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Abstract Background To present a case of conjunctival growth on the amniotic membrane and subsequent pathology revealing conjunctival squamous metaplasia in a patient with Stevens-Johnson syndrome. Case presentation A 21-year-old female presented with painful, blurred vision in both eyes for two weeks. She was diagnosed with Stevens-Johnson syndrome 5 weeks before. Due to bilateral corneal epithelial defects, ProKera®, an amniotic membrane corneal bandage with a polycarbonate ring, was placed in both eyes. However, three weeks later, a slit-lamp examination revealed vascularized tissue growth from the palpebral conjunctiva to the amniotic membrane, along with symblepharon formation in the left eye. The patient underwent conjunctival biopsy, amniotic membrane removal, and symblepharon release. Pathology report showed the growth of squamous epithelium on the acellular amniotic membrane. Immunohistochemistry further supported the diagnosis, revealing squamous markers through p40 staining and highlighting the presence of the amniotic membrane using trichrome stain. Three months later, the patient’s visual acuity had improved to 20/25 and no symblepharon was noted. Conclusions This is the first case of conjunctival squamous metaplasia on amniotic membrane associated with Stevens-Johnson syndrome. Our case indicates that, despite the anti-inflammatory properties of amniotic membrane, conjunctival squamous metaplasia may arise after amniotic membrane grafting due to intense inflammation in Stevens-Johnson syndrome. Clinicians should conduct regular monitoring before amniotic membrane dissolution to preclude the development of conjunctival squamous metaplasia on the membrane and potential invasion into the cornea.

Abstract Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

Abstract There is an urgent need for models that can robustly detect past and project future ecosystem changes and risks to the services that they provide to people. The Fisheries and Marine Ecosystem Model Intercomparison Project (FishMIP) was established to develop model ensembles for projecting long‐term impacts of climate change on fisheries and marine ecosystems while informing policy at spatio‐temporal scales relevant to the Inter‐Sectoral Impact Model Intercomparison Project (ISIMIP) framework. While contributing FishMIP models have improved over time, large uncertainties in projections remain, particularly in coastal and shelf seas where most of the world's fisheries occur. Furthermore, previous FishMIP climate impact projections have been limited by a lack of global standardized historical fishing data, low resolution of coastal processes, and uneven capabilities across the FishMIP community to dynamically model fisheries. These features are needed to evaluate how reliably the FishMIP ensemble captures past ecosystem states ‐ a crucial step for building confidence in future projections. To address these issues, we have developed FishMIP 2.0 comprising a two‐track framework for: (a) Model evaluation and attribution of past changes and (b) future climate and socioeconomic scenario projections. Key advances include improved historical climate forcing, which captures oceanographic features not previously resolved, and standardized global fishing forcing to test fishing effects systematically across models. FishMIP 2.0 is a crucial step toward a detection and attribution framework for changing marine ecosystems and toward enhanced policy relevance through increased confidence in future ensemble projections. Our results will help elucidate pathways toward achieving sustainable development goals.

This study investigates the historical changes in resource development of offshore and coastal fisheries around Taiwan from 1970 to 2021 using the mean trophic level (MTL) and Fishing-in-Balance (FiB) indices. Utilizing data from the Fisheries Statistical Yearbook, three scenarios were employed to assess the effects of highly migratory, oceanic migratory, and seasonal migratory fish species on the MTL and FiB indices. The analysis revealed a continuous increase in MTL for offshore and coastal fisheries, suggesting shifts in the trophic structure and potential over-exploitation of higher trophic level species. The FiB index for offshore fisheries exhibited a declining pattern after 1990, reflecting the depletion of indigenous fish stocks, while the FiB for coastal fisheries showed an increasing trend from 1970 until the 2000s, followed by a decrease, highlighting unsustainable fishing practices. Moreover, the study identified Scomber australasicus, targeted by Taiwanese Purse Seine, as an influential species affecting the resource dynamics of offshore fisheries. The trawling fisheries would also be a crucial issue affecting the indigenous resource dynamics of offshore fisheries in Taiwan. This study identified a fishing-down mechanism within indigenous fishery dynamics. The potential over-exploitation of fish stocks could result in long-term unsustainable practices if left unaddressed. This study advocates for enhanced fisheries management through stricter regulations on fishing gear, continuous monitoring, and adaptive management strategies. These measures are essential for achieving sustainable development goals and conserving marine biodiversity in Taiwan’s waters. By addressing these critical issues, Taiwan can better manage its fisheries resources and promote ecological balance.

Abstract Background Extreme precipitation events often cause sudden drops in salinity, leading to disease outbreaks in shrimp aquaculture. Evidence suggests that environmental stress increases animal host susceptibility to pathogens. However, the mechanisms of how low salinity stress induces disease susceptibility remain poorly understood. Methods We investigated the acute response of shrimp gut microbiota exposed to pathogens under low salinity stress. For comparison, shrimp were exposed to Vibrio infection under two salinity conditions: optimal salinity (Control group) and low salinity stress (Stress group). High throughput 16S rRNA sequencing and real-time PCR were employed to characterize the shrimp gut microbiota and quantify the severity level of Vibrio infection. Results The results showed that low salinity stress increased Vibrio infection levels, reduced gut microbiota species richness, and perturbed microbial functions in the shrimp gut, leading to significant changes in lipopolysaccharide biosynthesis that promoted the growth of pathogens. Gut microbiota of the bacterial genera Candidatus Bacilliplasma, Cellvibrio, and Photobacterium were identified as biomarkers of the Stress group. The functions of the gut microbiota in the Stress group were primarily associated with cellular processes and the metabolism of lipid-related compounds. Conclusions Our findings reveal how environmental stress, particularly low salinity, increases shrimp susceptibility to Vibrio infection by affecting the gut microbiota. This highlights the importance of avoiding low salinity stress and promoting gut microbiota resilience to maintain the health of shrimp.

Abstract Objective Our objective was to create a machine learning architecture capable of identifying obstructive sleep apnea (OSA) patterns in single-lead electrocardiography (ECG) signals, exhibiting exceptional performance when utilized in clinical data sets. Methods We conducted our research using a data set consisting of 1656 patients, representing a diverse demographic, from the sleep center of China Medical University Hospital. To detect apnea ECG segments and extract apnea features, we utilized the EfficientNet and some of its layers, respectively. Furthermore, we compared various training and data preprocessing techniques to enhance the model’s prediction, such as setting class and sample weights or employing overlapping and regular slicing. Finally, we tested our approach against other literature on the Apnea-ECG database. Results Our research found that the EfficientNet model achieved the best apnea segment detection using overlapping slicing and sample-weight settings, with an AUC of 0.917 and an accuracy of 0.855. For patient screening with AHI > 30, we combined the trained model with XGBoost, leading to an AUC of 0.975 and an accuracy of 0.928. Additional tests using PhysioNet data showed that our model is comparable in performance to existing models regarding its ability to screen OSA levels. Conclusions Our suggested architecture, coupled with training and preprocessing techniques, showed admirable performance with a diverse demographic dataset, bringing us closer to practical implementation in OSA diagnosis. Trial registration The data for this study were collected retrospectively from the China Medical University Hospital in Taiwan with approval from the institutional review board CMUH109-REC3-018.

Study region: The southwestern coast of Taiwan. Study focus: By employing sea-level rise (SLR) projections from the Sixth Assessment Report, we assess the future high tide flooding (HTF) and the resulting inundation extents and evaluate the impacts on populations and economic losses. New hydrological insights for the region: Under the low-emissions scenario, SLR-induced minor HTF days, i.e., 0.55 m above the mean higher high water (MHHW) are projected to exceed 300 annually by 2100; moderate HTF (0.85 m above the MHHW) events are expected to occur daily in the high-emissions scenario by 2090; major HTF (1.2 m above the MHHW) events were projected to occur in 2070, regardless of the emission scenario considered; regarding the extent of inundation, the projected HTF events would lead to a flooded area ranging from 30 to 600 km2. The impact on the present population ranged from 41,000 to 490,000 individuals. The upper limit of total economic losses based on current land use resulting from HTF was anticipated to range from 3.25 million US dollars to 35.31 million US dollars across the low-, medium-, and high-emission scenarios. The at-risk population decreased from 520,000 in 2008–490,000 in 2022, representing a decline of 5.8 % over 15 years in this coastal region.

Abstract Automated coronary angiography assessment requires precise vessel segmentation, a task complicated by uneven contrast filling and background noise. Our research introduces an ensemble U-Net model, SE-RegUNet, designed to accurately segment coronary vessels using 100 labeled angiographies from angiographic images. SE-RegUNet incorporates RegNet encoders and squeeze-and-excitation blocks to enhance feature extraction. A dual-phase image preprocessing strategy further improves the model's performance, employing unsharp masking and contrast-limited adaptive histogram equalization. Following fivefold cross-validation and Ranger21 optimization, the SE-RegUNet 4GF model emerged as the most effective, evidenced by performance metrics such as a Dice score of 0.72 and an accuracy of 0.97. Its potential for real-world application is highlighted by its ability to process images at 41.6 frames per second. External validation on the DCA1 dataset demonstrated the model's consistent robustness, achieving a Dice score of 0.76 and an accuracy of 0.97. The SE-RegUNet 4GF model's precision in segmenting blood vessels in coronary angiographies showcases its remarkable efficiency and accuracy. However, further development and clinical testing are necessary before it can be routinely implemented in medical practice.

In this paper, we consider of the following second-order Hamiltonian system \begin{equation*} \ddot{u}(t)-L(t)u(t)+\nabla W(t,u(t))=0,\qquad \forall t \in \mathbb{R}, \end{equation*} where $W(t,x)$ is subquadratic at infinity. With a competition condition, we establish the existence of homoclinic solutions by using the variational methods. In our theorem, the smallest eigenvalue function $l(t)$ of $L(t)$ is not necessarily coercive or bounded from above and $W(t,x)$ is not necessarily integrable on $\mathbb{R}$ with respect to $t$. Our theorem generalizes many known results in the references.

In medical and healthcare application scenarios, data integrity and user privacy are often concerned the most. A sanitizable signature scheme is a common adopted approach since it admits an authorized person to sanitize partial sensitive information of signed messages while keeping the correctness of preserved message and signature pairs. A certificateless sanitizable signature scheme further enjoys the merits of certificateless public key systems. That is, it is unnecessary to maintain the public key certificates in traditional cryptosystems or deal with the key escrow problem in identity-based systems. However, the functionality of batch verification for retained message-signature pairs and the revocation mechanism are still lack in previous works. To resolve these issues, the authors propose a revocable certificateless sanitizable signature scheme with batch verification in this paper. The revocation mechanism is fulfilled by combining user’s private key with an updatable time key. Hence, a revoked user is unable to request the renewed time key. We also provide a formal proof that our proposed system satisfies the security requirement of existential unforgeability under adaptive chosen-message attacks (EUF-CMA) in the random oracle model. In comparison to related variants, our system demonstrates superior functionality and computational efficiency.

Understanding the feeding behavior of Portunidae crabs with different baits can improve bait selection and is crucial for improving the effectiveness of crab fishing gear. This study, conducted in indoor experimental tanks, used trajectory tracking software and two types of natural baits (mackerel (Scomber australasicus) and squid (Uroteuthis chinensis)) to understand the behavior of Portunus sanguinolentus and Charybdis natator. Spatial distribution results showed that P. sanguinolentus was frequently present in the starting area (S1) and bait area (S3) in the control and treatment groups. However, C. natator was frequently present and concentrated in the S1 area compared to the middle areas S2 and S3, and only in the mackerel treatments were they observed to move to the S3 areas. The spatial distribution results indicate that P. sanguinolentus shows a stronger willingness to explore its surroundings, while C. natator is generally in a stationary, wait-and-see state. The swimming speeds of P. sanguinolentus and C. natator showed different trends. P. sanguinolentus showed continuous movement with no fixed speed when no bait was present in the control groups. However, when treated with mackerel and squid, the average swimming speed of P. sanguinolentus was faster (>5 cm/s) in the first 10 min and showed a more stable movement speed when searching for the baits. C. natator showed a stationary or low movement speed when no bait was present in the control groups. However, when C. natator perceived the presence of the baits in the treatment groups, their movement speed increased in the first 10 min. In addition, there was no significant difference between male and female crabs of P. sanguinolentus and C. natator in movement speed in the control and treatment groups. Compared to C. natator, P. sanguinolentus might be more sensitive to natural baits, as shown by its movement from S1 to S3. The results indicate that the species of Portunidae crabs show different bait selections. Natural baits (mackerel and squid) are recommended for catching P. sanguinolentus in crab fisheries.

Vortex-induced vibration is a type of wind-induced vibration occurring frequently in large-span sea-crossing bridges under relatively low wind speeds, posing a threat to the structural fatigue performance and driving comfort. Identifying the instantaneous occurrence moments of vortex-induced vibration is a prerequisite for establishing a data-driven prediction model for vortex-induced vibration, and it is of great significance for the monitoring and early warning of vortex-induced vibration performance in bridges. To automatically detect the occurrence moments of vortex-induced vibration and establish a correlation model between vortex-induced vibration amplitude and environmental factors, this study proposes a fuzzy C-means clustering-based classification method. In order to detect the occurrence moments of vortex-induced vibration more finely, only short-term or even instantaneous structural vibration indicators were selected and transformed for distribution as clustering features. The entire detection process could be carried out unsupervised, reducing the manual cost of obtaining vortex-induced vibration information from massive monitoring data. Finally, actual vortex-induced vibration test data from a certain overseas bridge was utilized to verify the feasibility of this method. Based on the classification results, the correlation between vortex-induced vibration amplitude and environmental variables was determined, providing valuable guidance for predicting vortex-induced vibration amplitudes.

Abstract Large-artery atherosclerosis (LAA) is a leading cause of cerebrovascular disease. However, LAA diagnosis is costly and needs professional identification. Many metabolites have been identified as biomarkers of specific traits. However, there are inconsistent findings regarding suitable biomarkers for the prediction of LAA. In this study, we propose a new method integrates multiple machine learning algorithms and feature selection method to handle multidimensional data. Among the six machine learning models, logistic regression (LR) model exhibited the best prediction performance. The value of area under the receiver operating characteristic curve (AUC) was 0.92 when 62 features were incorporated in the external validation set for the LR model. In this model, LAA could be well predicted by clinical risk factors including body mass index, smoking, and medications for controlling diabetes, hypertension, and hyperlipidemia as well as metabolites involved in aminoacyl-tRNA biosynthesis and lipid metabolism. In addition, we found that 27 features were present among the five adopted models that could provide good results. If these 27 features were used in the LR model, an AUC value of 0.93 could be achieved. Our study has demonstrated the effectiveness of combining machine learning algorithms with recursive feature elimination and cross-validation methods for biomarker identification. Moreover, we have shown that using shared features can yield more reliable correlations than either model, which can be valuable for future identification of LAA.

Abstract Objective This study evaluated the association between serum albumin levels and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. Methods Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between albumin levels and preoperative DVT. Analyses were performed using EmpowerStats and the R software. Results A total of 1819 patients were included in this study. The average age was 79.37 ± 6.88 years. There were 550 males and 1269 females. The preoperative albumin was 38.19 ± 4.07 g/L. There were 580 (31.89%) preoperative DVTs. Multivariate binary logistic regression showed that albumin level was associated with preoperative DVT (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.91–0.97, P = 0.0002) after adjusting for confounding factors. The fully adjusted model showed a DVT risk decrease of 6% when albumin concentration increased by one g/L after controlling for confounding factors. In addition, the trend test and propensity score matching also showed a stable linear correlation between albumin level and preoperative DVT. Conclusion Serum albumin is associated with preoperative DVT in geriatric patients with hip fractures, and it could be considered a predictor for the risk of DVT. Registration ID ChiCTR2200057323.

In this paper, we obtain the multiplicity of homoclinic solutions for a class of asymptotically autonomous Hamiltonian systems with indefinite sign potentials. The concentration-compactness principle is applied to show the compactness. As a byproduct, we obtain the uniqueness of the positive ground state solution for a class of autonomous Hamiltonian systems and the best constant for Sobolev inequality which are of independent interests.

This study detailed the course design principles and implementation of project-based learning (PBL) in a technology-themed graduate-level online course. Students were trained to develop knowledge and skills in instructional leadership, such as the capability to design, deliver, and evaluate educational technology professional development programs. Pre- and post- survey data were collected to examine any change in students' knowledge and skills in instructional leadership by completing this course (N = 18). Quantitative findings revealed positive learning outcomes, and there was statistical significance regarding student improvement in knowledge and skills of instructional leadership, rendering the PBL approach viable.

Research on Digital Game-Based learning (DGBL) indicated it is effective in inducing student motivation and learning outcomes. Teachers as gatekeepers of technology should maneuver DGBL as pedagogical approach to engage students. In this convergent mixed method study, the researcher surveyed 116 pre-service, internship, and in-service teachers about their attitudes, self-efficacy, teaching philosophy, and perceived barriers toward the implementation of DGBL. Qualitative and quantitative data were collected and corroborated. Results showed majority of teachers gravitated toward Edutainment Games and Educational Applications based on pre-existing familiarity, comfortableness, and ease of use. Findings revealed misalignment between teachers’ endorsed teaching philosophy and their preferred game genre for use in instruction. The implication is that teachers during internship and post-induction should become educated in digital games and corresponding learning theory inherent in its design, so they can leverage teaching philosophy, knowledge and strategies to instruct in tandem with a pedagogically sound and thoughtfully chosen game.

Abstract Background The Bacillus cereus Sigma B (SigB) dependent general stress response is activated via the two-component RsbKY system, which involves a phosphate transfer from RsbK to RsbY. It has been hypothesized that the Hpr-like phosphocarrier protein (Bc1009) encoded by bc1009 in the SigB gene cluster may play a role in this transfer, thereby acting as a regulator of SigB activation. Alternatively, Bc1009 may be involved in the activation of a subset of SigB regulon members. Results We first investigated the potential role of bc1009 to act as a SigB regulator but ruled out this possibility as the deletion of bc1009 did not affect the expression of sigB and other SigB gene cluster members. The SigB-dependent functions of Bc1009 were further examined in B. cereus ATCC14579 via comparative proteome profiling (backed up by transcriptomics) of wt, Δbc1009 and ΔsigB deletion mutants under heat stress at 42 °C. This revealed 284 proteins displaying SigB-dependent alterations in protein expression levels in heat-stressed cells, including a subgroup of 138 proteins for which alterations were also Bc1009-dependent. Next to proteins with roles in stress defense, newly identified SigB and Bc1009-dependent proteins have roles in cell motility, signal transduction, transcription, cell wall biogenesis, and amino acid transport and metabolism. Analysis of lethal stress survival at 50 °C after pre-adaptation at 42 °C showed intermediate survival efficacy of Δbc1009 cells, highest survival of wt, and lowest survival of ΔsigB cells, respectively. Additional comparative proteome analysis of non-stressed wt and mutant cells at 30 °C revealed 96 proteins with SigB and Bc1009-dependent differences in levels: 51 were also identified under heat stress, and 45 showed significant differential expression at 30 °C. This includes proteins with roles in carbohydrate/ion transport and metabolism. Overlapping functions at 30 °C and 42 °C included proteins involved in motility, and ΔsigB and Δbc1009 cells showed reduced motility compared to wt cells in swimming assays at both temperatures. Conclusion Our results extend the B. cereus SigB regulon to > 300 members, with a novel role of SigB-dependent Bc1009 in the activation of a subregulon of > 180 members, conceivably via interactions with other transcriptional regulatory networks.

Abstract Astaxanthin (AST), a super antioxidant with coloring and medical properties, renders it a beneficial feed additive for shrimp. This study conducted a white shrimp feeding trial of 3S, 3’S isoform AST, which was derived from metabolic-engineered Kluyveromyces marxianus fermented broth (TB) and its extract (TE) compared to sources from two chemically synthetic ASTs (Carophyll Pink [CP] and Lucantin Pink [LP]), which contain 3S, 3’S, 3R, 3’S (3S, 3’R) and 3R, 3’R isoforms ratio of 1:2:1. The effects on red coloration, immune parameters and resistance to Vibrio infection were evaluated. Four AST sources were incorporated into the diets at concentrations of 0 (control), 100 mg kg−1 (TB100, TE100, CP100, and LP100), and 200 mg kg−1 (TB200, TE200, CP200, and LP200). Results revealed that in week 4, shrimps that received AST-supplemented feeds, especially TB100, TB200, and TE200, significantly increased redness (a*) values. Immune responses including phagocytosis activity, superoxide-anion production, phenoloxidase activity, and immune-related genes were examined on days 0, 1, 2, 4, 7, 14, 21, and 28. Generally, shrimps that received AST-supplemented feeds exhibited higher immune responses on days 7 and 14 than the control feed. Gene expression levels of superoxide dismutase and glutathione peroxidase were significantly upregulated on days 7 and 14 in shrimps that received AST-supplemented feeds, while genes of penaeidins, antilipopolysaccharide factor, and lysozyme were upregulated on days 4, 7, and 14, especially received TB200 and TE200. Furthermore, shrimps that received TB100, TE100, CP100, and LP100 7 days were then challenged with Vibrio parahaemolyticus and the result demonstrated higher survival rates especially TB100 at 168 h than the control feed. In conclusion, incorporating AST into the diets enhanced shrimp red coloration, immune parameters, and resistance against V. parahaemolyticus infection. The K. marxianus-derived AST exhibited higher performance than did chemical AST to be a potential feed additive in shrimp aquaculture.

Abstract Pancreatic cancer (PC) is a deadly disease, and its post‐transcriptional gene regulation mechanism remains unclear. The abundant extracellular matrix (ECM) in PC plays an important role in tumor progression. This study is the first to focus on the role of N6‐methyladenosine (m6A) RNA methylation, an emerging post‐transcriptional regulatory mechanism, in the regulation of the ECM in PC. Here, we found that ADAMTS2, COL12A1, and THBS2 were associated with the prognosis of PC by comprehensive analysis of differentially expressed genes from two independent GEO expression profile datasets and m6A‐related genes in RMVar database (PAAD). GO and KEGG enrichment analysis found that these m6A‐related targets are chiefly functionally concentrated in the ECM region and participate in ECM signal transduction. Correlation analysis revealed that these genes can be regulated by the demethylase FTO. Cell biology function assays showed that knockdown of FTO‐inhibited PC cell abilities to migrate and invade in vitro. qRT‐PCR and MeRIP experiments showed that after knockdown of FTO, the mRNA levels of ADAMTS2, COL12A1, and THBS2 and their m6A modification levels were significantly reduced. These results indicate that m6A RNA demethylation is associated with the regulation of ECM in PC. In conclusion, m6A RNA demethylase FTO regulates ECM‐related genes and promotes PC cell abilities to migrate and invade, our work provides a new perspective on the molecular mechanism of PC progression.

Alzheimer’s disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer’s disease research; however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer’s disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer’s disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer’s disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer’s disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer’s disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer’s disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed.

Abstract Similarity measures are very effective and meaningful tool used for evaluating the closeness between any two attributes which are very important and valuable to manage awkward and complex information in real-life problems. Therefore, for better handing of fuzzy information in real life, Ullah et al. (Complex Intell Syst 6(1): 15–27, 2020) recently introduced the concept of complex Pythagorean fuzzy set (CPyFS) and also described valuable and dominant measures, called various types of distance measures (DisMs) based on CPyFSs. The theory of CPyFS is the essential modification of Pythagorean fuzzy set to handle awkward and complicated in real-life problems. Keeping the advantages of the CPyFS, in this paper, we first construct an example to illustrate that a DisM proposed by Ullah et al. does not satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Then, combining the 3D Hamming distance with the Hausdorff distance, we propose a new DisM for CPyFSs, which is proved to satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Moreover, similarly to some DisMs for intuitionistic fuzzy sets, we present some other new complex Pythagorean fuzzy DisMs. Finally, we apply our proposed DisMs to a building material recognition problem and a medical diagnosis problem to illustrate the effectiveness of our DisMs. Finally, we aim to compare the proposed work with some existing measures is to enhance the worth of the derived measures.

Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N6-methyladenosine (m6A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m6A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m6A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro, as well as tumour growth in vivo. Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m6A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m6A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.

ABSTRACT Acute hepatopancreatic necrosis disease (AHPND), a high-mortality-rate shrimp disease, is caused by specific Vibrio parahaemolyticus (Vp) strains with a plasmid encoding the PirABVp toxins. As a bacterial pathogen, the invasion of AHPND-causing Vp might impose pressure on commensal microbiota in the shrimp gut, while the relationship between the pathogenesis of AHPND and the dysbiosis of gut bacterial communities remains unclear. Here we explored the temporal changes of shrimp gut microbiota in response to AHPND-causing and non-AHPND-causing Vp strains, with the non-infected controls as a baseline of the shrimp gut microbiota. The diversity and composition of bacterial communities from 168 gut samples (covering three treatments at seven time points with eight individuals per set) were investigated using 16S rRNA gene metabarcoding with high-throughput sequencing. The results showed that (i) species diversity of gut bacterial communities declined in Vp-infected shrimp, independent of the strain pathogenicity; (ii) taxonomic compositions of gut bacterial communities were significantly different between shrimp infected by AHPND-causing and non-AHPND-causing Vp strains; (iii) short-term (within 6 hours) compositional shifts in the gut microbiota were found only in AHPND-causing Vp-infected shrimp; (iv) the gut microbiota of AHPND-causing Vp-infected shrimp was enriched with genera Photobacterium and Vibrio, with a decline in Candidatus Bacilliplasma; and (v) functional predictions suggested the loss of normal metabolism due to compositional shifts in the gut microbiota. Our work reveals distinct features of community dynamics in shrimp gut microbiota, associated with pathogenic versus non-pathogenic Vibrio infections, providing a new perspective of the pathogenesis of AHPND. IMPORTANCE Shrimp production is continually threatened by newly emerging diseases, such as AHPND, which is caused by specific Vp strains. Previous studies on the pathogenesis of AHPND have mainly focused on the histopathology and immune responses of the host. However, more attention needs to be paid to the gut microbiota, which acts as the first barrier to pathogen colonization. In this study, we revealed that shrimp gut microbiota responded differently to pathogenic and non-pathogenic Vp strains, with bacterial genera Photobacterium and Vibrio enriched in pathogenic Vp-infected shrimp, and Candidatus Bacilliplasma enriched in non-pathogenic Vp-infected shrimp. Moreover, functional predictions suggested that changes in taxonomic compositions would further affect normal metabolic functions, emphasizing the importance of sustaining an equilibrium in the gut microbiota. Several biomarkers associated with specific microbial taxa and functional pathways were identified in our data sets, which help predict the incidence of disease outcomes.

Objectives This study aimed to conduct a thorough analysis of fluid retention-associated adverse events (AEs) associated with BCR::ABL inhibitors.Design A retrospective pharmacovigilance study.Setting Food and Drug Administration Adverse Event Reporting System (FAERS) database for BCR::ABL inhibitors was searched from 1 January 2004 to 30 September 2021.Main outcome measures Reporting OR (ROR) and 95% CI were used to detect the signals. ROR was calculated by dividing the odds of fluid retention event reporting for the target drug by the odds of fluid retention event reporting for all other drugs. The signal was considered positive if the lower limit of 95% CI of ROR was >1. The analysis was run only considering coupled fluid retention events/BCR::ABL inhibitors with at least three cases.Results A total of 97 823 reports were identified in FAERS. Imatinib had the most fluid retention signals, followed by dasatinib and nilotinib, while bosutinib and ponatinib had fewer signals. Periorbital oedema (ROR=24.931, 95% CI 22.404 to 27.743), chylothorax (ROR=161.427, 95% CI 125.835 to 207.085), nipple swelling (ROR=48.796, 95% CI 26.270 to 90.636), chylothorax (ROR=35.798, 95% CI 14.791 to 86.642) and gallbladder oedema (ROR=77.996, 95% CI 38.286 to 158.893) were the strongest signals detected for imatinib, dasatinib, nilotinib, bosutinib and ponatinib, respectively. Pleural effusion, pericardial effusion and pulmonary oedema were detected for all BCR::ABL inhibitors, with dasatinib having the highest RORs for pleural effusion (ROR=37.424, 95% CI 35.715 to 39.216), pericardial effusion (ROR=14.146, 95% CI 12.649 to 15.819) and pulmonary oedema (ROR=11.217, 95% CI 10.303 to 12.213). Patients aged ≥65 years using dasatinib, imatinib, nilotinib or bosutinib had higher RORs for pleural effusion, pericardial effusion and pulmonary oedema. Patients aged ≥65 years and females using imatinib had higher RORs for periorbital oedema, generalised oedema and face oedema.Conclusions This pharmacovigilance study serves as a clinical reminder to physicians to be more vigilant for fluid retention-associated AEs with BCR::ABL inhibitors.

Abstract Background Cardiac myxoma is the most common benign cardiac tumor. Its tremendous size and fragile character severely bother the surgeons. Several minimal invasive approaches had been applied for radical tumor excision. The wound was forcibly enlarged for en-bloc specimen removal and prevention of debris sputtering. Case presentation We reported a case of huge tricuspid valve (TV) myxoma managed by robot-assisted endoscopic tumor resection and TV repair, with initial presentation of worsening shortness of breath for two months. The tumor was downsized with a morcellator and removed through a keyhole wound (1.1 cm in diameter). The patient recovered uneventfully and was discharged after four days. Conclusions With the first morcellator application, this might be the smallest surgical wound reported after the removal of a huge cardiac myxoma. The ICU and hospital stays were shortened. This might be effectively applied to further minimally invasive surgeries for cardiac tumor excision.

Abstract Spatial variations in tuna population and abundance are strongly linked to large-scale climate fluctuations, such as the Pacific decadal oscillation (PDO) and Atlantic multidecadal oscillation (AMO). However, the mechanisms underlying the association of climate indices with yellowfin tuna (YFT) abundance and habitat preference remain unclear. We analysed long-term longline fishery data for YFT and oceanic climate variability index data for 1971–2018. The standardized catch per unit effort (CPUE) of Indo-Pacific Ocean YFT was higher during negative AMO and positive PDO phases. In tropical Pacific Ocean, the trend of YFT habitat preference exhibited seesaw patterns because of the distinct environmental factors influenced by the PDO phase. The PDO changed the environmental parameters throughout the tropical Indian Ocean such that the habitat preference of YFT remained consistent throughout. However, the variations in habitat suitability did not correspond to the distribution or standardized CPUE of YFT throughout the Pacific Ocean during AMO events. Moreover, the changes in habitat suitability had a positive periodicity of 8–16 years with AMO in the Indian Ocean, but revealed opposite trends with the distribution or standardized CPUE of YFT. Our results provide sufficient information to distinguish the variations between PDO phase changing and YFT standardized CPUE/ habitat preference. Furthermore, the AMO phase shift period 60–100 years longer than that of the PDO (20–30 years), and models employing time series of fishery and environmental data must be extended the time period of our study to make the AMO match the fishery data more complete.

Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, thereby increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5–5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Background/Aim: Gout, characterized by acute inflammatory symptoms and monosodium urate crystal deposits in joints, is prevalent among males and the elderly. Total knee arthroplasty (TKA) is a common treatment for knee osteoarthritis (OA), but its impact on the risk of developing gout is unclear. This study examined the risk of gout in patients undergoing TKA. Patients and Methods: Utilizing the TriNetX research network, a retrospective cohort study was conducted on OA patients without prior gout. The TKA cohort was compared to a non-TKA control group using propensity score matching to balance covariates. The primary outcome was the incidence of gout over a five-year follow-up period. Results: The study included 38,834 matched pairs of TKA and non-TKA patients. TKA patients had a 15.6% higher risk of developing gout (HR=1.156; 95%CI=1.042-1.284) compared to controls. Sensitivity analyses confirmed the increased risk across various models and follow-up durations. Conclusion: TKA is associated with a higher risk of developing gout, particularly in females and older adults. Clinicians should monitor and manage gout risk in TKA patients, emphasizing preventive measures and early intervention. Further research is needed to understand the underlying mechanisms and improve patient care post-TKA. [ABSTRACT FROM AUTHOR]

Abstract Chinese medicine (CM) has a long history in the treatment of psoriasis, and its different understanding angle and treatment mode from modern medicine have unique wisdom. In this article, we consulted a large number of literatures and collected data in order to systematically clarify how CM understands psoriasis, including the classification and judgment of syndrome types, the diagnosis and thinking of etiology and pathogenesis, the application of treatment ideas, principles, methods and various prescriptions, and suggestions on patient care, so as to provide a clear CM treatment process and experience for the world clinic. In addition, we analyzed the efficacy and safety through clinical data, and summarize the methods and prescriptions worthy of promotion, so as to provide reference for doctors to prescribe prescriptions and medication. Finally, we found that compared with modern medicine, CM has unique advantages in the treatment of psoriasis, including the uniqueness of syndrome classification, the abundantly and flexibility of treatment ideas. Not only many famous doctors have studied the ideas in ancient books, but also made great efforts to innovate, which has left a lot of valuable experiences for clinical practice. Moreover, a large number of treatment methods, prescriptions and medicines have achieved high effectiveness and safety in clinical practices for many years, which has been proved to be worthy of clinical reference and in-depth research. In addition, we also think about the deficiencies of CM in the treatment of psoriasis and the direction of breakthrough combined with modern medicine. The treatment of psoriasis with CM is worth popularizing, and we hope it can benefit more patients.

BackgroundTaiwan has insufficient nursing resources due to the high turnover rate of health care providers. Therefore, reducing the heavy workload of these employees is essential. Herein, speech transcription, which has various potential clinical applications, was employed for the documentation of nursing records. The requirement of including only one speaker per transcription facilitated data collection and system development. Moreover, authorization from patients was unnecessary. ObjectiveThe aim of this study was to construct a speech recognition system for nursing records such that health care providers can complete nursing records without typing or with only a few edits. MethodsNursing records in Taiwan are mainly written in Mandarin, with technical terms and abbreviations presented in both Mandarin and English. Therefore, the training set consisted of English code-switching information. Next, transfer learning (TL) and meta-TL (MTL) methods, which perform favorably in code-switching scenarios, were applied. ResultsAs of September 2021, the China Medical University Hospital Artificial Intelligence Speech (CMaiSpeech) data set was established by manually annotating approximately 100 hours of recordings from 525 speakers. The word error rate (WER) of the benchmark model of syllable-based TL was 29.54% in code-switching. The WER of the proposed model of syllable-based MTL was 22.20% in code-switching. The test set comprised 17,247 words. Moreover, in a clinical case, the proposed model of syllable-based MTL yielded a WER of 31.06% in code-switching. The clinical test set contained 1159 words. ConclusionsThis paper has two main contributions. First, the CMaiSpeech data set—a Mandarin-English corpus—has been established. Health care providers in Taiwan are often compelled to use a mixture of Mandarin and English in nursing records. Second, an automatic speech recognition system for nursing record document conversion was proposed. The proposed system can shorten the work handover time and further reduce the workload of health care providers.

ObjectiveTo implement an all-day online artificial intelligence (AI)-assisted detection of ST-elevation myocardial infarction (STEMI) by prehospital 12-lead electrocardiograms (ECGs) to facilitate patient triage for timely reperfusion therapy.MethodsThe proposed AI model combines a convolutional neural network and long short-term memory (CNN-LSTM) to predict STEMI on prehospital 12-lead ECGs obtained from mini-12-lead ECG devices equipped in ambulance vehicles in Central Taiwan. Emergency medical technicians (EMTs) from the 14 AI-implemented fire stations performed the on-site 12-lead ECG examinations using the mini portable device. The 12-lead ECG signals were transmitted to the AI center of China Medical University Hospital to classify the recordings as “STEMI” or “Not STEMI”. In 11 non-AI fire stations, the ECG data were transmitted to a secure network and read by available on-line emergency physicians. The response time was defined as the time interval between the ECG transmission and ECG interpretation feedback.ResultsBetween July 17, 2021, and March 26, 2022, the AI model classified 362 prehospital 12-lead ECGs obtained from 275 consecutive patients who had called the 119 dispatch centers of fire stations in Central Taiwan for symptoms of chest pain or shortness of breath. The AI's response time to the EMTs in ambulance vehicles was 37.2 ± 11.3 s, which was shorter than the online physicians' response time from 11 other fire stations with no AI implementation (113.2 ± 369.4 s, P < 0.001) after analyzing another set of 335 prehospital 12-lead ECGs. The evaluation metrics including accuracy, precision, specificity, recall, area under the receiver operating characteristic curve, and F1 score to assess the overall AI performance in the remote detection of STEMI were 0.992, 0.889, 0.994, 0.941, 0.997, and 0.914, respectively. During the study period, the AI model promptly identified 10 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) with a median contact-to-door time of 18.5 (IQR: 16–20.8) minutes.ConclusionImplementation of an all-day real-time AI-assisted remote detection of STEMI on prehospital 12-lead ECGs in the field is feasible with a high diagnostic accuracy rate. This approach may help minimize preventable delays in contact-to-treatment times for STEMI patients who require PPCI.

Abstract Background Chronic kidney disease has been identified as a risk factor affecting stroke prognosis. High-grade carotid artery stenosis (CAS) is associated with distal hemodynamic compromise. The association between the estimated glomerular filtration rate (eGFR) and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between eGFR and outcomes of acute IS patients with high-grade CAS. Methods From January 1, 2007 to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. The eGFR on admission was assessed using the Modification of Diet in Renal Disease Study equation. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between different eGFR levels. Results Among 372 individuals, 76 (20.4%) had an eGFR

Abstract The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24‐GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24‐GCB cells in a dose‐dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24‐GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24‐GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24‐GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

Abstract Background To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA). Methods In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared. The outcome measures of multimodal imaging were evaluated for correlation with BCVA. Results NIR is a good diagnostic tool for detecting either crystalline or sclerotic vessels in BCD. Patients in group 1 tended to have a thinner choroid (P = 0.047) with ellipsoid zone (EZ) disruption (P = 0.011). Calculation of the area under the curve indicated that EZ disruption detected on SD-OCT could be a good predictor of legal blindness in BCD. Conclusion For the diagnosis of BCD, NIR could be a good diagnostic tool. Of the studied imaging modalities, we found that EZ disruption at the fovea were strongly associated with legal blindness, which could be easily assessed by SD-OCT.

Introduction: Tocolytic treatment is beneficial to pregnant women with a risk of premature labor or miscarriage. However, previous reports have shown that progestogen might not be effective and ritodrine may increase the risk of maternal vascular-related diseases. Chinese herbal products (CHP) are used as alternative therapies for pregnant women. The goal was to evaluate the efficacy of combined tocolytic therapy and CHP therapy in pregnancy outcomes for pregnant women in Taiwan.Materials and Methods: We conducted a retrospective cohort study based on the National Health Insurance Research Database. A total of 47,153 pregnant women treated with tocolytics aged 18–50 years from 2001 to 2015 were selected from two million random samples. According to the medical use of tocolytics and CHP, we divided the users into two groups: western medicine (WM) only (n = 40,961) and WM/CHP (n = 6,192) groups. A propensity score (PS)-matched cohort (6,192 pairs) was established based on baseline confounders. All participants were followed up to perinatal outcomes. Conditional logistic regression analysis was used to examine the effects of CHP use on the odds of miscarriage and preterm birth.Results: The adjusted odds ratio (OR) for premature birth in the WM/CHP group (n = 411, 6.64%) was significantly lower than in the WM group (n = 471, 7,61%) (0,86, 95% confidence interval [CI], 0.74–0.99). Further subgroup analysis based on the usage of formulae that activate blood and remove stasis or purgative formulae, the adjusted OR of preterm birth of those using these formulae was significantly lower in the WM/CHP group (n = 215, 6.32%) than that in the WM group (n = 265, 7.77%) (OR: 0.79, 95% CI: 0.65–0.96).Conclusion: We found that the combination of CHP and tocolytics can be beneficial to pregnant women in the prevention of premature birth. Further research is required to investigate causal relationships.

Marine alkaloids have novel structures and antitumor activities. Therefore, we synthesized rhopaladins’ analogs from marine alkaloids rhopaladins A-D and modified their structures to synthesize 4-benzylidene-5-pyrrolidone derivatives. Among the compounds, (2E, 4E)-4-(4-chlorobenzylidene)-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) has high efficiency and less hepatotoxicity, with IC50 values of 4.66, 6.42, 17.66, 15.2, 12.36, 22.4, and 243.2 μM in vitro anti-proliferative activity testing against cervical cancer C-33A, CaSki, SiHa, and HeLa cells, human hepatocarcinoma HepG2 and 7402 cells, and human normal liver LO2 cells, respectively. In particular, RPDPRH has similar activity to cisplatin on human hepatocarcinoma cells, and cisplatin served as a positive control in our study. Next, the apoptosis of HepG2 and 7402 cells induced by RPDPRH at different concentrations was detected by Annexin V/PI flow cytometry. Moreover, the expression of apoptotic proteins was detected by Western blot analysis. Finally, the results showed that RPDPRH could induce apoptosis of hepatocarcinoma cells by regulating Bax and Bcl-2 expressions. In summary, our results indicate that RPDPRH has the potential to serve as an antitumor agent and plays a significant role in future studies.

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10−3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.

Objectives: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. Methods: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer–Lemeshow (H–L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880−0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844−0.916]). Both were externally validated on the H–L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. Conclusion: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

Abstract Background Cytokines are effective molecules of immune reactions. They work in inflammatory sites as well as circulate in the blood. Cytokines in the cerebrospinal fluid have been suggested to be markers of autoimmune encephalitis and reflect disease progression. However, studies on blood cytokines in autoimmune encephalitis are scarce. We report a case presenting with serial changes in blood cytokine levels in a male patient with anti-contactin-associated protein 2 (Caspr2) encephalitis. Case presentation A 61-year-old man without systemic disease presented with ataxia and speech disturbance 1 week. After admission, he further developed visual hallucinations, psychosis, and consciousness deterioration. Brain magnetic resonance imaging and infection and tumor surveillances were negative. 18F-fluorodeoxyglucose positron emission tomography of brain revealed frontal and occipital hypometabolism and anterior cingulate gyrus and mesial temporal hypermetabolism. Autoimmune studies confirmed Caspr2 antibodies in his blood. After receiving a diagnosis of anti-Caspr2 encephalitis, the patient received steroids, plasmapheresis, and zonisamide. He recovered well and was totally independent 6 months after disease onset. A cytokine profiler array kit was used to investigate neuroimmune mechanisms during the disease course. Several cytokines showed significant changes in plasma levels, such as B cell activating factor for B cell proliferation; thymus and activation-regulated chemokine for T cell chemoattraction; soluble CD40 ligand for Th2 cell mediation; C5/C5a for complement activation; brain-derived neurotrophic factor for neuronal survival response; and dipeptidyl peptidase 4, retinol binding protein, dickkopf-related protein, and epidermal growth factor for response to environmental provocation. The concentration of cytokines was verified using Luminex multiplexing assay. Conclusions Due to their easy accessibility, blood cytokines are potential biomarkers of autoimmune encephalitis. Based on the investigating platform of this single case study, future larger scale studies are warranted.

Abstract Background Bone tumors are often treated with intralesional curettage. High-speed burring, an adjuvant therapy, was performed to maximize the tumor cell killing; however, tumor recurrence might still occur, which may be caused by residual tumor or local tumor spread during surgery. Methods A porcine cadaver (femur) was utilized to determine whether the use of a high-speed burr causes bone cement spray. To mimic residual tumor after curettage, luminescent cement was smeared on two locations of the bone cavity, the wall and the bottom. The cavity in the femoral bone was then placed in the middle of a sheet of drawing paper featuring 10 cm, 20 cm, and 30 cm concentric circles. The luminescent cement was then burred totally with a high-speed burr. Results The intensity of the area in the wall in circle I was 72.6% ± 5.8%; within circle II, it was 22.1% ± 4.2%; and within circle III, it was 5.4% ± 1.5%. The intensity of the area within the bottom of the femoral bone within circle I was 66.5% ± 6.1%, within circle II was 28.1 ± 4.8%, and within circle III, it was 5.4% ± 1.4%. The amount of luminescent cement seeding decreased with distance, but there was no difference while burring at different locations of the bone cavity. Under the handpiece cover, a greater amount of cement spray was retained in circle I during burring of the cement in the bottom of the cavity and less was sprayed out in circle III. Conclusions High-speed burring may cause explosive bone cement spray, which could extend to 20 cm. The intensities of spray did not decrease, even when the handpiece cover was used. The wide range of bone cement spray caused by high-speed burr was inspected in this pilot study, which may lead to tumor seeding. Level of evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Mixed use has been extensively applied as an urban planning principle and hinders the study of single urban functions. To address this problem, it is worth decomposing the mixed use. Inspired by the concept of spectral unmixing in remote sensing applications, this paper proposes a framework for mixed-use decomposition based on big geo-data. Mixed-use decomposition in terms of human activities differs from traditional land use research, and it is more reasonable to infer the actual urban function of land. The framework consists of four steps, namely temporal activity signature extraction, urban function base curve extraction, mixed-use decomposition, and result validation. First, the temporal activity signatures (TASs) of each zone are extracted as the proxy of human activity patterns. Second, the diurnal TASs of routine activities are extracted as urban function base curves (i.e. endmembers). Third, a linear decomposition model is used to decompose the mixed use and obtain multiple results (urban function composition, dynamic activity proportions, and the mixing index). Finally, result validation strategies are concluded. This framework offers method extensibility and has few requirements for the input data. It is validated by means of a case study of Beijing, based on a social media check-in dataset.

Objectives: This study evaluated disc diffusion tests and agar screening for detecting mecA-mediated oxacillin resistance in Staphylococcus lugdunensis (S. lugdunensis). Methods: Staphylococcus lugdunensis isolates (n = 179) from diverse sources in Hong Kong during 1998–2018 were investigated by disc diffusion tests (cefoxitin and oxacillin) and inoculation onto oxacillin (1 μg/mL and 2 μg/mL) and chromID methicillin-resistant Staphylococcus aureus (MRSA) agars. The results were compared with mecA PCR as the reference. Isolates with discordant results were further tested by MIC and penicillin-binding protein 2a (PBP2a) assays. Results: Cefoxitin and oxacillin zone diameters were not distributed in ways that allowed reliable division of the mecA-positive (n = 52) and mecA-negative (n = 127) isolates. On applying the 2019 Clinical Laboratory Standards Institute (CLSI) M100 breakpoints for cefoxitin disc results, there was 88% categorical agreement (CA) and 40% very major error (VME). Screening using 2 μg/mL oxacillin agar reliably differentiated mecA-positive and mecA-negative isolates (100% CA) without any major error (ME) or VME results. The performance of screening using 1 μg/mL oxacillin agar or ChromID MRSA agar was variable (74–89% CA, 0–38% ME and 0–37% VME). The mecA-positive isolates (n = 21) that could not be detected by the cefoxitin disc test were further characterised. The cefoxitin MIC for all 21 isolates was ≤4 μg/mL. Twenty isolates had an oxacillin MIC of 1–2 μg/mL and one had an oxacillin MIC of 4 μg/mL. All had positive PBP2a results and were typed as clonal cluster 27/SCCmec V. Conclusions: These findings highlight the need to evaluate phenotypic methods using mecA-positive S. lugdunensis with different oxacillin resistance phenotypes.

Abstract Background To evaluate the feasibility of a surgical technique using a sub-perfluoro-n-octane (PFO) injection of ocular viscoelastic device (OVD) to stabilize inverted internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment (MHRD). Methods This study was a retrospective, consecutive, interventional case series. Patients who underwent MHRD surgery with sub-PFO injection of OVD to stabilize inverted ILM flap onto the macular hole (MH) were reviewed. The color fundus and optical coherence tomography (OCT) images were collected and evaluated. The best-corrected visual acuity (BCVA) before and after surgery were compared as the functional outcome. Results The study included 8 eyes of 8 consecutive patients (mean age: 61.8 ± 7.1 years; mean follow-up period: 9.0 ± 2.5 months). All eyes (100%) achieved successful MH closure; 7 eyes (87.5%) demonstrated complete retinal reattachment, and 1 eye (12.5%) had minimal residual subretinal fluid parafoveally. Of the 8 patients, 7 patients (87.5%) had achieved improvement in BCVA after the primary surgery, whereas 1 eye remained stable. The average BCVA before and after the surgery at the last visit improved from 20/843 (1.63 ± 0.48 logMAR) to 20/200 (1.00 ± 0.39 logMAR) (P = 0.016). Anatomically, near-normal foveal contour was noted in five (62.5%) eyes at the final follow-up. Conclusions The use of sub-PFO injection of OVD in MHRD surgery could stabilize inverted ILM flaps, achieve good anatomical results and improve postoperative BCVA.

In this study, a polyvinylidene fluoride (PVDF)/graphene nanoplatelet (GNP) micro-nanocomposite membrane was fabricated through electrospinning technology and was employed in the fabrication of a fiber-reinforced polymer composite laminate. Some glass fibers were replaced with carbon fibers to serve as electrodes in the sensing layer, and the PVDF/GNP micro-nanocomposite membrane was embedded in the laminate to confer multifunctional piezoelectric self-sensing ability. The self-sensing composite laminate has both favorable mechanical properties and sensing ability. The effects of different concentrations of modified multiwalled carbon nanotubes (CNTs) and GNPs on the morphology of PVDF fibers and the β-phase content of the membrane were investigated. PVDF fibers containing 0.05% GNPs were the most stable and had the highest relative β-phase content; these fibers were embedded in glass fiber fabric to prepare the piezoelectric self-sensing composite laminate. To test the laminate’s practical application, four-point bending and low-velocity impact tests were performed. The results revealed that when damage occurred during bending, the piezoelectric response changed, confirming that the piezoelectric self-sensing composite laminate has preliminary sensing performance. The low-velocity impact experiment revealed the effect of impact energy on sensing performance.

Three typhoons, Meranti, Malakas, and Megi, occurred successively in eastern Taiwanese waters in September 2016, causing extreme waves (significant wave height > 10.0 m), and these events were selected to investigate the effect of model grid resolution and wave–wave interaction on simulating typhoon-driven waves. The WAVEWATCH III (WW3) model, with 0.50 deg, 0.25 deg, 0.20 deg, 0.10 deg, and 0.05 deg grid resolutions, and two reanalysis wind fields were adopted to simulate ocean waves during these three typhoons. The results indicated that the exertion of the Climate Forecast System version 2 (CFSv2) winds over the WW3 model with 0.10 deg grid resolution yielded optimum simulations of typhoon waves in a compromise between accuracy and elapsed time. In the present study, the WW3 model modeled nonlinear wave–wave interactions using discrete interaction approximation (DIA). The numerical experiments revealed that the underestimations of typhoon waves were significant when the WW3 model excluded nonlinear wave–wave interactions, especially when employing a higher grid resolution. This study also found that the WW3 model is superior to the Wind Wave Model III (WWM-III) using the CFSv2 winds because the WWM-III tended to overestimate the extreme waves in all three of these eastern Taiwan typhoon events that occurred in September 2016.