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Abstract Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA‐DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA‐DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti‐Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti‐La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti‐CCP) antibodies, and DR11 was associated with increased risk of formation of anti‐La antibodies. Oral ulcer was found to be negatively associated with anti‐Ro antibodies and with anti‐ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA‐DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA‐DR8 appeared to be a risk factor. In addition, we found several associations between HLA‐DR genotype, clinical presentation, and autoantibody status among them.

Abstract Background Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. Objective This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. Methods Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. Results Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. Conclusion Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as the standard first-line treatment for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, the impact of comorbidities and treatment toxicities on quality of life (QoL) was seldom investigated. Objective: We aimed to investigate the association of comorbidities, adverse events (AEs), and QoL in treatment-naïve advanced NSCLC patients receiving EGFR-TKI treatments. Methods: This multi-center prospective observational study was conducted to evaluate QoL and AEs at baseline, the 2nd, 4th, 12th, and 24th week. Clinical characteristics, comorbidities, and pre-treatment laboratory data were recorded. QoL was assessed by using the summary score of the EORTC QLQ-C30 and the dermatology life quality index. The impact of comorbidities, neutrophil-to-lymphocyte ratio (NLR), and AEs on QoL was analyzed by generalized estimating equations. Results: A total of 121 patients were enrolled. Diarrhea (p = 0.033), anorexia (p

PURPOSE: This study aimed to explore the safety and efficacy of laser treatment settings of micropulse transscleral cyclophotocoagulation treatment in glaucoma patients and to evaluate the relationship between intraocular pressure (IOP) reduction and different treatment parameters. MATERIALS AND METHODS: A total of 74 eyes in 64 glaucoma patients with IOP over 21 mmHg or under 20 mmHg with visual field progression who underwent micropulse transscleral cyclophotocoagulation treatment were included. Patients were divided into success and failure groups based on criteria of 20% IOP reduction rate. The predictive factors of IOP reduction between success and failure groups and the IOP reduction rates in the different treatment duration groups were evaluated. Predictive factors for IOP reduction were analyzed using univariate and multivariate regression models. Results: Patients in the success group had significantly higher baseline IOP (median: 28.0 vs. 23.0 mmHg; P = 0.016) and longer treatment times (median: 240 vs. 160 s; P = 0.001). Treatment duration range between 200 and 240 s achieved significantly higher intraocular pressure reduction rates (47.8 ± 17.4%) than durations under 140 s (23.1 ± 14.2%). Univariate analysis showed that baseline IOP and treatment duration were significant contributing factors in IOP reduction. Multivariable analysis further demonstrated that treatment duration over 200 s was the significant predictive factor for IOP reduction. Conclusion: Treatment duration settings were the most significant factor of IOP reduction rates in micropulse cyclophotocoagulation. Customized therapy according to the target IOP reduction rate can be applied with different treatment duration settings to achieve optimal outcomes.

Evapotranspiration is the main factor of plant growth, which can be estimated using different methods. Accurate estimation of evaporation and transpiration helps in planning to meet the actual needs of the plant. In general, daily evapotranspiration depends on temperature, climate, soil moisture, plant, growth period, root length, and the texture of the root zone porous media. In this study, the moisture balance of the soil surface is simulated daily and the components of deep percolation, evaporation, irrigation, and transpiration are calculated. The obtained results have been compared with the output of the surface energy balance algorithm for land (SEBAL) algorithm to determine the energy balance on the earth's surface and to estimate evapotranspiration. Normalized objective function (NOF), Nash–Sutcliffe efficiency index, and mean absolute error were incorporated into the problem for evaluating the predicted values. The energy balance of the soil surface and the moisture balance of the root zone each have a different process in estimating the actual evaporation and transpiration, but the correlation between them was acceptable. The interval between the calculated values can be used as input data to determine the irrigation requirement. HIGHLIGHTS Soil moisture balance and plant surface energy balance have been compared to determine evaporation and transpiration.; The use of daily steps in modeling increased the accuracy of calculations.; The correlation between SEBAL and soil moisture balance is acceptable.;

Sustainable planning of water allocation in the agricultural sector requires attention to soil, plant, climate and their limitations. This study was conducted in order to develop a real-time framework for simulating soil–water balance in the root zone, crop growth curve and irrigation planning of rapeseed cultivation in Henan Province, China during a cropping season from March to October 2022. Simulation of production functions with field information calibration at daily time step was developed to accurately estimate the simulation of crop growth and soil water balance. Particle swarm optimization (PSO) algorithm is incorporated as an efficient tool to evaluate the water productivity as objective function in a self-organizing framework. Choosing the appropriate planting date for rapeseed cultivation at the beginning of the growing season was evaluated to increase the use of precipitation for canopy cover growth and thus reduce irrigation water consumption. The results showed that the proposed model increased water productivity by 23% as the objective function, and evaporation from the soil surface decreased by 16%. The maximum difference between the irrigation depth in the optimal and existing strategies was 41 mm in the germination stages until the seed-filling stage, which caused a decrease in final biomass and plant transpiration. HIGHLIGHTS An optimization framework was used to find the sustainable strategy of water distribution in rapeseed cultivation.; A daily time step modeling was developed to estimate the crop growth process.; Improving the planting date increased water productivity and effective use of rainfall.;

Abstract Background Studies comparing the effectiveness of either adjuvant oral uracil‐tegafur (UFT) or intravenous chemotherapy on early‐stage (stage I and II) non‐small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. Methods From January 2011 to December 2017, patients with early‐stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse‐free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. Results A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49–0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61–0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score‐matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48–1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72–1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non‐drinker (HR: 0.66, 95% CI: 0.34–0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42–0.97, p = 0.0341). Conclusions This population‐based study in the real‐world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early‐stage NSCLC patients after surgery.

Background: Among the histologic types of lung cancer, adenocarcinoma is the most common. Moreover, lung adenocarcinoma with neuroendocrine differentiation (LANED) is a rare histologic character. So far, the clinical significance remains unclear. Material and methods: We searched for the patients diagnosed with LANED from the electronic pathology database between January 2000 and June 2020 in a tertiary hospital. The tumor specimens were reviewed by a pathologist to confirm the diagnosis. EGFR mutation, ALK translocation, as well as programmed death ligand 1 (PD-L1) and rearranged during transfection (RET) expression were tested in the specimens of LANED. The clinical data were also collected and analyzed. Results: A total of 10 patients diagnosed with LANED were included. Most were male (80%) and ever smokers (70%). The median age was 71.5 years old. At diagnosis, most had tumors harboring no EGFR mutation (70%), negative ALK translocation (88.9%), and without PD-L1 expression (90%). All specimens tested by immunohistochemical staining for RET expression (n = 9) showed positive results. Among the 10 patients, five underwent operation (stage I, n = 4; stage II, n = 1). The patient with stage II disease had recurrence 11 months later. For patients with advanced stages (stage III, n = 1; stage IV, n = 4), the treatment modalities varied and the overall survival ranged from 11.0 to 46.7 months. Conclusion: LANED might be associated with a high proportion of RET expression, whereas EGFR mutation, ALK alteration, and PD-L1 expression were uncommon. Further large-scale prospective studies on molecular testing profile and clinical significance of LANED are warranted.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Abstract Background The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis. Methods This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021. Results Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0–4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 [95% CI, 36.6–46.0] vs. 26.6 months [95% CI, 9.9–43.3], respectively). Conclusion Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.

Improving agricultural production relies on the decisions and actions of farmers and land managers, highlighting the importance of efficient soil monitoring techniques for better resource management and reduced environmental impacts. Despite considerable advancements in soil sensors, their traditional bulky counterparts cause difficulty in widespread adoption and large-scale deployment. Printed electronics emerge as a promising technology, offering flexibility in device design, cost-effectiveness for mass production, and a compact footprint suitable for versatile deployment platforms. This review overviews how printed sensors are used in monitoring soil parameters through electrochemical sensing mechanisms, enabling direct measurement of nutrients, moisture content, pH value, and others. Notably, printed sensors address scalability and cost concerns in fabrication, making them suitable for deployment across large crop fields. Additionally, seamlessly integrating printed sensors with printed antenna units or traditional integrated circuits can facilitate comprehensive functionality for real-time data collection and communication. This real-time information empowers informed decision-making, optimizes resource management, and enhances crop yield. This review aims to provide a comprehensive overview of recent work related to printed electrochemical soil sensors, ultimately providing insight into future research directions that can enable widespread adoption of precision agriculture technologies.

Abstracts: Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

Culture substrates display profound influence on biological and developmental characteristic of cells cultured in vitro. This study investigates the influence of polyvinyl alcohol (PVA) substrates blended with different concentration of collagen or/and gelatin on the cell adhesion, proliferation, shape, spreading, and differentiation of stem cells. The collagen/gelatin blended PVA substrates were prepared by air drying. During drying, blended collagen or/and gelatin can self-assemble into macro-scale nucleated particles or branched fibrils in the PVA substrates that can be observed under the optical microscope. These collagen/gelatin blended substrates revealed different surface topography, z-average, roughness, surface adhesion and Young’s modulus as examined by the atomic force microscope (AFM). The results of Fourier transform infrared spectroscopy (FTIR) analysis indicated that the absorption of amide I (1,600–1,700 cm−1) and amide II (1,500–1,600 cm−1) groups increased with increasing collagen and gelatin concentration blended and the potential of fibril formation. These collagen or/and gelatin blended PVA substrates showed enhanced NIH-3T3 fibroblast adhesion as comparing with the pure PVA, control tissue culture polystyrene, conventional collagen-coated and gelatin-coated wells. These highly adhesive PVA substrates also exhibit inhibited cell spreading and proliferation. It is also found that the shape of NIH-3T3 fibroblasts can be switched between oval, spindle and flattened shapes depending on the concentration of collagen or/and gelatin blended. For inductive differentiation of stem cells, it is found that number and ration of neural differentiation of rat cerebral cortical neural stem cells increase with the decreasing collagen concentration in the collagen-blended PVA substrates. Moreover, the PVA substrates blended with collagen or collagen and gelatin can efficiently support and conduct human pluripotent stem cells to differentiate into Oil-Red-O- and UCP-1-positive brown-adipocyte-like cells via ectodermal lineage without the addition of mitogenic factors. These results provide a useful and alternative platform for controlling cell behavior in vitro and may be helpful for future application in the field of regenerative medicine and tissue engineering.

The objective of this study was to improve the energy management of an overhead downward flow (ODF)-type data center (DC) using the evaporative cooling method. A computational fluid dynamics (CFD) approach was used to predict the optimal operating condition of an A1-grade DC exhibiting the smallest entropy generation rate of the ODF system. Experiments were performed to validate the predicted airflow speed at the inlet of each server and temperature distributions at the inlet and outlet of each server. Furthermore, three thermal performance metrics, namely rack cooling index (RCI), return temperature index (RTI), and supply heat index (SHI), were used to compare the numerical and experimental results, which were found to be consistent. The measured power usage effectiveness (PUE) reached 1.42, significantly lower than the global average PUE of 1.55 reported in 2022. Moreover, using the CFD method, water mist was added at the air supply port to reduce the temperature of air from 21.63 °C to 18 °C via evaporation and increase relative humidity from 50% to 70%. These results suggest that evaporative cooling has the potential to facilitate the supplied air to provide additional cooling capacity and lower the chiller load to reduce energy consumption in the DC.

In recent years, multilingual question answering has been an emergent research topic and has attracted much attention. Although systems for English and other rich-resource languages that rely on various advanced deep learning-based techniques have been highly developed, most of them in low-resource languages are impractical due to data insufficiency. Accordingly, many studies have attempted to improve the performance of low-resource languages in a zero-shot or few-shot manner based on multilingual bidirectional encoder representations from transformers (mBERT) by transferring knowledge learned from rich-resource languages to low-resource languages. Most methods require either a large amount of unlabeled data or a small set of labeled data for low-resource languages. In Wikipedia, 169 languages have less than 10,000 articles, and 48 languages have less than 1,000 articles. This reason motivates us to conduct a zero-shot multilingual question answering task under a zero-resource scenario. Thus, this study proposes a framework to fine-tune the original mBERT using data from rich-resource languages, and the resulting model can be used for low-resource languages in a zero-shot and zero-resource manner. Compared to several baseline systems, which require millions of unlabeled data for low-resource languages, the performance of our proposed framework is not only highly comparative but is also better for languages used in training.

Abstract Background and Aims Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. Methods We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. Results Eighty‐six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6–4.6). The most frequently reported adverse events were hand‐foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8–17.0) and the median progression‐free survival (PFS) was 4.2 months (95% CI, 3.7–4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP 10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP

Abstract Background The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases. Methods This study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury. Results By opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls. Conclusion This is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.

The rapid development of the petrochemical industry has caused great harm to the environment. Fine suspended particles with a diameter of less than 2.5 microns cause serious health problems when inhaled air of high concentration of PM2.5. Therefore, an estimate of the concentration of PM2.5 is sought. However, it generally requires expensive instruments installed in an air quality monitoring station and a professional to operate them. In addition to the expensive cost, the instruments require a high maintenance fee and are restricted by geographical location. To eliminate the difficulty, this paper presents a low-cost and effective approach to estimate the concentration of PM2.5 using image processing schemes. The proposed approach consists of four stages. First, images with different concentrations of PM2.5 were taken and the related relative humidity (RH) was collected. Second, an automatically selected region of interest (RoI) was used to extract two features from an image, namely high-frequency information and transmittance by an improved dark channel. Third, the two extracted features, together with the RH measurement, were used to build a support vector regression (SVR) model. Fourth, the SVR model was applied to estimate the concentration of PM2.5, whose performance was then evaluated and compared with four simple regression models and a modified reported SVR method. In the given data set, the proposed method outperforms the comparison methods in terms of $R^{2}$ and root mean squared error. The best performance of our method reaches $R^{2}=0.816$ which is generally satisfactory in related applications.

This paper proposes an edge computing-based video coding implementation on an Earth observation satellite (SAT-video coding), which can encode video using limited resources and the power of mini/microsatellites. SAT-video coding proposes a hardware-related quantization (Q) function, hardware reduction of the motion estimation (ME) method, and simplified entropy coding (EC), which reduces the computation complexity. The hardware-related Q reduces hardware resource and power consumption by 72% and 55%, respectively, compared with traditional Q implementation. The hardware reduction of ME reduces resource use compared with regular ME implementation (59% of lookup tables [LUTs] and 79% of Registers). The total number of LUTs used for the simplified EC function is also much lower than other EC hardware implementations. The SAT-video encoder IP uses fewer hardware resources, and the power consumption is estimated at 0.0894 W at a high working frequency (125 MHz). The SAT-video encoding speed is 18.95 frames per second for $2560\times 2560$ video. Therefore, the proposed SAT-video coding is an edge computation suitable for micro/minisatellites. The coding efficiency records the highest compression ratio at 33.8, with a peak signal-to-noise ratio of 34.46 dB. With the important task of designing edge computing based on satellite video encoding, these are adequate values for remote sensing video.

Abstract Background Piwi-interacting RNAs (piRNAs) are the small non-coding RNAs (ncRNAs) that silence genomic transposable elements. And researchers found out that piRNA also regulates various endogenous transcripts. However, there is no systematic understanding of the piRNA binding patterns and how piRNA targets genes. While various prediction methods have been developed for other similar ncRNAs (e.g., miRNAs), piRNA holds distinctive characteristics and requires its own computational model for binding target prediction. Results Recently, transcriptome-wide piRNA binding events in C. elegans were probed by PRG-1 CLASH experiments. Based on the probed piRNA-messenger RNAs (mRNAs) binding pairs, in this research, we devised the first deep learning architecture based on multi-head attention to computationally identify piRNA targeting mRNA sites. In the devised deep network, the given piRNA and mRNA segment sequences are first one-hot encoded and undergo a combined operation of convolution and squeezing-extraction to unravel motif patterns. And we incorporate a novel multi-head attention sub-network to extract the hidden piRNA binding rules that can simulate the biological piRNA target recognition process. Finally, the true piRNA–mRNA binding pairs are identified by a deep fully connected sub-network. Our model obtains a supreme discriminatory power of AUC $$=$$ = 93.3% on an independent test set and successfully extracts the verified binding pattern of a synthetic piRNA. These results demonstrated that the devised model achieves high prediction performance and suggests testable potential biological piRNA binding rules. Conclusions In this research, we developed the first deep learning method to identify piRNA targeting sites on C. elegans mRNAs. And the developed deep learning method is demonstrated to be of high accuracy and can provide biological insights into piRNA–mRNA binding patterns. The piRNA binding target identification network can be downloaded from http://cosbi2.ee.ncku.edu.tw/data_download/piRNA_mRNA_binding .

Objectives: A definitive diagnosis of pulmonary sarcomatoid carcinoma cannot be made with small biopsies. In clinical practice, a diagnosis of advanced non-small-cell lung cancer with spindle cell and/or giant cell carcinoma (NSCLCsg), or possible sarcomatoid carcinoma, is acceptable. Therefore, we aimed to investigate the treatment patterns and outcomes of advanced NSCLCsg. Materials and methods: Between 01 January 2012 and 01 April 2021, patients with pathologically proven advanced NSCLCsg were enrolled. The choice of treatment was based on clinician discretion. Results: In all, 101 patients with advanced NSCLCsg were enrolled. In total, 77 (76.2%) patients received at least one line of systemic therapy; 44 patients (43.1%) had received platinum doublet chemotherapy; 27 (26.7%) patients had been treated with targeted therapies; and 23 patients (22.8%) had been given an immune checkpoint inhibitor (ICI). The median overall survival (OS) was 6.3 months [95% confidence interval (CI): 3.6–9.0 months]. Excluding patients without systemic therapy, patients who had received an ICI had better OS (median: 18.2 months) than those who had not (median 3.8 months, log-rank test p = 0.002). No significant difference in OS was detected between patients who had or had not received platinum doublet chemotherapy (log-rank test p = 0.279), or targeted therapy (log-rank test p = 0.416). Having received any systemic therapy [hazard ratio (HR): 0.33, 95% CI: 0.18–0.61, p

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.

Purpose – While curiosity is a critical factor in motivating human exploratory behaviors across domains, past studies are yet to explore the exploratory curiosity construct in the context of backpacking. This study aims to conceptualize backpackers’ exploratory curiosity and, importantly, developing a scale for the construct. Design/Methodology – A survey questionnaire is first designed on the basis of a literature review and in-depth interviews. Then, two surveys are conducted using sample sizes of 228 and 276. The scale, along with its four factors (i.e., excitement, new destinations, social contact, and new tourism events) and 18 items, was determined as reliable and valid by the implementation of a rigorous instrument development process. Approach – This study identifies the characteristics of backpacker exploratory curiosity, and then generates fundamental constructs with detailed descriptions and explanations for a questionnaire. Subsequently, to understand the characteristics of such curiosity and how they can be applied to explain backpacker behaviors. Findings – This study extended the application of the curiosity concept to the tourism industry, and offered a new perspective, namely, exploratory behaviour individuals display in response to novelty, excitement, and changes in their environment can be used as variables to measure their curiosity level, and then the BECS can be utilized by tourism management organizations to help increase the number of potential clients. Originality of the research – The study contributed to a theoretical enhancement of the current level of knowledge on the existing literature on backpackers’ exploratory behavior and developed a reliable and valid scale for measuring backpacker exploratory curiosity.

Abstract Mixed‐stock analyses using genetic markers have informed fisheries management in cases where strong genetic differentiation occurs among local spawning populations, yet many fisheries are supported by multiple, weakly differentiated stocks. Freshwater fisheries exemplify this problem, with many populations supported by multiple stocks of young evolutionary age and isolated across small spatial scales. Consequently, attempts to conduct genetic mixed‐stock analyses of inland fisheries have often been unsuccessful. Advances in genomic sequencing offer the ability to discriminate among populations with weak population structure, providing the necessary resolution to conduct mixed‐stock assignment among previously indistinguishable stocks. We used genomic data to conduct a mixed‐stock analysis of eastern Lake Erie's commercial and recreational walleye (Sander vitreus) fisheries and estimate the relative harvest of weakly differentiated stocks (pairwise FST

Abstract The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Abstract Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P 50 years old (HR/CI 3.64/2.03–6.54, P

Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P

Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has shown to have smaller skin incision, decreased muscular dissection, and less retraction of the thecal sac, compared to conventional open approach. However, its effects on long term functional outcome and degenerative changes of paraspinal muscles are still obscure. Materials and Methods: We studied 81 patients treated by one team of surgeons at a single institution. In the two level spinal fusion, 18 patients underwent conventional TLIF (C TLIF) and 20 patients underwent MIS TLIF. In three level spinal fusion, 23 patients were treated with C TLIF and 20 patients were treated with MIS TLIF. Clinical outcomes included mean operative times, volume of blood loss, percentage of early ambulation, visual analog scale (VAS), and oswestry disability index (ODI) were analyzed. The change of multifidus muscle was calculated from magnetic resonance imaging (MRI) taken before and 6-month after the operation. Results: Lesser blood loss was noted in the MIS TLIF group compared to the conventional group in two- or three-level circumferential spinal fusion. Early ambulation (within 3 days after operation) was found in the MIS TLIF groups. Analysis of VAS scores at leg area showed no significant differences in improvement between each group at 18 month follow up. The postoperative ODI score was significantly less in the MIS TLIF groups than in the C TLIF groups after 6 month follow up. In three segment spinal fusion, MIS TLIF minimized multifidus muscle atrophy, when compared with C TLIF. Conclusion: MIS TLIF in three level lumbar fusion not only has a better functional recovery but also ameliorates the degenerative change of multifidus muscle.

Background: This study was to explore the clinical factors associated with treatment toxicities of pemetrexed plus platinum in elderly patients with non-small cell lung cancer (NSCLC). Methods: Chemo-naive patients aged ≥ 70 with advanced NSCLC treated with pemetrexed plus platinum were included. Medical records were reviewed and clinical data, including age, gender, smoking status, comorbidities, EGFR mutation status, chemotherapy regimens, previous use of epidermal growth factor receptor-tyrosine kinase inhibitors, treatment-related hematologic, renal, and hepatic toxicities, and treatment responses, were analyzed. Comorbidity conditions were evaluated by using the Simplified Comorbidity Score (SCS) and Charlson Comorbidity Index Score (CCIS). Results: A total of 144 patients were included. In the univariate analysis, patients with SCS >9 (p = 0.006) and cigarette smoking (p = 0.028) were associated with a significantly higher rate of grade 3/4 neutropenia than their counterpart. Carboplatin use was associated with a higher rate of grade 3/4 thrombocytopenia than cisplatin use (p = 0.028). In the multivariate analysis, SCS >9 was associated with a significantly higher risk of anemia of any grade (odds ratio [OR]: 2.72, 95% confidence interval [CI]: 1.09–6.77). Carboplatin use was associated a higher risk of any grade (OR: 4.61, 95% CI: 1.07–19.90) and grade 3/4 thrombocytopenia (OR: 7.37, 95% CI: 1.36–39.92). No clinical factors were found to be associated with hepatic and renal toxicities. Conclusion: High SCS and carboplatin use were associated with hematological toxicities with pemetrexed plus platinum use in elderly patients with NSCLC.

Background/purposes: Infective endocarditis (IE) is an important cause of morbidity and mortality in hemodialysis (HD) patients. Data on the differences in the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE are limited. Methods: Medical records of patients (aged over 20 years) with IE were retrospectively reviewed from January 2008 to June 2017 in a tertiary care center in Northern Taiwan. Those with definite or possible IE were included in the study. The clinical characteristics, microbiological results, echocardiographic findings and outcomes of patients were analyzed. Results: Of the 183 patients with definite or possible IE, 47 had undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson comorbidity index, 8.17 vs. 4.21, p

Infection is a possible cause of rhabdomyolysis. We describe the case of a 63-year-old male with malaise and erythematous papules on the right C5–C7 dermatomes, consistent with herpes zoster. Serum antibody and Tzanck tests of the skin lesion were positive. Increased serum creatine kinase (CK) and myoglobin levels and cola-colored urine indicated the development of rhabdomyolysis. Acute kidney injury was also observed. After excluding other possible predisposing factors, the patient was diagnosed with varicella-zoster virus (VZV)-induced rhabdomyolysis. Extracellular volume with alkalized fluids and topical acyclovir was administered. While CK levels declined to normal by day 13, the renal function was not restored. The skin lesion crusted by day 8 and scaled off gradually by day 13. Our case and literature review highlighted the necessity for systemic antiviral treatment and that poor VZV infection control could lead to irreversible kidney injury. In addition, systemic acyclovir should be administered carefully due to its complication of nephrotoxicity.

Recent advances with large-scale pre-trained language models (e.g., BERT) have brought significant potential to natural language processing. However, the large model size hinders their use in IoT and edge devices. Several studies have utilized task-specific knowledge distillation to compress the pre-trained language models. However, to reduce the number of layers in a large model, a sound strategy for distilling knowledge to a student model with fewer layers than the teacher model is lacking. In this work, we present Layer-wise Adaptive Distillation (LAD), a task-specific distillation framework that can be used to reduce the model size of BERT. We design an iterative aggregation mechanism with multiple gate blocks in LAD to adaptively distill layer-wise internal knowledge from the teacher model to the student model. The proposed method enables an effective knowledge transfer process for a student model, without skipping any teacher layers. The experimental results show that both the six-layer and four-layer LAD student models outperform previous task-specific distillation approaches during GLUE tasks.

ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

Seagrass beds are major blue carbon ecosystems. Climate change-associated factors may change the seagrass community and affect the capacity of carbon sequestration. To explore the possible effects of warming, higher precipitation levels and/or sea level rise on seagrasses, the spatial and seasonal dynamics in shallow seagrass beds comprising the late-successional seagrass Thalassia hemprichii and the early-successional seagrass Halodule uninervis were tracked. The high-resolution mapping of seagrass biomass dynamics showed that T. hemprichii was the dominant species in the study sites year round, as the space occupation by the larger seagrass T. hemprichii was more efficient than that by the smaller seagrass H. uninervis. The space occupation by both species in the low-elevation site was more efficient than in the high-elevation site. In the low-elevation site, while the dominance of the faster growing seagrass H. uninervis was increasing, the dominance of T. hemprichii was decreasing. This suggested that the carbon sequestration capacity of the seagrass beds will decrease, as T. hemprichii was capable of storing more carbon in the sediments. In the high-elevation site, however, the distribution of both species was distinct and showed a clear seasonal succession. The dominance of H. uninervis moved to shallower water in the wet season and then moved back to deeper water in the dry season. Our observations suggested that four possible mechanisms might be involved in the dominance shift in the shallow seagrass beds: (1) the deeper water in the low-elevation site or the higher precipitation levels in the wet season might reduce the drought stress of H. uninervis at low tide and enhance the competition of H. uninervis over T. hemprichii; (2) the growth of H. uninervis might be stimulated more by the flushing of land-based nutrients caused by the higher precipitation rates in the wet season; (3) in the high-elevation site, the faster flow velocity and frequently disturbed sediments in the dry season might constrain the further expansion of H. uninervis to shallower water; (4) the faster flow velocity in the high-elevation site might reduce the impacts of periphyton overgrowth on T. hemprichii and maintain the dominance of T. hemprichii in the community. Our results suggest seagrasses will not necessarily respond to fluctuating environments in the same way in the coming decades.

Background/purpose: HIV-infected patients have a high prevalence of low bone mineral density (BMD), but BMD changes remain unclear. This cross-sectional retrospective observational study aimed to characterize the prevalence and associated factors of low BMD in HIV patients. Methods: Between 1 January 2015 and 31 December 2016, all patients aged 20 years or greater who sought for HIV care were included. BMD was measured by dual-energy X-ray absorptiometry. Multivariable analyses of the association with HIV disease status, treatment and anthropometric parameters were performed. Circulating fibroblast growth factor 23 and intact parathyroid hormone were measured. Results: A total of 137 patients was included; their median age was 39 years old; 97.8% were treated with combination antiretroviral therapy (cART); Body mass index (BMI) was 21.97 kg/m2. Sixty-one patients (44.5%) showed low BMD (osteopenia and osteoporosis) based on the WHO criteria. The median BMD was −0.80 g/cm2 (IQR, −1.5 to −0.2). The prevalence rate of low BMD was 37% in those who were aged 20–29 years, 45.2% in those who were aged 30–39 years, 45.2% in those who were aged 40–49 years, 45.8% in those who were aged 50–59 years, and 53.8% in those who were aged ≧60 years. More than half of patients (50.4%, 69/137) were younger than 40 years. Compared with normal BMD group, the low BMD group has a higher proportion of secondary hyperparathyroidism (18.0% vs 5.3%, p: 0.026) and a lower median C-terminal FGF23 level (48.92 vs 62.61 pg/ml, p: 0.008). Univariate and multivariate analyses of the factors associated with low BMD. We found that only serum intact-parathyroid hormone (iPTH) > 69 pg/ml (OR, 3.86; 95% CI, 1.14–13.09) was statistically significant associated with low BMD in multivariate analysis. Conclusions: This cohort-based survey showed a high prevalence of low BMD among HIV-infected adults which included young-age patient in an university hospital. Secondary hyperparathyroidism was significantly associated with low BMD. There was no association between FGF23 and low BMD. Keywords: Low bone mineral density, Fibroblast growth factor 23, HIV, Hyperparathyroidism, Osteopenia

In this study, we have successfully prepared gallium oxide resistive random access memory by RF magnetron sputtering. The various Ar/O2 gas flow was carefully controlled by different oxygen concentration to obtain proper Ga2O3 film. It was demonstrated that the performance of the devices was improved by optimizing oxygen vacancy through deposition condition. Consequently, the sample with 25% of oxygen concentration exhibited the outstanding electrical properties with maximum cycles of 220, an Ion/Ioff ratio of 5 × 104, retention time of 104 s, high resistance state /low resistance state ratio of 7 × 105 under 0.1V read voltage.

The magnesium oxide is one of the promising candidate's materials that can act as solar blind photodetectors. However, the intrinsically low thermal conductivity of MgO, which is restrict the application in electric device. The magnesium oxide exhibits the poor conductivity which could improved by doing method. This paper fabricated magnesium indium oxide (MgInO) solar-blind photodetectors by doping indium oxide with magnesium oxide through co-sputtering deposition method. The photodetector comprises a bottom glass substrate, an MgInO thin film, and an interdigitated gold electrode to complete the metal-semiconductor-metal structure of the solar-blind photodetector. The experimental results indicate that the photo-to-dark-current ratio is 1.4 × 104, and the responsivity is 1.47 A/W when a reverse bias voltage of 2 V is applied. Furthermore, the noise equivalent power and detectivity are 7.77×10-11 W and 1.75×1011 cm H0.5W-1 with a 2 V bias voltage, respectively.

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions. Keywords: Endocrine system diseases, hypophysitis, immunotherapy

Coronary artery disease (CAD) is a common major disease. Revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) could relieve symptoms and myocardial ischemia. As the treatment improves and evolves, the number of aged patients with complex diseases and multiple comorbidities gradually increases. Furthermore, in patients with multivessel disease, 3-vessel PCI may lead to a higher risk of complications during the procedure, leading to further ischemia and higher long-term mortality than PCI for one vessel or two vessels. Nevertheless, the risk factors for accurately predicting patient mortality after 3-vessel PCI are unclear. Thus, a new risk prediction model for primary PCI (PPCI) patients’ needs to be established to help physicians and patients make decisions more quickly and accurately. This research aimed to construct a prediction model and find which risk factors will affect mortality in 3-vessel PPCI patients. This nationwide population-based cohort study crossed multiple hospitals and selected 3-vessel PPCI patients from January 2007 to December 2009. Then five different single machine learning methods were applied to select significant predictors and implement ensemble models to predict the mortality rate. Of the 2337 patients who underwent 3-vessel PPCI, a total of 1188 (50.83%) survived and 1149 (49.17%) died. Age, congestive heart failure (CHF), and chronic renal failure (CRF) are mortality’s most important variables. When CRF patients accept 3-vessel PPCI at ages between 68–75, they will possibly have a 94% death rate; Furthermore, this study used the top 15 variables averaged by each machine learning method to make a prediction model, and the ensemble learning model can accurately predict the long-term survival of 3-vessel PPCI patients, the accurate predictions rate achieved in 88.7%. Prediction models can provide helpful information for the clinical physician and enhance clinical decision-making. Furthermore, it can help physicians quickly identify the risk features, design clinical trials, and allocate hospital resources effectively.

Fitness is important in people’s lives. Good fitness habits can improve cardiopulmonary capacity, increase concentration, prevent obesity, and effectively reduce the risk of death. Home fitness does not require large equipment but uses dumbbells, yoga mats, and horizontal bars to complete fitness exercises and can effectively avoid contact with people, so it is deeply loved by people. People who work out at home use social media to obtain fitness knowledge, but learning ability is limited. Incomplete fitness is likely to lead to injury, and a cheap, timely, and accurate fitness detection system can reduce the risk of fitness injuries and can effectively improve people’s fitness awareness. In the past, many studies have engaged in the detection of fitness movements, among which the detection of fitness movements based on wearable devices, body nodes, and image deep learning has achieved better performance. However, a wearable device cannot detect a variety of fitness movements, may hinder the exercise of the fitness user, and has a high cost. Both body-node-based and image-deep-learning-based methods have lower costs, but each has some drawbacks. Therefore, this paper used a method based on deep transfer learning to establish a fitness database. After that, a deep neural network was trained to detect the type and completeness of fitness movements. We used Yolov4 and Mediapipe to instantly detect fitness movements and stored the 1D fitness signal of movement to build a database. Finally, MLP was used to classify the 1D signal waveform of fitness. In the performance of the classification of fitness movement types, the mAP was 99.71%, accuracy was 98.56%, precision was 97.9%, recall was 98.56%, and the F1-score was 98.23%, which is quite a high performance. In the performance of fitness movement completeness classification, accuracy was 92.84%, precision was 92.85, recall was 92.84%, and the F1-score was 92.83%. The average FPS in detection was 17.5. Experimental results show that our method achieves higher accuracy compared to other methods.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Thalamic hemorrhage bears the worst outcome among supratentorial intracerebral hemorrhage (ICH). Minimally invasive endoscopic-aided surgery (MIS) has been proved to be safe and effective in evacuating ICH. However, the ideal timing of MIS is still a controversy. In this study, we present our experience in the treatment of patients with thalamic hemorrhage by ultrarapid MIS evacuation. This retrospective analysis enrolled seven patients treated with ultrarapid MIS evacuation of thalamic hemorrhage. Seven patients treated with EVD with similar ICH score were included as match control. Primary endpoints included rebleeding, morbidity, and mortality. Hematoma evacuation rate was evaluated by comparing the pre- and postoperative computed tomography (CT) scans. Glasgow Outcome Scale Extended (GOSE) and modified Rankin Score (mRS) were noted at the 6-month and 1-year postoperative follow-up. Among the seven patients, six were accompanied with intraventricular hemorrhage. All patients received surgery within 6 hours after the onset of stroke. The mean hematoma volume was 35 mL, and the mean operative time was 116.4 minutes. The median hematoma evacuation rate was 74.9%. There was no rebleeding or death reported after the surgery. The median GOSE and mRS were 3 and 5, respectively, at 6 months postoperatively. Further, 1-year postoperative median GOSE and mRS were 3 and 5, respectively. The data suggest that the ultrarapid MIS technique is a safe and effective way in the management of selected cases with thalamic hemorrhage, with favorable long-term functional outcomes. However, a large, prospective, randomized-controlled trial is needed to confirm these findings.

This paper proposes a framework for screening and evaluating seismic performance of river earth embankments on liquefiable foundation soils. The framework is executed in the order of simplest screening by soil liquefaction potential map to preliminary and detailed evaluation of seismic performance of embankment according to the sufficiency of data and the complexity and accuracy of the methods. The seismic performances of embankments are classified into four levels based on the seismic-induced crest settlement. The method used for preliminary evaluation is based only on the factors of safety of foundation soils against liquefaction and the embankment slope against sliding. The static softening method (SSM) and dynamic effective stress method (DESM) are suggested for detailed evaluation of seismic performance. SSM is a static FDM or FEM analysis for estimating liquefaction-induced settlement by weakening the strength of the liquefied foundation soil under the action of the self-weight of the embankment. However, DESM is a dynamic history analysis for estimating liquefaction-induced settlement by simulating the generation and dissipation of pore water pressure in the liquefaction process of foundation soils under the action of the self-weight of the soil embankment and its seismic inertial force. The damaged embankment of the Maoluo River in the 1999 Chi-Chi earthquake was used as a case to demonstrate the feasibility of this framework. The results showed that the simpler the adopted method is, the more conservative the estimated settlement.

Venous needle dislodgement (VND) is a major healthcare safety concern in patients undergoing hemodialysis. Although VND is uncommon, it can be life-threatening. The main objective of this study was to implement a real-time multi-bed monitoring system for VND by combining a novel leakage-detection device and IoMT (Internet of Medical Things) technology. The core of the system, the Acusense IoMT platform, consisted of a novel leakage-detection patch comprised of multiple concentric rings to detect blood leakage and quantify the leaked volume. The performance of the leakage-detection system was evaluated on a prosthetic arm and clinical study. Patients with a high risk of blood leakage were recruited as candidates. The system was set up in a hospital, and the subjects were monitored for 2 months. During the pre-clinical simulation experiment, the system could detect blood leakage volumes from 0.3 to 0.9 mL. During the test of the IoMT system, the overall success rate of tests was 100%, with no lost data packets. A total of 701 dialysis sessions were analyzed, and the accuracy and sensitivity were 99.7% and 90.9%, respectively. Evaluation questionnaires showed that the use of the system after training changed attitudes and reduced worry of the nursing staff. Our results show the feasibility of using a novel detector combined with an IoMT system to automatically monitor multi-bed blood leakage. The innovative concentric-circle design could more precisely control the warning blood-leakage threshold in any direction to achieve clinical cost-effectiveness. The system reduced the load on medical staff and improved patient safety. In the future, it could also be applied to home hemodialysis for telemedicine during the era of COVID-19.

Objective: In brain machine interfaces (BMIs), the functional mapping between neural activities and kinematic parameters varied over time owing to changes in neural recording conditions. The variability in neural recording conditions might result in unstable long-term decoding performance. Relevant studies trained decoders with several days of training data to make them inherently robust to changes in neural recording conditions. However, these decoders might not be robust to changes in neural recording conditions when only a few days of training data are available. In time-series prediction and feedback control system, an error feedback was commonly adopted to reduce the effects of model uncertainty. This motivated us to introduce an error feedback to a neural decoder for dealing with the variability in neural recording conditions.Approach: We proposed an evolutionary constructive and pruning neural network with error feedback (ECPNN-EF) as a neural decoder. The ECPNN-EF with partially connected topology decoded the instantaneous firing rates of each sorted unit into forelimb movement of a rat. Furthermore, an error feedback was adopted as an additional input to provide kinematic information and thus compensate for changes in functional mapping. The proposed neural decoder was trained on data collected from a water reward-related lever-pressing task for a rat. The first 2 days of data were used to train the decoder, and the subsequent 10 days of data were used to test the decoder.Main Results: The ECPNN-EF under different settings was evaluated to better understand the impact of the error feedback and partially connected topology. The experimental results demonstrated that the ECPNN-EF achieved significantly higher daily decoding performance with smaller daily variability when using the error feedback and partially connected topology.Significance: These results suggested that the ECPNN-EF with partially connected topology could cope with both within- and across-day changes in neural recording conditions. The error feedback in the ECPNN-EF compensated for decreases in decoding performance when neural recording conditions changed. This mechanism made the ECPNN-EF robust against changes in functional mappings and thus improved the long-term decoding stability when only a few days of training data were available.

AimThe addition of maternal age to fasting plasma glucose (FPG) at 24-28 gestational weeks improves the performance of GDM screening as maternal age increases. However, this method delays the diagnosis of GDM. Since FPG at the first prenatal visit (FPV) is a screening option for pre-existing diabetes, we evaluated the performance of age plus FPG at the FPV to reduce the need for the OGTT.MethodsPregnant women were recruited consecutively in 2013-2018 (the training cohort) and 2019 (the validation cohort). We excluded women with twin pregnancies, unavailable FPG at the FPV or OGTT data, pre-pregnancy diabetes, or a history of GDM. All participants underwent FPG and haemoglobin A1c (HbA1c) at the FPV and received 75-g OGTT at 24-28 gestational weeks if FPG at the FPV was ResultsThe incidence of GDM increased with age. The "FPG at the FPV" algorithm reduced OGTT% to 68.8% with the FPG cutoff at 79 mg/dl. The "age plus FPG at the FPV" algorithm, with the cutoff of 114, further reduced OGTT% to 58.3%, with the sensitivity of 90.7% (9.3% GDM missed) and the specificity of 100%. These findings were replicated in the validation cohort.ConclusionsScreening GDM by maternal age plus FPG at the FPV can reduce OGTT%, especially in populations with a significant proportion of pregnant women with advanced ages.