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Abstract We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

Abstract Microvascular dysfunction is the underlying pathological process in many systemic diseases. However, investigation into its pathogenesis is impeded by the accessibility and complexity of the microvasculature within different organs, particularly for the central nervous system. The retina as an extension of the cerebrum provides a glimpse into the brain through which the microvasculature can be observed. Two major questions remain unanswered: How do the microvessels regulate spatial and temporal delivery to satisfy the varying cellular demands, and how can we quantify blood perfusion in the 3D capillary network? Here, quantitative measurements of red blood cell (RBC) speed in each vessel in the field were made in the in vivo rat retinal capillary network using an ultrafast confocal technique with fluorescently labelled RBCs. Retinal RBC speed and number were found to vary remarkably between microvessels ranging from 215 to 6641 microns per second with significant variations spatially and temporally. Overall, the RBC speed was significantly faster in the microvessels in the superficial retina than in the deep retina (estimated marginal means of 2405 ± 238.2 µm/s, 1641 ± 173.0 µm/s respectively). These observations point to a highly dynamic nature of microvasculature that is specific to its immediate cellular environment and is constantly changing.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Abstract In today’s rapidly changing economy, efficient lifestyle has become the current situation of most mobile product users. With the development of performance tools and technologies, a fast lifestyle has brought more wealth and opportunities to users. The slow pace and fluctuating time are indirect income losses, which cause user anxiety to some extent. When the waiting time exceeds the user’s waiting threshold, users would experience negative emotions, such as boredom, anxiety and anger, and product satisfaction would drop significantly. Therefore, by analyzing the uniqueness of mobile Internet products and the characteristics of users, this paper studied the reasons and influencing factors of product interactive waiting, and then used machine learning algorithm to analyze the cost function of interactive waiting experience. Finally, the corresponding interactive waiting experience design strategy was proposed. By comparison, the user experience after product interaction optimization design was 8.4% higher than that before product interaction optimization design, and the user frequency was also 14.7% higher after optimization design. In short, user experience plays an important role in product interaction design.

Abstract Background Intertwined association between infectious gastroenteritis (IGE) and inflammatory bowel disease (IBD) has not been investigated clearly. We aimed to examine the bidirectional association between IGE and IBD. Methods A bidirectional study using the Taiwan National Health Insurance Research Database was designed. Through a case-control design, we identified 2899 new IBD cases during 2006–2017 and matched to 28,990 non-IBD controls. We used conditional logistic regression model to estimate odds ratios (OR) of IBD for previous IGE in different exposure time-windows within 5-years before IBD diagnosis and Poisson regression model to estimate incidence rate ratio (IRR) of subsequent IGE for IBD group to non-IBD group. Results The mean age at the initial IBD diagnosis was 41 years. More IBD patients (21.49%) than controls (12.60%) had been exposed to IGE during > 6 months to 5 years before IBD diagnosis, the OR of IBD for IGE was 1.89 [95% confidence interval: 1.69–2.11]. Excess OR decreased as IGE exposure time before the index date increased. More IGE episodes were associated with additional increase in IBD risk (OR: 1.64, 2.19, 2.57, 3.50, and 4.57 in patients with 1, 2, 3, 4, and ≥ 5 IGE episodes, respectively). The IRR of having IGE for IBD group to non-IBD group was 2.42 before IBD diagnosis and increased to 5.74 after IBD diagnosis. Conclusions These findings suggested an IGE-IBD bidirectional association. More attention is needed for physicians to develop preventive strategies and be aware of the higher risk of subsequent IGE in IBD patients.

Abstract This study identifies seasonally-reversed trends in Kuroshio strength and sea surface temperatures (SSTs) within the western North Pacific (WNP) since the 1990s, specifically in the 22° N–28° N region. These trends are characterized by increases during summer and decreases during winter. The seasonally-reversed trends are a result of the asymmetric responses of the WNP to a shift towards the positive phase of the Atlantic multidecadal oscillation (AMO) around the same period. The positive AMO induces an anomalous descent over the North Pacific during summer, leading to the direct strengthening of the gyre. However, during winter, it triggers an anomalous descent over the tropical Pacific, which excites a poleward wavetrain impacting the WNP and causing gyre weakening. The associated responses of the East Asian monsoon and China Coastal Current contribute to the observed seasonally-reversed SST trends. It is noteworthy that the seasonally-reversed trends in gyre strength and SSTs are predominantly observed north of 20° N in the WNP. This limitation arises because the anomalous cyclone within the winter poleward wavetrain is located north of this latitude boundary. Specifically, the clearest trends in gyre strength are observed in the northern segment of the Kuroshio, while the manifestation of SST trends in the Taiwan Strait could potentially be attributed to the influence and enhancement of the East Asian monsoon and the China Coastal Current. Due to the limited length of observational data, statistical significance of some of the signals discussed is rather limited. A CESM1 pacemaker experiments is further conducted to confirm the asymmetric responses of the North Pacific to the AMO between the summer and winter seasons.

Abstract An adequate blood supply to meet the energy demands is essential for any tissue, particularly for high energy demand tissues such as the retina. A critical question is: How is the dynamic match between neuronal demands and blood supply achieved? We present a quantitative assessment of temporal and spatial variations in perfusion in the macular capillary network in 10 healthy human subjects using a non-invasive and label-free imaging technique. The assessment is based on the calculation of the coefficient of variation (CoV) of the perfusion signal from arterioles, venules and capillaries from a sequence of optical coherence tomography angiography images centred on the fovea. Significant heterogeneity of the spatial and temporal variation was found within arterioles, venules and capillary networks. The CoV values of the capillaries and smallest vessels were significantly higher than that in the larger vessels. Our results demonstrate the presence of significant heterogeneity of spatial and temporal variation within each element of the macular microvasculature, particularly in the capillaries and finer vessels. Our findings suggest that the dynamic match between neuronal demands and blood supply is achieved by frequent alteration of local blood flow evidenced by capillary perfusion variations both spatially and temporally in the macular region.

BackgroundPrevious studies evaluating the association between prediabetes and depression have shown inconsistent results. Consequently, the aim of the systematic review and meta-analysis was to investigate whether prediabetes is associated with depression in the general population.MethodsRelevant observational studies were obtained by searching the Medline, Web of Science, and Embase databases. A random-effects model was utilized to pool the results by incorporating the influence of heterogeneity. Multiple subgroup analysis was performed to evaluate the influence of the study characteristics on the outcome.ResultsSixteen large-scale cross-sectional studies involving 322,863 participants were included. Among the total participants, 82,154 (25.4%) had prediabetes. The pooled results showed that prediabetes was associated with a higher prevalence of depression in this population (odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.05 to 1.28, p = 0.003; I2 = 58%). Subgroup analysis showed a stronger association between prediabetes and depression in younger subjects ( 0.05).ConclusionsPrediabetes may be associated with a slightly higher prevalence of depression in the general population, particularly in subjects aged

Even with the powerful statistical parameters derived from the Extreme Gradient Boost (XGB) algorithm, it would be advantageous to define the predicted accuracy to the level of a specific case, particularly when the model output is used to guide clinical decision-making. The probability density function (PDF) of the derived intracranial pressure predictions enables the computation of a definite integral around a point estimate, representing the event's probability within a range of values. Seven hold-out test cases used for the external validation of an XGB model underwent retinal vascular pulse and intracranial pressure measurement using modified photoplethysmography and lumbar puncture, respectively. The definite integral ±1 cm water from the median (DIICP) demonstrated a negative and highly significant correlation (-0.5213±0.17, p< 0.004) with the absolute difference between the measured and predicted median intracranial pressure (DiffICPmd). The concordance between the arterial and venous probability density functions was estimated using the two-sample Kolmogorov-Smirnov statistic, extending the distribution agreement across all data points. This parameter showed a statistically significant and positive correlation (0.4942±0.18, p< 0.001) with DiffICPmd. Two cautionary subset cases (Case 8 and Case 9), where disagreement was observed between measured and predicted intracranial pressure, were compared to the seven hold-out test cases. Arterial predictions from both cautionary subset cases converged on a uniform distribution in contrast to all other cases where distributions converged on either log-normal or closely related skewed distributions (gamma, logistic, beta). The mean±standard error of the arterial DIICP from cases 8 and 9 (3.83±0.56%) was lower compared to that of the hold-out test cases (14.14±1.07%) the between group difference was statistically significant (p

Abstract This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P

Abstract Objective Using the novel imaging method of high-speed modified photoplethysmography we measured the retinal venous pulse wave velocity in a single case. Results A healthy 30-year-old subject underwent high-speed modified photoplethysmography (120 frames per second) with simultaneous ophthalmodynamometry at 26 Meditron units. A video of the optic nerve was analyzed using custom software. A harmonic regression model was fitted to each pixel in the time series and used to quantify the retinal vascular pulse wave parameters. Retinal venous pulsation at the optic disc was observed as a complex dynamic wall motion, whereas contraction commenced at a point in the vein at the center of the optic disc, and progressed centrifugally. The empirically estimated retinal venous pulse wave velocity at this segment was approximately 22.24694 mm/s. This measurement provides an estimate for future studies in the field.

Abstract Loss of TGF-β-mediated growth suppression is a major contributor to the development of cancers, best exemplified by loss-of-function mutations in genes encoding components of the TGF-β signaling pathway in colorectal and pancreatic cancers. Alternatively, gain-of-function oncogene mutations can also disrupt antiproliferative TGF-β signaling. However, the molecular mechanisms underlying oncogene-induced modulation of TGF-β signaling have not been extensively investigated. Here, we show that the oncogenic BCR-ABL1 of chronic myelogenous leukemia (CML) and the cellular ABL1 tyrosine kinases phosphorylate and inactivate Smad4 to block antiproliferative TGF-β signaling. Mechanistically, phosphorylation of Smad4 at Tyr195, Tyr301, and Tyr322 in the linker region interferes with its binding to the transcription co-activator p300/CBP, thereby blocking the ability of Smad4 to activate the expression of cyclin-dependent kinase (CDK) inhibitors and induce cell cycle arrest. In contrast, the inhibition of BCR-ABL1 kinase with Imatinib prevented Smad4 tyrosine phosphorylation and re-sensitized CML cells to TGF-β-induced antiproliferative and pro-apoptotic responses. Furthermore, expression of phosphorylation-site-mutated Y195F/Y301F/Y322F mutant of Smad4 in Smad4-null CML cells enhanced antiproliferative responses to TGF-β, whereas the phosphorylation-mimicking Y195E/Y301E/Y322E mutant interfered with TGF-β signaling and enhanced the in vivo growth of CML cells. These findings demonstrate the direct role of BCR-ABL1 tyrosine kinase in suppressing TGF-β signaling in CML and explain how Imatinib-targeted therapy restored beneficial TGF-β anti-growth responses.

Abstract Background Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage. Methods C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a −/− stat1 −/− ) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12 −/− stat1 −/− ) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A. Results Compared to experiments conducted in ZIKV-infected stat1 −/− mice, infected clec5a −/− stat1 −/− mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a −/− stat1 −/− mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage. Conclusions Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.

Objective: The aim of this study was to synthesize the available evidence on the clinical efficacy of different relaxation exercises on intraocular pressure (IOP) reduction. Methods: A systemic search of PubMed, Embase, Cochrane CENTRAL, and Web of Science was undertaken from the earliest record to 10 April 2024. Peer-reviewed studies that reported on healthy individuals and glaucoma patients engaging in relaxation exercises for at least three weeks were included. The primary outcome was changes in IOP levels from baseline, before the commencement of relaxation exercises, to post-exercise. Our statistical analysis employed a random-effects model, with effect sizes reported using Hedges’ g. Results: Twelve studies were included, totaling 764 eyes (mean participant age ranging from 21.07 to 69.50 years). Relaxation exercises significantly reduced IOP, with Hedges’ g being −1.276 (95% CI: −1.674 to −0.879) and I2 = 84.4%. Separate subgroup analyses showed that breathing exercises (Hedges’ g = −0.860, p < 0.0001), mindfulness-based stress reduction (MBSR) (Hedges’ g = −1.79, p < 0.0001), and ocular exercises (Hedges’ g = −0.974, p < 0.0001) were associated with reduced IOP levels. The reduction in IOP following the relaxation exercises was found to be associated with baseline IOP either greater than (Hedges’ g = −1.473, p < 0.0001) or less than 21 mmHg (Hedges’ g = −1.22, p < 0.0001). Furthermore, this effect persisted with follow-up durations of less than (Hedges’ g = −1.161, p < 0.0001) and more than one month (Hedges’ g = −1.324, p < 0.0001). Conclusions: The current meta-analysis indicates that relaxation exercises can significantly reduce IOP levels. Relaxation exercises are a potential class of novel treatments for glaucoma patients that deserve further evaluation.

Summary: Background: Dengue virus outbreaks are increasing in number and severity worldwide. Viral transmission is assumed to require a minimum time period of viral replication within the mosquito midgut. It is unknown if alternative transmission periods not requiring replication are possible. Methods: We used a mouse model of dengue virus transmission to investigate the potential of mechanical transmission of dengue virus. We investigated minimal viral titres necessary for development of symptoms in bitten mice and used resulting parameters to inform a new model of dengue virus transmission within a susceptible population. Findings: Naïve mice bitten by mosquitoes immediately after they took partial blood meals from dengue infected mice showed symptoms of dengue virus, followed by mortality. Incorporation of mechanical transmission into mathematical models of dengue virus transmission suggest that this supplemental transmission route could result in larger outbreaks which peak sooner. Interpretation: The potential of dengue transmission routes independent of midgut viral replication has implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes. Funding: This study was funded by grants from the National Health Research Institutes, Taiwan (04D2-MMMOST02), the Human Frontier Science Program (RGP0033/2021), the National Institutes of Health (1R01AI143698-01A1, R01AI151004 and DP2AI152071) and the Ministry of Science and Technology, Taiwan (MOST104-2321-B-400-016).

Abstract Background Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. Methods We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. Results Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. Conclusions Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks.

Abstract We propose a hetero-nano-fin structure to further improve the efficiency of Pancharatnam–Berry phase metasurfaces. Two hetero-nano-fin types, MgF2/GaN and MgF2/Nb2O5, were investigated. The overall polarization conversion efficiency (PCE) improved from 52.7 to 54% for the MgF2/GaN nano-fin compared with the bare GaN nano-fin. The overall PCE of the Nb2O5 nano-fin was 1.7 times higher than that of the GaN nano-fin. The overall PCE improved from 92.4% up to 96% after the application of MgF2 antireflection. Moreover, the antireflection improves efficiency by an average of 4.3% in wavelengths from 450 to 700 nm. Although the increment of energy seems minimal, antireflection is crucial for a metasurface, not only enhancing efficiency but also reducing background signal of a meta-device.

Abstract Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial‐based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial‐based gene delivery systems. Furthermore, the current applications of biomaterial‐based gene therapy are summarized.

Abstract The Indian and Pacific Oceans surround the Maritime Continent (MC). Major modes of sea surface temperature variability in both oceans, including the Indian Ocean Dipole (IOD) and El Niño–Southern Oscillation (ENSO), can strongly affect precipitation on the MC. The prevalence of fires in the MC is closely associated with precipitation amount and terrestrial water storage in September and October. Precipitation and terrestrial water storage, which is a measurement of hydrological drought conditions, are significantly modulated by Indian Ocean Dipole (IOD) and El Niño events. We utilize long-term datasets to study the combined effects of ENSO and the IOD on MC precipitation during the past 100 years (1900–2019) and find that the reductions in MC precipitation and terrestrial water storage are more pronounced during years when El Niño and a positive phase of the IOD (pIOD) coincided. The combined negative effects are produced mainly through an enhanced reduction of upward motion over the MC. Coincident El Niño-pIOD events have occurred more frequently after 1965. However, climate models do not project a higher occurrence of coincident El Niño-pIOD events in a severely warming condition, implying that not the global warming but the natural variability might be the leading cause of this phenomenon.

Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. Patients with DM have a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in dengue virus (DENV) infection, we used high-glucose (HG) treatment and showed that HG increased viral protein expression and virion release but had no effects on the early stages of viral infection. After HG stimulation, DENV–firefly luciferase–transfected assay and cellular replicon–based assay indicated increased viral translation, whereas using the glucose uptake inhibitor phloretin blocked this effect. HG treatment increased the translational factor poly(A)-binding protein (PABP) in a glucose transporter–associated, PI3K/AKT-regulated manner. Silencing PABP significantly decreased HG-prompted virion production. HG enhanced the formation of the PABP–eukaryotic translation initiation factor 4G complex, which is regulated by protein–disulfide isomerase. Hyperglycemia increased PABP expression, mortality rate, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.

IntroductionTo investigate the association of blepharitis and ischemic stroke.MethodsThis nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis.Results424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis.ConclusionsPatients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.

BackgroundShenqi Fuzheng injection (SQFZ) combined with chemotherapy can sensitize tumour cells. However, the mechanisms underlying SQFZ's effects remain unknown. In human breast cancer cell lines and M2 macrophages, we showed that SQFZ was a significantly potent agent of sensitization.MethodsThe human breast cancer cell line, MDA-MB-231/DDP, and the human acute leukaemia mononuclear cell line, THP-1, were used. MDA-MB-231/DDP breast cancer xenografts were established to monitor tumour growth. Resistance-associated proteins were examined by western blotting. Levels of cytokines and chemokines were detected by ELISA. Cell viability was measured using the MTT assay. Apoptosis was detected by flow cytometric analysis.ResultsSQFZ significantly enhanced the capability of cisplatin to reduce tumour mass. SQFZ and cisplatin decreased the expression of CD206 by 1.89-fold and increased that of CD86 by 1.76-fold as compared to cisplatin alone. The levels of PGE2, IL-6, and CCL1 decreased significantly, and the activation of p-PI3K and the expressions of P-gp and ABCG2 were also inhibited by SQFZ in combination with cisplatin treatment in vivo. The survival following cisplatin administration of 60 μM and 120 μM reduced significantly in the presence of SQFZ in MDA-MB-231/DDP and M2 co-cultured cells. IGF-1, a PI3K activator, combined with SQFZ weakened the effects of SQFZ-induced apoptosis from 28.7% to 10.5%. The effects of IGF-1 on increasing the expressions of P-gp, ABCG2, and Bcl-2, and decreasing that of Bax were reversed by SQFZ.ConclusionOur findings provide evidence that SQFZ is a potential therapeutic drug for cancer therapy.

Background: Surgery in elder patients with intermural fibroids delays pregnancy, and GnRH-a can shrink uterine fibroids to a certain extent; therefore, for geriatric patients with fibroids, determining whether GnRH-a pretreatment before frozen–thawed embryo transfer (FET) can improve its success rate remains to be studied. We conducted this study to research whether GnRH-a pretreatment before hormone replacement treatment (HRT) could optimize the reproductive outcomes compared with others preparations in geriatric patients with intramural fibroids. Methods: According to the endometrial preparation, patients were divided into a GnRH-a–HRT group, a HRT group and a natural cycle (NC) group. The live birth rate (LBR) was the first outcome, and the clinical pregnancy outcome (CPR), the miscarriage rate, the first trimester abortion rate and the ectopic pregnancy rate were the secondary outcomes. Results: A total of 769 patients (aged 35 years or older) were included in this study. No significant difference was observed in the live birth rate (25.3% vs. 17.4% vs. 23.5%, p = 0.200) and the clinical pregnancy rate (46.3% vs. 46.1% vs. 55.4%, p = 0.052) among the three endometrial preparation regimens. Conclusion: In this study, for the geriatric patient with the intramural myoma, the pretreatment with GnRH-a did not show any advantage over the NC and HRT preparation groups before the FET, and the LBR was not significantly increased.

After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total of 38,075 students in universities in Kaohsiung area undergoing entrance examinations between July 2006 to September 2020 were included. Seroprevalence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) status and laboratory data were collected. The seropositive rate of HBsAg was less than 1% for students born after 1991. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly higher, and body mass index (BMI) was significantly lower in HBV carriers compared to those who were not carriers (all p < 0.001). Multivariate logistic regression showed that age, male, higher BMI, and positive HBsAg were risk factors of abnormal ALT value. A decrease in the positive rate of anti-HBs which was significantly higher in the cohort of plasma-derived vaccines than recombinant vaccines was found. We concluded that there were decreasing trends in seropositive rates of HBsAg and anti-HBs for students of the college-aged population in the Kaohsiung area. The status of HBsAg was a predictive factor of abnormal ALT levels. The period effect on anti-HBs seropositivity for DNA recombinant vaccine somehow existed.

PurposeTo compare the retinal vascular pulsatile characteristics in subjects with normal (ICPn) and high (ICPh) intracranial pressure and quantify the interactions between intraocular pressure, intracranial pressure, and retinal vascular pulse amplitude in the Fourier domain.Materials and methodsTwenty-one subjects were examined using modified photoplethysmography with simultaneous ophthalmodynamometry. A harmonic regression model was fitted to each pixel in the time-series, and used to quantify the retinal vascular pulse wave parameters including the harmonic regression wave amplitude (HRWa). The pulse wave attenuation was measured under different ranges of induced intraocular pressure (IOPi), as a function of distance along the vessel (VDist). Intracranial pressure (ICP) was measured using lumbar puncture. A linear mixed-effects model was used to estimate the correlations between the Yeo-Johnson transformed harmonic regression wave amplitude (HRWa-YJt) with the predictors (IOPi, VDist and ICP). A comparison of the model coefficients was done by calculating the weighted Beta (βx) coefficients.ResultsThe median HRWa in the ICPn group was higher in the retinal veins (4.563, interquartile range (IQR) = 3.656) compared to the retinal arteries (3.475, IQR = 2.458), pConclusionThe retinal vascular pulsation characteristics in the ICPh group showed high retinal arterial and low venous pulsation amplitudes. Interactions between retinal vascular pulsation amplitude and ICP suggest that the Fourier sine coefficient bn1 reflects the retinal vascular response to the ICP wave. Although a matrix of regression lines showed high linear characteristics, the low model explanatory power precludes its use as a predictor of ICP. These results may guide future predictive modelling in non-invasive estimation of ICP using modified photoplethysmography.

The ideal Intracranial pressure (ICP) estimation method should be accurate, reliable, cost-effective, compact, and associated with minimal morbidity/mortality. To this end several described non-invasive methods in ICP estimation have yielded promising results, however the reliability of these techniques have yet to supersede invasive methods of ICP measurement. Over several publications, we described a novel imaging method of Modified Photoplethysmography in the evaluation of the retinal vascular pulse parameters decomposed in the Fourier domain, which enables computationally efficient information filtering of the retinal vascular pulse wave. We applied this method in a population of 21 subjects undergoing lumbar puncture manometry. A regression model was derived by applying an Extreme Gradient Boost (XGB) machine learning algorithm using retinal vascular pulse harmonic regression waveform amplitude (HRWa), first and second harmonic cosine and sine coefficients (an1,2, bn1,2) among other features. Gain and SHapley Additive exPlanation (SHAP) values ranked feature importance in the model. Agreement between the predicted ICP mean, median and peak density with measured ICP was assessed using Bland-Altman bias±standard error. Feature gain of intraocular pressure (IOPi) (arterial = 0.6092, venous = 0.5476), and of the Fourier coefficients, an1 (arterial = 0.1000, venous = 0.1024) ranked highest in the XGB model for both vascular systems. The arterial model SHAP values demonstrated the importance of the laterality of the tested eye (1.2477), which was less prominent in the venous model (0.8710). External validation was achieved using seven hold-out test cases, where the median venous predicted ICP showed better agreement with measured ICP. Although the Bland-Altman bias from the venous model (0.034±1.8013 cm water (p

Multiple vaccines are now being used across the world, and several studies have described cases of corneal graft rejection following the administration of the COVID-19 vaccine. The purpose of this article is to review the corneal adverse event that occurred following COVID-19 vaccine administration. The literature search was conducted in March 2022 using MEDLINE, PubMed, and the Cochrane Database of Systematic Reviews. A total of 27 articles, including 37 cases, have documented corneal adverse events that occurred following COVID-19 vaccination. The mean age was 60 ± 14.9 years (range, 27–83 years). The most common events were acute corneal graft rejection (n = 21, 56.8%), followed by herpes zoster ophthalmicus (n = 11, 29.7%) and herpes simplex keratitis (n = 2, 5.4%). The mean time from vaccination to the event was 10 ± 8.5 days (range, 1–42 days) after the first or second dose of vaccine. All patients with corneal graft rejection, immune-mediated keratolysis, and peripheral ulcerative keratitis (PUK) (n = 24, 64.9%) were managed topically with or without oral corticosteroids. Patients with herpes zoster ophthalmicus and herpes simplex keratitis were managed with oral antiviral agents. Two patients received penetrating keratoplasty due to keratolysis after invalid topical treatment. Disease resolution was noted in 29 patients (78.3%), whereas 3 (8.1%) had persistent corneal edema after graft rejection, 1 (2.7%) had corneal infiltration after HZO, and 4 (10.8%) were not mentioned in the articles. Corneal adverse events could occur after COVID-19 vaccination. After timely treatment with steroids or antiviral agents, most of the events were mild and had a good visual outcome. Administrating or increasing steroids before vaccination may be useful for the prevention of corneal graft rejection. However, the prophylactic use of antiviral treatments in patients with a herpes viral infection history is not recommend.

Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case–control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients’ quality of life.

Reproductive tract inflammation is considered an important cause of male infertility. Increased leukocytes in semen can produce many reactive oxygen species (ROS), which affect sperm function. The aim of this study is to identify the main source of ROS in seminal plasma and to assess the effect of ROS on leukocytes. Semen samples ( n = 20) with leukocyte concentration >1 × 10 6 were collected from a male infertility clinic. This study mainly compares the sperm function parameters of the normal group and the semen white blood cell group >1 × 10 6 . The results identified that ROS in semen was closely related to sperm function parameters, and CD45 + leucocytes were the main source of ROS. Compared with the control group, the concentration of IL-2, IL-4, IL-6, IFN-γ, and TNF-α was higher in the experimental group. Leukocytes in semen may regulate the secretion of ROS through the mammalian target of rapamycin (mTOR) pathway. A considerable amount of ROS can upregulate the expression of IL-6 in leukocytes via the nuclear factor kappa-B (NF-kB) pathway.

Background: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. Methods: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5 years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established. Findings: Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16–13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets. Interpretation: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.

Objective: Conventional open spinal surgery of adult scoliosis can be performed from anterior, posterior, or combined approach. Minimally invasive spine surgery (MISS) was developed for the purpose of reducing the undesirable effects and complications. This review aimed to make a brief summary of recent studies of the approach and clinical outcomes of MISS in adult scoliosis. Data Sources: We conducted a systematic search from PubMed, Medline, EMBASE, and other literature databases to collect reports of surgical methods and clinical outcomes of MISS in treatment of adult scoliosis. Those reports were published up to March 2017 with the following key terms: “minimally invasive,” “spine,” “surgery,” and “scoliosis.” Study Selection: The inclusion criteria of the articles were as followings: diagnosed with adult degenerative scoliosis (DS) or adult idiopathic scoliosis; underwent MISS or open surgery; with follow-up data. The articles involving patients with congenital scoliosis or unknown type were excluded and those without any follow-up data were also excluded from the study. The initial search yielded 233 articles. After title and abstract extraction, 29 English articles were selected for full-text review. Of those, 20 studies with 831 patients diagnosed with adult DS or adult idiopathic scoliosis were reviewed. Seventeen were retrospective studies, and three were prospective studies. Results: The surgical technique reported in these articles was direct or extreme lateral interbody fusion, axial lumbar interbody fusion, and transforaminal lumbar interbody fusion. Among the clinical outcomes of these studies, the operated levels was 3–7, operative time was 2.3–8.5 h. Both the Cobb angle of coronal major curve and evaluation of Oswestry Disability Index and Visual Analog Scale decreased after surgery. There were 323 complications reported in the 831 (38.9%) patients, including 150 (18.1%) motor or sensory deficits, and 111 (13.4%) implant-related complications. Conclusions: MISS can provide good radiological and self-evaluation improvement in treatment of adult scoliosis. More prospective studies will be needed before it is widely used.

UNC-13 proteins play an essential role in synaptic transmission by recruiting synaptic vesicles (SVs) to become available for release, which is termed SV priming. Here we show that the C2A domain of UNC-13L, like the corresponding domain in mammalian Munc13-1, displays two conserved binding modes: forming C2A/C2A homodimers, or forming a heterodimer with the zinc finger domain of UNC-10/RIM (C2A/RIM). Functional analysis revealed that UNC-13L’s C2A promotes synaptic transmission by regulating a post-priming process. Stimulus-evoked release but not SV priming, was impaired in unc-10 mutants deficient for C2A/RIM heterodimerization, leading to decreased release probability. Disrupting C2A/C2A homodimerization in UNC-13L-rescued animals had no effect on synaptic transmission, but fully restored the evoked release and the release probability of unc-10/RIM mutants deficient for C2A/RIM heterodimerization. Thus, our results support the model that RIM binding C2A releases UNC-13L from an autoinhibitory homodimeric complex to become fusion-competent by functioning as a switch only.

Dioscorea L., the largest genus of the family Dioscoreaceae with over 600 species, is not only an important food but also a medicinal plant. The identification and classification of Dioscorea L. is a rather difficult task. In this study, we sequenced five Dioscorea chloroplast genomes, and analyzed with four other chloroplast genomes of Dioscorea species from GenBank. The Dioscorea chloroplast genomes displayed the typical quadripartite structure of angiosperms, which consisted of a pair of inverted repeats separated by a large single-copy region, and a small single-copy region. The location and distribution of repeat sequences and microsatellites were determined, and the rapidly evolving chloroplast genome regions (trnK-trnQ, trnS-trnG, trnC-petN, trnE-trnT, petG-trnW-trnP, ndhF, trnL-rpl32, and ycf1) were detected. Phylogenetic relationships of Dioscorea inferred from chloroplast genomes obtained high support even in shortest internodes. Thus, chloroplast genome sequences provide potential molecular markers and genomic resources for phylogeny and species identification.

CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species.

Background: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups. Results: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)—characterized as tumors mimicking malignant orbital lymphoma (OL)—responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions—involving both lacrimal glands on CT scans—higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674–1.000, p = 0.005] vs. 0.766 [95% CI: 0.615–0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518–0.997] vs. 0.75 [95% CI: 0.509–0.913]), higher specificity (0.813 [95% CI: 0.544–0.960] vs. 0.778 [95% CI: 0.578–0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

Background Acetylsalicylic acid was renamed aspirin in 1899, and it has been widely used for its multiple biological actions. Because of the diversity of the cellular processes and diseases that aspirin reportedly affects and benefits, uncertainty remains regarding its mechanism in different biological systems. Methods The Drugbank and STITCH databases were used to find direct protein targets (DPTs) of aspirin. The Mentha database was used to analyze protein–protein interactions (PPIs) to find DPT-associated genes. DAVID was used for the GO and KEGG enrichment analyses. The cBio Cancer Genomics Portal database was used to mine genetic alterations and networks of aspirin-associated genes in cancer. Results Eighteen direct protein targets (DPT) and 961 DPT-associated genes were identified for aspirin. This enrichment analysis resulted in eight identified KEGG pathways that were associated with cancers. Analysis using the cBio portal indicated that aspirin might have effects on multiple tumor suppressors, such as TP53, PTEN, and RB1 and that TP53 might play a central role in aspirin-associated genes. Discussion The results not only suggest that aspirin might have anti-tumor actions against multiple cancers but could also provide new directions for further research on aspirin using a bioinformatics analysis approach.

East Asia emits more greenhouse gases into the atmosphere than any other region, yet little is known about attitudes towards climate change in this region. A cross-sectional survey investigating climate change knowledge, concern and behavior change was administered to 1118 university students at nine universities across Taiwan in June 2016. Knowledge was assessed with a 15-item quiz while concern and behavioral change were self-reported on 5-point Likert scales. The relationship of these three variables with various socio-demographic variables was investigated through Kruskal-Wallis tests and ordinal logistic regressions. Knowledge was homogeneous by region but differed sharply by socioeconomic position. Concern appears high by international standards, with 65% reporting being "somewhat concerned" and 28% being "very concerned," while climate change denial was negligible. Students expressing greater concern were more likely to be from eastern and southern Taiwan, regions more vulnerable to extreme weather events. However, these high concern levels did not translate into action, as only 38% of respondents reported "some" and 11% reported "very much" behavioral change in response to climate change. Higher levels of behavioral change were reported by students expressing greater concern and students with lower levels of climate change knowledge. In contrast with studies of Western societies, our findings suggest an East Asian model in which the conflict between economic growth and the environment is playing out in different ways, such that the crucial need is for policy leadership and not more education.

The bird cherry-oat aphid, Rhopalosiphum padi (L.), is a major insect pest of cereal crops in many countries. Imidacloprid has been widely used for controlling piercing-sucking insect pests worldwide, but its sublethal effects on R. padi have not been well addressed. In this study, we investigated the sublethal effects of imidacloprid on biological parameters and five enzyme activities of R. padi. The LC10, LC20, and LC25 of imidacloprid to adult aphids were 0.0053, 0.0329 and 0.0659 mg L-1, respectively. These concentrations significantly decreased pre-adult survival rate, but prolonged the development duration of 1st instar nymphs, pre-oviposition period, and adult longevity. Adult oviposition period was also extended by LC20. The intrinsic rate of increase (r), net reproductive rate (R0), and finite rate (λ) decreased at all three concentrations, whereas mean generation time (T) increased. Moreover, LC20 and LC25 significantly inhibited superoxide dismutase (SOD) activity, but increased catalase (CAT) activity. Acetylcholinesterase (AChE) activity also increased at LC20. However, cytochrome P450 enzyme and peroxidase (POD) activity did not differ between imidacloprid treatments and the control. In conclusion, the imidacloprid concentrations tested here have negative impacts on the performance of R. padi by reducing its nymphal survival, extending the development duration of some stages, decreasing the rate of population growth, and altering enzyme activities.

Early-onset cataracts (EOC) are associated with an increased inflammatory response; therefore, a potential risk of other inflammatory diseases, like peptic ulcer, may be related. This study investigated the risk of peptic ulcer after being diagnosed with EOC. Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. Study subjects comprised patients with EOC (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9- CM] codes 366.00, 366.01, 366.02, 366.03, 366.04, 366.09, 366.17 and 366.18), aged 20-55 years and newly diagnosed between 2000 and 2010 (n = 1910), and a comparison cohort without the disease (n = 7515). Both cohorts were followed up until 2010 to estimate the incidences of peptic ulcer. We used the Poisson regression model to compare incidence rate ratios and the 95% confidence interval (CI). Cox proportional hazards regression was used to assess the hazard ratio (HR) of peptic ulcer associated with EOC. The overall incidence rate of peptic ulcer was higher in the EOC cohort than in the comparison cohort (10.3 vs 7.68 per 1000 person-years) with an adjusted HR of 1.33 (95% CI = 1.05, 1.69). The present study suggests that patients with EOC are at an increased risk of being diagnosed with peptic ulcer in subsequent years.