Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by ...National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Photonic transistor memory has received increasing attention as next-generation optoelectronic devices for light fidelity (Li-Fi) application due to the attractive advantages of ultra-speed, high ...security, and low power consumption. However, most transistor-type photonic memories developed to date still rely on electrical bias for operation, imposing certain limits on data transmission efficiency and energy consumption. In this study, the dual manipulation of “photo-writing” and “photo-erasing” of a novel photonic transistor memory is successfully realized by cleverly utilizing the complementary light absorption between the photoactive material, n-type BPE-PTCDI, in the active channel and the hybrid floating gate, CH3NH3PbBr3/poly(2-vinylpyridine). The fabricated device not only can be operated under the full spectrum but also shows stable switching cycles of photo-writing (PW)–reading (R)–photo-erasing (PE)–reading (R) (PW–R–PE–R) with a high memory ratio of ∼104, and the memory characteristics possess a stable long-term retention of >104 s. Notably, photo-erasing only requires 1 s light illumination. Due to the fully optical functionality, the rigid gate electrode is removed and a novel two-terminal flexible photonic memory is fabricated. The device not only exhibits stable electrical performance after 1000 bending cycles but also manifests a multilevel functional behavior, demonstrating a promising potential for the future development of photoactive electronic devices.
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IJS, KILJ, NUK, PNG, UL, UM
Very few studies have been conducted to assess the potential preventive role of vaccines, particularly mRNA vaccines, in the improvement of survival among moderate and severe hospitalized patients ...with COVID-19. After community-acquired outbreaks of the Omicron variant from 18 March until 31 May 2022, occurred in Taiwan, this retrospective cohort of 4090 moderate and 1378 severe patients admitted to hospital was classified according to whether they were administered an mRNA-based vaccine, and followed up to ascertain rates of death in both the vaccinated (≥2 doses) and unvaccinated (no or 1 dose) groups. The age-adjusted hazard ratio (aHR) of less than 1 was used to assess the preventive role of mRNA vaccines in reducing deaths among moderate and severe Omicron-infected patients. Survival was statistically significantly better for the ≥2 dose jab group (aHR, 0.75, 95% confidence interval CI, 0.60 to 0.94) and even higher among those who had received a booster jab (aHR, 0.71; 95% CI, 0.55 to 0.91) compared with the unvaccinated group among moderate patients, but not among severe patients. In conclusion, unveiling the role of mRNA vaccines in preventing moderate but not severe COVID-19 patients from death provides new insights into how mRNA vaccines play a role in the pathway leading to a severe outcome due to Omicron COVID-19.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Finding a model-based optimal design that can optimally discriminate among a class of plausible models is a difficult task because the design criterion is non-differentiable and requires 2 or more ...layers of nested optimization. We propose hybrid algorithms based on particle swarm optimization (PSO) to solve such optimization problems, including cases when the optimal design is singular, the mean response of some models are not fully specified and problems that involve 4 layers of nested optimization. Using several classical examples, we show that the proposed PSO-based algorithms are not models or criteria specific, and with a few repeated runs, can produce either an optimal design or a highly efficient design. They are also generally faster than the current algorithms, which are generally slow and work for only specific models or discriminating criteria. As an application, we apply our techniques to find optimal discriminating designs for a dose-response study in toxicology with 5 possible models and compare their performances with traditional and a recently proposed algorithm. In the supplementary material, we provide a R package to generate different types of discriminating designs and evaluate efficiencies of competing designs so that the user can implement an informed design.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was ...first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long‐term urate‐lowering treatment. Urate‐lowering drugs should be used during the inter‐critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate‐lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Explaining colour variation among animals at broad geographic scales remains challenging. Here we demonstrate how deep learning-a form of artificial intelligence-can reveal subtle but robust patterns ...of colour feature variation along an ecological gradient, as well as help identify the underlying mechanisms generating this biogeographic pattern. Using over 20,000 images with precise GPS locality information belonging to nearly 2,000 moth species from Taiwan, our deep learning model generates a 2048-dimension feature vector that accurately predicts each species' mean elevation based on colour and shape features. Using this multidimensional feature vector, we find that within-assemblage image feature variation is smaller in high elevation assemblages. Structural equation modeling suggests that this reduced image feature diversity is likely the result of colder environments selecting for darker colouration, which limits the colour diversity of assemblages at high elevations. Ultimately, with the help of deep learning, we will be able to explore the endless forms of natural morphological variation at unpreceded depths.
This works reveals that copolymers containing sulfobetaine methacrylate (SBMA) units as antifouling agents fail at providing poly(vinylidene fluoride) (PVDF) membranes with antifouling properties ...after a steam sterilization procedure. Contrarywise, copolymers containing sulfobetaine methacrylamide (SBAA) units are unaffected by the steam sterilization. In other words, the antifouling properties of the coated membranes are comparable before or after steam sterilization. In this study, two copolymers containing styrene segments, ethylene glycol methacrylate segments and either SBMA or SBAA (PS-r-PEGMA-r-PSBMA and PS-r-PEGMA-r-PSBAA) were synthesized and coated on commercial hydrophobic membranes. After characterizing the membranes’ physicochemical properties and verifying that the sterilization had little effect on the coating stability, it was demonstrated that membranes coated with PS-r-PEGMA-r-PSBAA had comparable hydrophilic properties and antibiofouling properties (tested using Escherichia coli, fibrinogen, whole blood) before and after sterilization, while membranes coated with PS-r-PEGMA-r-PSBMA failed. Liquid chromatography and mass spectrometry (LCMS) analysis revealed that steam sterilization of SBMA monomers (279 g/mol) arose in the ester bond cleavage. Species of Mw 211 g/mol could be detected, alongside original SBMA species at 279 g/mol from the MS spectrum of the monomer. On the other hand, the structure of SBAA remained intact after the process. A similar observation was made with copolymers: while cleavage of PS-r-PEGMA-r-PSBMA to numerous fragments occurred, the analysis of PS-r-PEGMA-r-PSBAA did not provide evidence of the copolymer fragmentation in the detection range. Therefore, the results of this work provide solid evidence that it is preferable to use SBAA-derivatives to improve the fouling resistance of membranes if steam sterilization is needed (as in biomedical industry), rather than common SBMA.
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•Zwitterionic copolymers are synthesized and coated on PVDF membranes•Steam sterilized sulfobetaine methacrylate-coated membranes lost their antifouling properties•Steam sterilized sulfobetaine acrylamide-coated membranes retained their antifouling properties•Steam sterilization cleaves sulfobetaine methacrylate derivatives•Steam sterilization does not affect sulfobetaine acrylamide derivatives
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The roles of ambient fine particulate matter (PM2.5) in the prevention of colorectal cancer (CRC) have been scarcely highlighted as there is short of empirical evidence regarding the influences of ...PM2.5 on multistep carcinogenic processes of CRC. A retrospective cohort design with multistate outcomes was envisaged by linking monthly average PM2.5 concentrations at 22 city/county level with large-scale cohorts of cancer-screened population to study the influences of PM2.5 on short-term inflammatory process and multistep carcinogenic processes of CRC. Our study included a nationwide CRC screening cohort of 4,628,995 aged 50–69 years who attended first screen between 2004 and 2009 and continued periodical screens until 2016. We aimed to illustrate the carcinogenesis of PM2.5 related to CRC by applying both hierarchical logistical and multistate Markov regression models to estimate the effects of air pollution on fecal immunochemical test (FIT) positive (a proxy of inflammatory marker) and pre-clinical and clinical states of CRC in the nationwide cohort. We found a significant association of high PM2.5 exposure and FIT-positive by an increased risk of 11% 95% confidence interval (CI), 10–12. PM2.5 enhanced the risk of being preclinical state by 14% (95% CI, 10–18) and that of subsequent progression from pre-clinical to clinical state by 21% (95% CI, 14–28). Furthermore, the elevated risks for CRC carcinogenesis were significantly higher for people living in high PM2.5 pollution areas in terms of yearly averages and the number days above 35 µg/m3 than those living in low PM2.5 pollution areas. We concluded that both short-term and long-term PM2.5 exposure were associated with multistep progression of CRC, which were useful to design precision primary and secondary prevention strategies of CRC for people who are exposed to high PM2.5 pollution.
Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a ...genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10
to 3.44 × 10
) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Large gatherings of people on cruise ships and warships are often at high risk of COVID-19 infections. To assess the transmissibility of SARS-CoV-2 on warships and cruise ships and to quantify the ...effectiveness of the containment measures, the transmission coefficient (β), basic reproductive number (R0), and time to deploy containment measures were estimated by the Bayesian Susceptible-Exposed-Infected-Recovered model. A meta-analysis was conducted to predict vaccine protection with or without non-pharmaceutical interventions (NPIs). The analysis showed that implementing NPIs during voyages could reduce the transmission coefficients of SARS-CoV-2 by 50%. Two weeks into the voyage of a cruise that begins with 1 infected passenger out of a total of 3,711 passengers, we estimate there would be 45 (95% CI:25-71), 33 (95% CI:20-52), 18 (95% CI:11-26), 9 (95% CI:6-12), 4 (95% CI:3-5), and 2 (95% CI:2-2) final cases under 0%, 10%, 30%, 50%, 70%, and 90% vaccine protection, respectively, without NPIs. The timeliness of strict NPIs along with implementing strict quarantine and isolation measures is imperative to contain COVID-19 cases in cruise ships. The spread of COVID-19 on ships was predicted to be limited in scenarios corresponding to at least 70% protection from prior vaccination, across all passengers and crew.
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