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Goal-directed aiming relies on the ability to control attention and visuomotor movements while preparing for motor execution. Research in precision sports has investigated cortical oscillations for supporting expert performance. However, the results may be influenced by adaptive and strategic behaviors after intensive training. Whether and at what time points distinctive oscillations support goal-directed aiming without such training remains elusive. In this electroencephalographic (EEG) study, we investigated how the theta, alpha and beta oscillations change to support accurate aiming before novices took an action. We first conducted a model-based analysis to examine the correlation of cortical oscillations with accurate shooting on a trial-by-trial basis in a within-individual manner. The results showed that alpha and beta oscillations at different time points during the aiming period were better predictors of aiming accuracy. We then compared the oscillatory power for good versus poor performance. The results showed decreases in the alpha and beta power across distributed cortical areas and an increase in the frontal theta power successively before shot release. Moreover, greater intertrial phase coherence was observed for good performance than for poor performance in posterior alpha activity and anterior beta activity during the aiming period. In conclusion, these results advance our understanding of the temporal dynamics of theta, alpha and beta oscillations in orchestrating goal setting, motor preparation and focused attention to monitoring both external and internal states for accurate aiming. Among the three, alpha and beta oscillations are critical for predicting aiming performance and theta oscillations reflect effortful cognitive control.

At present, no definitive treatment for articular cartilage defects has been perfected. Most of the previous treatments involved multiple drilling and microfracture over defect sites with repair-related substances, which poses a limited therapeutic effect. End-stage therapy includes artificial knee joint replacement. In this study, we prepared a novel decellularized natural cartilage scaffold from porcine articular cartilage by supercritical CO2 extraction technology and three-dimensional (3D) composites made using decellularized porcine cartilage graft (dPCG) as scaffolds, platelet-rich plasma (PRP), thrombin as signals and chondrocytes as cells for the treatment of articular cartilage defects. In this study, in vitro and in vivo cartilage regeneration and the expression of chondrogenic markers were examined. Decellularized cartilage graft (dPCG) was evaluated for the extent of cell and DNA removal. Residual cartilage ECM structure was confirmed to be type II collagen by SDS PAGE and immunostaining. The new 3D composite with dPCG (100 mg and 2 × 106 chondrocytes) scaffold promotes chondrogenic marker expression in vitro. We found that the in vivo 3D composite implanted cartilage defect showed significant regeneration relative to the blank and control implant. Immunohistochemical staining showed increase of expression including Collagen type II and aggrecan in 3D composite both in vitro and in vivo studies. In this study, the bioengineered 3D composite by combining dPCG scaffold, chondrocytes, and PRP facilitated the chondrogenic marker expression in both in vitro and in vivo models with accelerated cartilage regeneration. This might serve the purpose of clinical treatment of large focal articular cartilage defects in humans in the near future.

The main challenge in ferroelectric (FE) random access memory (FRAM) scaling is to maintain a high polarization density on the vertical sidewall of 3-D FE capacitors. Two simple and effective methods—stress engineering and optimized interface orientation—are proposed to facilitate the preferential transition from the tetragonal to the orthorhombic phase for ferroelectricity. Four FE phase-progressive experiments were conducted for 2-D/3-D FRAMs with external stress sources and an interfacial layer (IL). Both 2-D and 3-D FRAMs show the wake-up free feature with the presence of both the external stressor and the optimized IL. To extract the sidewall polarization of 3-D FRAM, a set of testkeys was designed and studied. The 3-D FRAM shows an initial sidewall with good reliability and durability with ${P} _{r} = {18}\,\,\mu \text{C}$ /cm2 and endurance of up to 109 cycles. Furthermore, the retention test with the read mode of ${P} _{\text {0,switch}}$ and ${P} _{\text {1,switch}}$ at 85 °C was investigated, and the imprint effect was proved to be the main cause of retention loss.

AIM The aim of this study was to investigate the associations between candidate gene variants and domains of neuropsychiatric symptoms (NPS) and the changes in these associations over a 1-year period. METHODS Seven hundred and ninety-three Taiwanese participants (47.8% female) with Alzheimer's disease (AD) were enrolled. Genes associated with a risk of developing AD were selected as candidate genes. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), and the NPI-Q total score and sub-scores for the Psychosis, Mood, and Frontal Syndrome domains were calculated. RESULTS Patients with AD and the APOE e4 allele exhibited more obvious symptoms of psychosis. Mood symptoms were associated with CD33 rs3865444 and EPHA1 rs11767557, and frontal symptoms were associated with SORL1 rs3824968. A 1-year Time × Alleles interaction effect of CD33 rs3865444 on mood symptoms was discerned. CONCLUSION Risk genes of AD, which are also associated with NPS, are APOE e4 for psychosis, CD33 and EPHA1 for mood symptoms, and SORL1 for frontal symptoms. The association between CD33 and mood symptoms is dynamic and could change over 1 year; however, the results should be interpreted with caution because corrections for multiple comparisons were not performed.

Background Pseudomonas aeruginosa and nontyphoidal Salmonella (NTS) species may cause enteric illness with sepsis in infancy. The clinical predictors distinguishing the two pathogens have not been comprehensively evaluated in this population in Taiwan. Methods A retrospective matched case–control study was conducted in a teaching hospital in southern Taiwan from January 1, 2003 to January 30, 2019. The patients with community-acquired P. aeruginosa sepsis were matched at a ratio of 1:2 by age and gender with controls (who developed NTS sepsis). Results A total of 21 infants with community-acquired P. aeruginosa sepsis were identified; of these, 12 (57.1%) were male, and the mean ± standard deviation of age was 6.95 ± 2.47 months. Two independent predictors indicative of P. aeruginosa sepsis, as identified by multivariate analysis using conditional logistic regression, were hemoglobin level (Hb) (matched odds ratio [mOR], 0.155; 95% confidence interval [CI], 0.027–0.900; p = 0.038) and platelet count (mOR, 0.988, 95% CI, 0.976–1.000; p = 0.049). The areas under the receiver operating characteristic (ROC) curves of Hb and platelet count for P. aeruginosa sepsis prediction were 0.855 and 0.803, respectively. With cut-off values for Hb of 10.7 g/dL and platelet count of 173,000/μL, the predictors had maximal diagnostic accuracy. Conclusion Most patients with P. aeruginosa sepsis are less than one year old. A lower hemoglobin level and a lower platelet count are significant predictors of P. aeruginosa sepsis. These findings should help to reshape the policy of empirical antibiotics in infants with sepsis.

Purpose This large population-based study is the first to analyze the association between coronary artery disease (CAD) and osteoporosis (OP) from the National Health Insurance Research Database (NHIRD) in Taiwan to determine if CAD is associated with OP. Methods Data from NHIRD, a national, population-based, retrospective, matched cohort study of 23 million patients, were collected to recruit two matched cohorts: with (n = 192,367) and without (n = 192,367) CAD. The Cox model was used to compare the incidence rate ratio and crude hazard ratio (HR) between the two cohorts for osteoporotic fracture and OP. Results The CAD cohort had a significantly increased risk for vertebral compression fracture, with an adjusted HR of 1.74 (95% CI, 1.60–1.89). The cumulative incidence of OP was also statistically higher in the cohort versus without CAD (11.6% vs. 5.6%; p ≤ 0.0001, log-rank) during the 10-year follow-up period. The Cox model showed a 2.04-fold increase in the incidence of OP in the CAD cohort, with an adjusted HR of 2.04 (95% confidence interval [CI], 1.99–2.08). Conclusions A positive association exists between CAD and development of subsequent osteoporotic fracture and OP. Patients with CAD have a significantly increased risk of developing vertebral compression fracture and a higher incident rate ratio of OP. Trial registration IRB approval number: No. C108094 on February 19, 2020.

Search volumes from Google Trends over clear-defined temporal and spatial scales were reported beneficial in predicting influenza or disease outbreak. Recent studies showed Wiener Model shares merits of interpretability, implementation, and adaptation to nonlinear fluctuation in terms of real-time decoding. Previous work reported Google Trends effectively predicts death-related trends for the continent economy, yet whether it applies to the island economy is unclear. To this end, a framework of the mortality-related model for a developed island economy Taiwan was built based on potential death causes from Google Trends, aiming to provide new insights into death-related online search behavior at a population level. Our results showed estimated trends based on the Wiener model significantly correlated to actual trends, outperformed those with multiple linear regression and seasonal autoregressive integrated moving average. Meanwhile, apart from that involved all possible features, two other sets of feature selecting strategies were proposed to optimize pre-trained models, either by weights or waveform periodicity of features, resulting in estimated death-related dynamics along with spectrums of risk factors. In general, high-weight features were beneficial to both “die” and “death”, whereas features that possessed clear periodic patterns contributed more to “death”. Of note, normalization before modeling improved decoding performances.

In this study, we developed a simple and economical method for the green synthesis of Cu

The neurotransmitter phenylethylamine (PEA) is highly susceptible to oxidation to produce phenylacetic acid (PA). The fact that PEA and PA are both metabolites of phenylalanine (Phe) in humans makes them important indicators in the diagnosis of phenylketonuria. In this work, three-color whole-cell biosensors were developed to simultaneously detect these analytes (Phe, PEA, and PA). The tyrosine-responsive promoter was used to control the production of green fluorescent protein signals in response to Phe levels. The FeaR regulon was first used to indicate the presence of PEA, whereas the Paa regulon was used for the detection of PA. The combination of three sensor strains together made it possible to semiquantify the three analytes according to unique color outputs without cross-interference. We sought to optimize various modular components (ribosomal binding sites and fluorescent proteins) to ensure the rapid generation of fluorescent signals. Finally, the biosensors were implemented within a microchannel device to reduce sample consumption in point-of-care assays.

BackgroundAlthough carotid sonographic features have been used as predictors of recurrent stroke, few large-scale studies have explored the use of machine learning analysis of carotid sonographic features for the prediction of recurrent stroke.MethodsWe retrospectively collected electronic medical records of enrolled patients from the data warehouse of China Medical University Hospital, a tertiary medical center in central Taiwan, from January 2012 to November 2018. We included patients who underwent a documented carotid ultrasound within 30 days of experiencing an acute first stroke during the study period. We classified these participants into two groups: those with non-recurrent stroke (those who has not been diagnosed with acute stroke again during the study period) and those with recurrent stoke (those who has been diagnosed with acute stroke during the study period). A total of 1,235 carotid sonographic parameters were analyzed. Data on the patients' demographic characteristics and comorbidities were also collected. Python 3.7 was used as the programming language, and the scikit-learn toolkit was used to complete the derivation and verification of the machine learning methods.ResultsIn total, 2,411 patients were enrolled in this study, of whom 1,896 and 515 had non-recurrent and recurrent stroke, respectively. After extraction, 43 features of carotid sonography (36 carotid sonographic parameters and seven transcranial color Doppler sonographic parameter) were analyzed. For predicting recurrent stroke, CatBoost achieved the highest area under the curve (0.844, CIs 95% 0.824–0.868), followed by the Light Gradient Boosting Machine (0.832, CIs 95% 0.813–0.851), random forest (0.819, CIs 95% 0.802–0.846), support-vector machine (0.759, CIs 95% 0.739–0.781), logistic regression (0.781, CIs 95% 0.764–0.800), and decision tree (0.735, CIs 95% 0.717–0.755) models.ConclusionWhen using the CatBoost model, the top three features for predicting recurrent stroke were determined to be the use of anticoagulation medications, the use of NSAID medications, and the resistive index of the left subclavian artery. The CatBoost model demonstrated efficiency and achieved optimal performance in the predictive classification of non-recurrent and recurrent stroke.

PurposeChimeric antibody Miltuximab®, a human IgG1 engineered from the parent antibody MIL-38, is in clinical development for solid tumour therapy. Miltuximab® targets glypican-1 (GPC-1), a cell surface protein involved in tumour growth, which is overexpressed in solid tumours, including prostate cancer (PCa). This study investigated the potential of89Zr-labelled Miltuximab® as an imaging agent, and177Lu-labelled Miltuximab® as a targeted beta therapy, in a mouse xenograft model of human prostate cancer.MethodsMale BALB/c nude mice were inoculated subcutaneously with GPC-1-positive DU-145 PCa cells. In imaging and biodistribution studies, mice bearing palpable tumours received (a) 2.62 MBq [89Zr]Zr-DFO-Miltuximab® followed by PET-CT imaging, or (b) 6 MBq [177Lu]Lu-DOTA-Miltuximab® by Cerenkov imaging, and ex vivo assessment of biodistribution. In an initial tumour efficacy study, mice bearing DU-145 tumours were administered intravenously with 6 MBq [177Lu]Lu-DOTA-Miltuximab® or control DOTA-Miltuximab® then euthanised after 27 days. In a subsequent survival efficacy study, tumour-bearing mice were given 3 or 10 MBq of [177Lu]Lu-DOTA-Miltuximab®, or control, and followed up to 120 days.ResultsAntibody accumulation in DU-145 xenografts was detected by PET-CT imaging using [89Zr]Zr-DFO-Miltuximab® and confirmed by Cerenkov luminescence imaging post injection of [177Lu]Lu-DOTA-Miltuximab®. Antibody accumulation was higher (% IA/g) in tumours than other organs across multiple time points. A single injection with 6 MBq of [177Lu]Lu-DOTA-Miltuximab® significantly inhibited tumour growth as compared with DOTA-Miltuximab® (control). In the survival study, mice treated with 10 MBq [177Lu]Lu-DOTA-Miltuximab® had significantly prolonged survival (mean 85 days) versus control (45 days), an effect associated with increased cancer cell apoptosis. Tissue histopathology assessment showed no abnormalities associated with [177Lu]Lu-DOTA-Miltuximab®, in line with other observations of tolerability, including body weight stability.ConclusionThese findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([89Zr]Zr-DFO-Miltuximab®) and a beta therapy ([177Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours.

Heavy rainfall and strong wind are the two main sources of disasters that are caused by tropical cyclones (TCs), and typhoons with different characteristics may induce different agricultural losses. Traditionally, the classification of typhoon intensity has not considered the amount of rainfall. Here, we propose a novel approach to calculate the typhoon type index (TTI). A positive TTI represents a “wind type” typhoon, where the overall damage in a certain area from TCs is dominated by strong wind. On the other hand, a negative TTI represents a “rain type” typhoon, where the overall damage in a certain area from TCs is dominated by heavy rainfall. From the TTI, the vulnerability of crop losses from different types of typhoons can be compared and explored. For example, Typhoon Kalmaegi (2008) was classified as a rain-type typhoon (TTI = −1.22). The most affected crops were oriental melons and leafy vegetables. On the contrary, Typhoon Soudelor (2015) was classified as a significant wind-type typhoon in most of Taiwan (TTI = 1.83), and the damaged crops were mainly bananas, bamboo shoots, pomelos, and other crops that are easily blown off by strong winds. Through the method that is proposed in this study, we can understand the characteristics of each typhoon that deviate from the general situation and explore the damages that are mainly caused by strong winds or heavy rainfall at different locations. This approach can provide very useful information that is important for the disaster analysis of different agricultural products.

In this study, we developed a simple and economical method for the green synthesis of Cu2+ sensors based on betaxanthin pigments. Aminoisophthalic acid–betaxanthin was synthesized by coupling 2-ami...

Background The risk of tuberculosis (TB) in patients with impaired kidney function remains unclear by different stages of renal function impairment. Methods We retrospectively recruited all patients with kidney function in a tertiary-care referral center from January 2008 to December 2013 and followed them till December 2016. We defined the primary outcome as active TB development and analyzed the impact of kidney function impairment. Results During the study period, a total of 289,579 patients were enrolled for analysis, and of them, 1012 patients had active TB events in an average of 4.13 years of follow-up. According to kidney function impairment, the incidence rate of TB was similar in patients with no chronic kidney disease (CKD) or stage 1 and stage 2, and it increased apparently at stage 3a (167.68 per 100,000 person-years) to stage 3b, stage 4 and stage 5 (229.25, 304.95 and 349.29 per 100,000 person-years, respectively). In a Cox proportional hazard regression model, the dose response of TB risk among different stages of kidney function impairment increased significantly from CKD stage 3a to stage 5. Patients with long-term dialysis had a hazard ratio of 2.041 (1.092–3.815, p = 0.0254), which is similar to that of stage 4 CKD but lower than that of stage 5. Conclusion In patients with impaired kidney function, the risk of TB increases from CKD stage 3, and in stage 5, the risk is even higher than that of those receiving dialysis. Further strategies of TB control need to consider this high-risk group.

Context Evidence has shown that essential nutrients are highly correlated with the occurrence of esophageal cancer (EC). However, findings from observational studies on the associations between dietary carbohydrate, salt consumption, and the risk of EC remain controversial. Objective The aim of this study was to conduct a systematic review and meta-analysis to confirm the associations of dietary carbohydrate and salt consumption with EC risk. Data Source Various electronic databases (PubMed, MEDLINE, Embase, Google Scholar, Cochrane Library, Chinese Electronic Periodical Services, and China Knowledge Resource Integrated) were searched up until January 31, 2019. Data Extraction Data related to patient characteristics and study characteristics were extracted by 2 independent reviewers. The risk ratio reported as relative risk (RR) or odds ratio (OR) was extracted, and random-effects models were performed to estimate the summary risk ratio. Results In total, 26 studies were included in this analysis, of which 12 studies, including 11 case-control studies and 1 cohort study, examined dietary carbohydrates, and 18 studies, including 16 case-control studies and 2 cohort studies, examined dietary salt. The pooled OR showed that dietary carbohydrate intake was inversely related to EC risk (OR = 0.62; 95% confidence interval [CI], 0.50–0.77), but positive correlations between dietary salt intake and the risk of EC were supported by the recruited case-control studies (OR = 1.97; 95% CI, 1.50–2.61) and cohort studies (RR = 1.04; 95% CI, 1.00–1.08). Conclusions Salt is an essential nutrient for body functions and biochemical processes. Providing health education and management regarding proper use of salt in daily foods and labeling the amount of sodium in manufactured products to reduce the risk of developing EC should be more appropriately performed in the general population.

The aromatic amino acid tyrosine is an essential precursor for the synthesis of catecholamines, including l-DOPA, tyramine, and dopamine. A number of metabolic disorders have been linked to abnormal tyrosine levels in biological fluids. In this study, we developed an enzyme cascade-triggered colorimetric reaction for the detection of tyrosine, based on the formation of yellow pigment (betalamic acid) and red fluorometric betaxanthin. Tyrosinase converts tyrosine to l-DOPA, and DOPA-dioxygenase catalyzes oxidative cleavage of l-DOPA into betalamic acid. Response is linear for tyrosine from 5 to 100 μM, and the detection limit (LOD) is 2.74 μM. The enzyme cascade reaction was applied to monitor tyrosinase activity and tyrosinase inhibition assays. Lastly, the performance of the proposed biosensor proved successful in the analysis of urine samples without the need for pre-treatment.

Background Alpha-asymmetry neurofeedback (ALAY) was applied to patients with major depressive disorder (MDD) based on the theory of frontal alpha asymmetry. Neurophysiological studies have found a higher high-beta activity of electroencephalography (EEG) at the posterior cortex among patients with comorbid MDD and anxiety symptoms. The present study examined the effects of ALAY and high-beta down-training (Beta) neurofeedback in symptoms of depression and anxiety and EEG parameters. Method Eighty-seven patients with comorbid MDD and anxiety symptoms were allocated to the ALAY, Beta, or control groups. Both neurofeedback groups received ten-session neurofeedback. All participants completed the Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), and five minutes resting EEG recording at pre-test and post-test. EEG raw signals were transformed into an A1 score [log (F4 alpha) - log (F3 alpha)], P3 and P4 high-beta power. Results BDI-II and BAI scores decreased at post-test in both ALAY and Beta groups, but no significant difference between the two groups. No significant interaction effect in A1 score at pre-test and post-test between the ALAY, Beta, and control groups. The P3 high-beta was significantly decreased in the Beta group, an increase in the control group, and no change in the ALAY group at post-test compared to the pre-test. Conclusions Both neurofeedback groups decreased symptoms of depression and anxiety. The Beta group was more effective in decreasing high-beta power at the parietal cortex compared to other groups. This non-invasive psychological intervention can be used in the future for patients with comorbid MDD and anxiety symptoms.

In this study, we report on a bi-metal organic framework, MOF-919 (Fe-Cu), capable of bifunctional-enzyme mimicking activity with oxidase- and peroxidase-like activities. The catalytic activities were examined by using

Background: Coronaviruses caused three pandemics and impact public health globally in the 21st century. However, limited data were for the evaluation of the trend of coronavirus researches. We aimed to analyze quantitatively, qualitatively, and visually evaluate global scientific publications on coronavirus by using bibliometric analysis. Methods: Coronavirus-related research from 1990-2019 was retrieved from the Web of Science Core Collection database (WoS). Microsoft Excel and VOS viewer software were used to assess the characteristics of publications. Results: Overall, 9,553 publications on coronavirus were retrieved on 12 Mar 2020. The United States took a leading position in coronavirus-related research and accounted for more than one-thirds (36.7%) of all publications. The most productive journal in this field was Journal of Virology (1,056, 11.1%), and the most productive institution was University of Hong Kong (394, 4.1%). The main hot topics in coronavirus field were virus infection and protein. Active collaborations between countries were observed. Conclusion: Over the past three decades, coronavirus research has gradually increased due to two global outbreaks. Through this global bibliometric evaluation, some relevant evidence could be provided. Corresponding to the impact of novel coronavirus (COVID-19), a large number of articles can be expected to appear in the next few years, and international cooperation should be strengthened to solve the problem.

Transcription factor-based whole-cell biosensors have recently become promising alternatives to conventional analytical methods due to their advantage of simplicity, cost-effectiveness, and environmental friendliness. In this study, we used genetic engineering to develop a whole-cell biosensor based on the activation of promoters by CupR via interactions with gold ions, leading to the expression of reporter genes that yield output signals. Altering the promoter sequences was shown to significantly improve the performance of the biosensor strain in terms of gold-specificity. The detection sensitivity of our engineered strains was 42-fold higher than that of wild-type strains. The linear range of the purposed sensor was 125-1000 nM with a limit of detection at 46.5 nM. The effectiveness of the sensor strain was verified in wastewater samples.

Summary Calcium influx through plasma membrane calcium release-activated calcium (CRAC) channels, which are formed of hexamers of Orai1, is a potent trigger for many important biological processes, most notably in T cell-mediated immunity. Through a bioinformatics-led cell biological screen, we have identified Orai1 as a substrate for the rhomboid intramembrane protease RHBDL2. We show that RHBDL2 prevents stochastic calcium signaling in unstimulated cells through conformational surveillance and cleavage of inappropriately activated Orai1. A conserved disease-linked proline residue is responsible for RHBDL2's recognizing the active conformation of Orai1, which is required to sharpen switch-like signaling triggered by store-operated calcium entry. Loss of RHBDL2 control of CRAC channel activity causes severe dysregulation of downstream CRAC channel effectors, including transcription factor activation, inflammatory cytokine expression, and T cell activation. We propose that this surveillance function may represent an ancient activity of rhomboid proteases in degrading unwanted signaling proteins.

Materials that have higher fluorescence emission in the solid state than molecules in solution have recently been paid more attention by the scientific community due to their potential applications in various fields. In this work, we newly synthesized benzoxazolyl-imidazole and benzothiazolyl-imidazole conjugates, which show aggregation-induced emission (AIE) features in their solid and aggregate states. It was found that oxygen and sulfur substitutions can dramatically influence the molecular structures and polarities of the dyes, leading to different degrees of the AIE phenomenon. The benzothiazolyl-imidazole molecule has lower polarity compared to that of benzoxazolyl-imidazole; therefore, the dye bearing a benzothiazolyl group shows higher emission intensity and dual emission in aqueous solution. Theoretical calculation results suggest that the benzothiazolyl-imidazole molecules might have electrostatic interactions between sulfur and nitrogen atoms, explaining the experimental observations of lower critical aggregation concentration and photophysical properties both in solution and in the solid state. The theoretical calculations agree with the experimental data, thus demonstrating a potent strategy to gain a deep understanding of the structure-property relationships to design solid-state fluorescent materials.

Background: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis–related complications such as portal hypertension (pHTN). This study compared the outcomes of metastatic breast cancer in patients with imaging-diagnosed pseudocirrhosis with or without pHTN. Methods: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Clinical pHTN was defined based on endoscopic evidence of esophageal or gastric varices. Results: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)–positive and human epidermal growth factor receptor 2 (HER2)–negative breast cancer. In total, 81 (76%) had initial metastases in both hepatic lobes, 91 (86%) had 4 or more liver metastases, and 32 (30%) had pHTN. The median overall survival (OS) was 5 and 13 months in patients with and without pHTN, respectively (p = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative breast cancer was 16, 9, and 2 months, respectively (p = .001). Patients with pHTN generally had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with pHTN had OS exceeding 1 year. In multivariate analysis, pHTN (p = .007) and triple-negative breast cancer (p = .013) were associated with poor OS. Conclusions: For patients with pseudocirrhosis, clinical pHTN was associated with liver cirrhosis–related complications and shorter median OS. A few patients with pHTN had prolonged OS with effective systemic treatment and aggressive supportive care.

We examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods.This retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure.Over a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79-0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87-1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94-1.31) using the MSM approach.Statin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.

Trade-offs between competition ability and invulnerability to predation are important mechanisms explaining how predation promotes bacterial diversity. However, existence of these trade-offs has apparently not been investigated in natural marine bacterial communities. Here, we address this question with growth-based measurements for each marine bacterial taxon by conducting on-board dilution experiments to manipulate predation pressure and using high-throughput sequencing to assess the response of bacterial communities. We determined that bacterial taxa with a higher predation-free growth rate were accompanied with higher predation-caused mortality, supporting existence of competitiveness-invulnerability trade-off. This trade-off was stronger and more consistent under viral lysis than protist grazing. In addition, predation generally flattened out the rank-abundance distribution and increased the evenness and richness of the bacterial community. These findings supported the “Kill-the-Winner” hypothesis. All experiments supported a significant competitiveness-invulnerability trade-off, but there was substantial variation among bacterial communities in response to predation across experiments conducted in various sites and seasons. Therefore, we inferred that the Kill-the-Winner hypothesis is important but likely not the only deterministic mechanism explaining how predation shapes bacterial assemblages in natural marine systems.

Many studies have shown that fine particulate matter can cause health problems. Thus, effectively controlling fine particulate matter concentration is an important issue around the world. The Taiwan Environmental Protection Administration (TWEPA) divides Taiwan into seven air quality zones based on counties and cities for managing air quality and analyzing pollution transmission. However, this artificial division by administrative areas relatively poorly match natural conditions and topographical and geographic factors and hence poorly represent air quality characteristics. This study proposes an air quality sensitive map analysis framework, which uses hierarchical agglomerative clustering with empirical orthogonal function and analysis of variance methods, to provide more detailed, reasonable, and township-level air quality zones incorporating the different spatial-temporal characteristics over the region. The risk concept is introduced to evaluate PM