and DCL are employees of Protypia. JB, KKL and EDH have no relevant financial competing interests to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The mobile emergency system is a new emergency mode that provides a solution to deal with increasingly frequent sudden disasters by reasonably allocating mobile emergency facilities and optimizing the allocation of mobile emergency materials. We consider mobile emergency cost and mobile emergency time as two objective functions. This paper establishes a multi-objective mobile emergency material allocation model, and transforms the multi-objective. We choose the emergency material transportation path for coding, and apply the hybrid leapfrog algorithm for material allocation to obtain the optimal solution. Finally, the feasibility of the model is verified by taking Zhengzhou urban area under the "21.7" severe rainstorm and flood disaster in Henan Province. The result analyses show that the model can correspond to each stage of mobile emergency material allocation based on the value of cost preference, and put forward suggestions on the location of mobile emergency facilities and the amount of material allocation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Fu, Lai and Ram.)

Purpose: Using X-ray to evaluate adolescent idiopathic scoliosis (AIS) conditions is the clinical gold standard, with potential radiation hazards. 3D ultrasound has demonstrated its validity and reliability of estimating X-ray Cobb angle (XCA) using spinous process angle (SPA), which can be automatically measured. While angle measurement with ultrasound using spine transverse process-related landmarks (UCA) shows better agreed with XCA, its automatic measurement is challenging and not available yet. This research aimed to analyze and measure scoliotic angles through a novel semi-automatic UCA method., Methods: 100 AIS subjects (age: 15.0 ± 1.9 years, gender: 19 M and 81 F, Cobb: 25.5 ± 9.6°) underwent both 3D ultrasound and X-ray scanning on the same day. Scoliotic angles with XCA and UCA methods were measured manually; and transverse process-related features were identified/drawn for the semi-automatic UCA method. The semi-automatic method measured the spinal curvature with pairs of thoracic transverse processes and lumbar lumps in respective regions., Results: The new semi-automatic UCA method showed excellent correlations with manual XCA (R 2  = 0.815: thoracic angles R 2  = 0.857, lumbar angles R 2  = 0.787); and excellent correlations with manual UCA (R 2  = 0.866: thoracic angles R 2  = 0.921, lumbar angles R 2  = 0.780). The Bland-Altman plot also showed a good agreement against manual UCA/XCA. The MADs of semi-automatic UCA against XCA were less than 5°, which is clinically insignificant., Conclusion: The semi-automatic UCA method had demonstrated the possibilities of estimating manual XCA and UCA. Further advancement in image processing to detect the vertebral landmarks in ultrasound images could help building a fully automated measurement method., Level of Evidence: Level III., (© 2021. The Author(s), under exclusive licence to Scoliosis Research Society.)

This paper develops an integrated framework to forecast the volatility of crude oil prices by considering the impacts of extreme events (structural breaks). The impacts of extreme events are vital to improving prediction accuracy. Aiming to demonstrate the crude oil price fluctuation and the impacts of external events, this paper employs the complementary ensemble empirical mode decomposition (CEEMD). It decomposes the crude oil price into some constituents at various frequencies to extract a market fluctuation, a shock from extreme events and a long-term trend. The shock from extreme events is found to be the most crucial element in deciding the crude oil prices. Then we combine the iterative cumulative sum of squares (ICSS) test with the Chow test to get the structural breaks and analyze the extreme event impacts. Finally, this paper combines the structural breaks, the autoregressive integrated moving average (ARIMA) model, and the support vector machine (SVM) to make a forecast of the crude oil prices. The empirical process proves that the CEEMD-ARIMA-SVM model with structural breaks performs the best when compared with the other ARIMA-type models and SVM-type models. The framework offers an insightful view to help decision-makers and can be used in many areas., Supplementary Information: The online version contains supplementary material available at 10.1007/s00500-022-07276-5., Competing Interests: Conflict of interestNo potential conflict of interest was reported by the author(s)., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Background: Collagen production by activated hepatic stellate cells (HSCs) to encapsulate injury is part of the natural wound-healing response in injured liver. However, persistent activation of HSCs can lead to pathological fibrogenesis. Such persistent HSC activation could be mediated by norepinephrine (NE), a reaction product of dopamine beta-hydroxylase (DBH)., Objective: To investigate the potential paracrine role of NE in hepatotoxin thioacetamide (TAA)-induced liver fibrosis., Methods: In TAA-treated mice, fibrotic liver tissue showed significant increases in the mRNA expression of DBH up to 14-fold and collagen up to 7-fold. Immunohistochemical staining showed increased DBH protein expression in fibrotic liver tissue. Parenchymal hepatocyte cell line HepG2 expressed DBH and secreted NE, and the conditioned medium of HepG2 cells promoted collagenesis in nonparenchymal HSC cell line LX-2. TAA treatment increased DBH expression by 170% in HepG2 cells, as well as increased NE by 120% in the conditioned medium of HepG2 cells. The conditioned medium of TAA-treated HepG2 cells was used to culture LX-2 cells, and was found to increase collagen expression by 80% in LX-2 cells. Collagen expression was reduced by pre-treating HepG2 cells with siRNA targeting DBH or by adding NE antagonists to the conditioned medium., Results: Finally, TAA-induced oxidative stress in HepG2 cells was associated with induction of DBH expression. Collectively, our results suggest a potential role for DBH/NE-mediated crosstalk between hepatocytes and HSCs in fibrogenesis., Conclusion: From a therapeutic standpoint, antagonism of DBH/NE induction in hepatocytes might be a useful strategy to suppress pathological fibrogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This paper proposes a multiple criteria group decision making with individual preferences (MCGDM-IP) to address the robot selection problem (RSP). Four objective criteria elicitation approaches, namely, Shannon entropy approach, CRITIC approach, distance-based approach, and ideal-point approach, are proposed to indicate individual decision makers. A preliminary group decision matrix is therefore formulated. Both preferential differences representing the preference degrees among different robots, and preferential priorities representing the favorite ranking of robots for each individual decision maker, are analyzed to propose a revised group decision matrix. A satisfaction index is developed to manifest the merits of the proposed MCGDM-IP. An illustrative example using the data drawn from previous literature is conducted to indicate the effectiveness and validity of MCGDM-IP. The results demonstrate that the MCGDM-IP could generate a more satisfactory scheme to evaluate and select industrial robots, with an improvement of group satisfactory level as 2.12%., Competing Interests: The authors have declared that no competing interests exist.

Karenia mikimotoi is a well-known harmful algal bloom species. Blooms of this dinoflagellate have become a serious threat to marine life, including fish, shellfish, and zooplanktons and are usually associated with massive fish death. Despite the discovery of several toxins such as gymnocins and gymnodimines in K. mikimotoi , the mechanisms underlying the ichthyotoxicity of this species remain unclear, and molecular studies on this topic have never been reported. The present study investigates the fish-killing mechanisms of K. mikimotoi through comparative proteomic analysis. Marine medaka, a model fish organism, was exposed to K. mikimotoi for a three-part time period (LT 25 , LT 50 and LT 90 ). Proteins extracted from the whole fish were separated by using two-dimensional gel electrophoresis, and differentially expressed proteins were identified with reference to an untreated control. The change in fish proteomes over the time-course of exposure were analyzed. A total of 35 differential protein spots covering 19 different proteins were identified, of which most began to show significant change in expression levels at the earliest stage of intoxication. Among the 19 identified proteins, some are closely related to the oxidative stress responses, energy metabolism, and muscle contraction. We propose that oxidative stress-mediated muscle damage might explain the symptoms developed during the ichthyotoxicity test, such as gasping for breath, loss of balance, and body twitching. Our findings lay the foundations for more in-depth studies of the mechanisms of K. mikimotoi 's ichthyotoxicity.

This research gave an overview of coordinated hospital planning issues. In these issues, patients desire an arrangement for different source types, ideally as quickly as time permits. This field of context has just picked up academic interest, despite its reality since 1995. The way may discover a clarification for the above aspect that managing the hospital sources is regularly performed separately without taking a bigger picture. Therefore, it is particularly valid if the sources are situated in different departments. Another subsequent clarification may be related to the notoriety of the patient flow context. Hence, patients shouldn't be planned in these issues to be queued for another source or leave the system in case of their satisfaction of solicitation for the services at a particular source. The primary contribution of the present research is assisting present and new scholars via enumeration for every progression of the study of accessible decisions in the present context. Such means could be represented by major references for scientists to discover such studies endeavors tailored to their respective requirements. This principle removes the message: scientists ought to consistently coordinate their decisions concerning the setting, the capacity, and the approaches, as not all blends are conceivable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XW declared a shared affiliation, with no collaboration, with the authors to the handling editor at the time of the review., (Copyright © 2021 Heydari, Lai and Xiaohu.)