Highly Sulfated Forms of Heparin Sulfate Are Involved in Japanese Encephalitis Virus Infection

AbstractJapanese encephalitis virus (JEV) infects a broad range of cell types in vitro, though little is known about the initial events of JEV infection. In the present study, we found that highly sulfated glycosaminoglycans (GAGs) are involved in infection of both neurovirulent (RP-9) and attenuated (RP-2ms) JEV strains. Competition experiments using highly sulfated GAGs, heparin and dextran sulfate, demonstrated an inhibition of JEV's attachment and subsequent infection of BHK-21 cells. Treatment of target cells by a potent sulfation inhibitor, sodium chlorate, greatly reduced viral binding ability as well as infection, suggesting a critical role of GAGs' sulfation status on the cellular surface in JEV infection. This phenomenon was confirmed by the manifestation of a distinct binding efficiency of JEV to the wild-type CHO cell line and its mutants with defects in GAG biosynthesis. We also demonstrated the binding of JEV particles and virus envelope glycoprotein to immobilized heparin beads. Furthermore, the addition of heparin suppressed the cytopathic effects induced by JEV infection in cultured cells. Our results establish that the highly sulfated form of GAGs on cell surfaces plays a determining role in the early stage of in vitro JEV infection

Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern Taiwan

Background/PurposeLong-term oxygen therapy has become standard treatment for patients with chronic respiratory insufficiency. However, patterns of long-term home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator systems are commonly used in Taiwan, but liquid oxygen delivery systems are portable and may provide advantages over the concentrator system. This study compared oxygen usage between patients from a liquid oxygen group (LOG) and an oxygen concentrator group (OCG). The authors also assessed the physiologic responses of patients with chronic obstructive pulmonary disease (COPD) to ambulatory oxygen use at home.MethodsThe study used a retrospective, cross-sectional, observational survey design. The LOG comprised 42 patients, and the OCG comprised 102 patients. We recruited participants in northern Taiwan from July 2009 to April 2010. The questionnaire instruments that were used to collect data consisted of three parts: demographic characteristics, devices used in respiratory care, and activity status with portable oxygen. Two-minute walking tests were performed on COPD patients in their homes.ResultsCOPD was the most common diagnosis in our study, with more than 50% of patients who received oxygen long term in both groups having received this diagnosis. The LOG used oxygen for an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8% of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in significantly more outdoors activities (p=0.002) and reported traveling with oxygen more often (p<0.001) than the OCG patients. For patients with the same dyspnea level of COPD severity, those using liquid oxygen had a lower increase in pulse rate after the walking test, in comparison with the concentrator users.ConclusionPatients in the LOG used oxygen for longer hours, went on more outings, and were more likely to travel with oxygen than patients in the OCG. Being ambulatory with liquid oxygen might enable patients with COPD to walk more effectively

Design of FIR Fractional Delay Filter Based on Maximum Signal-to-Noise Ratio Criterion

Abstract-In this paper, a new approach to the design of digital FIR fractional delay filter with consideration of noise attenuation is presented. The design is based on the maximization of signal-to-noise ratio (SNR) at the output of the fractional delay filter under the constraint that actual frequency response and ideal response have several same derivatives at the prescribed frequency point. The optimal filter coefficients are obtained from the generalized eigenvector associate with maximum eigenvalue of a pair of matrices. Numerical examples are demonstrated to show the proposed method provides higher SNR than the conventional FIR fractional delay filter design methods without considering the noise attenuation

Deductive Verification of Chain-of-Thought Reasoning

Large Language Models (LLMs) significantly benefit from Chain-of-Thought (CoT) prompting in performing various reasoning tasks. While CoT allows models to produce more comprehensive reasoning processes, its emphasis on intermediate reasoning steps can inadvertently introduce hallucinations and accumulated errors, thereby limiting models' ability to solve complex reasoning tasks. Inspired by how humans engage in careful and meticulous deductive logical reasoning processes to solve tasks, we seek to enable language models to perform explicit and rigorous deductive reasoning, and also ensure the trustworthiness of their reasoning process through self-verification. However, directly verifying the validity of an entire deductive reasoning process is challenging, even with advanced models like ChatGPT. In light of this, we propose to decompose a reasoning verification process into a series of step-by-step subprocesses, each only receiving their necessary context and premises. To facilitate this procedure, we propose Natural Program, a natural language-based deductive reasoning format. Our approach enables models to generate precise reasoning steps where subsequent steps are more rigorously grounded on prior steps. It also empowers language models to carry out reasoning self-verification in a step-by-step manner. By integrating this verification process into each deductive reasoning stage, we significantly enhance the rigor and trustfulness of generated reasoning steps. Along this process, we also improve the answer correctness on complex reasoning tasks. Code will be released at https://github.com/lz1oceani/verify_cot

Association of maternal and cord plasma total, free and bioavailable 25-hyrodroxyvitamin D with neonatal anthropometric measurements at birth: a preliminary study in a private hospital

Introduction: 25-hydroxyvitamin D (25OHD) is the principal biomarker of vitamin D status. In circulation, 25OHD is primarily bound to vitamin D binding protein (VDBP), leaving a small proportion bound to albumin and as free form. Previous studies have suggested that free 25OHD is better correlated with health outcomes. However, in pregnancy where VDBP level is extremely elevated, the correlations between free 25OHD with health outcomes are far from conclusive. Here we show the associations of maternal and cord total, free and bioavailable 25OHD con-currently with neonatal anthropometric measurements in healthy pregnant mothers-neonates pairs. Method: Total 25OHD level was measured by using chemiluminescent immunoassay. Free and bioavailable 25OHD were calculated using published mathematical models. Results: The results showed that birth weight and head circumference were negatively associated with maternal total 25OHD but not significantly associated with free and bioavailable 25OHD. There were no significant associations between cord total, free and bioavailable 25OHD with any of the neonatal anthropometric measurements. Conclusion: The outcomes of this study should encourage further research in a larger sample size. Notably, future research could lead to the establishment of causative relationships and plausible mechanisms between maternal and cord 25OHD with neonatal anthropometric measurements

Effects of implementation of an online comprehensive antimicrobial-stewardship program in ICUs: A longitudinal study

AbstractBackground/purposeThe long-term effects of antimicrobial-stewardship programs in the intensive care units (ICUs) have not been adequately examined. We evaluated the impact of an online comprehensive antimicrobial stewardship program (OCASP) on the outcomes of patients in 200-bed medical/surgical ICUs over the course of 11 years.MethodsWe analyzed the records of adult patients admitted to ICUs during the 5 years before (n = 27,499) and the 6 years after (n = 33,834) implementation of an OCASP. Antimicrobial consumption, expenditures, duration of treatment, incidence of healthcare-associated infections (HAIs), prevalence of HAIs caused by antimicrobial-resistant strains, and crude or sepsis-related mortality of patients were analyzed. Segmented regression analyses of interrupted time series were used to assess the significance of changes in antimicrobial use.ResultsCompared to the patients in the pre-OCASP period, the patients in the post-OCASP period were older, had greater disease severity, longer ICU stays, and were more likely to receive antimicrobials, but had lower antimicrobial expenditures and crude and sepsis-related mortality. The trend of overall antimicrobial use [slope of defined daily dose/1000 patient-days vs. time) increased significantly before OCASP implementation (p < 0.001), but decreased significantly after implementation (p < 0.01). The administration duration of all classes of antibiotics were significantly shorter (p < 0.001) and the incidences of HAIs were significantly lower (p < 0.001) after implementation. However, there was an increase in the proportion of HAIs caused by carbapenem-resistant Acinetobacter baumannii relative to all A. baumannii infections.ConclusionImplementation of an OCASP in the ICUs reduced antimicrobial consumption and expenditures, but did not compromise healthcare quality

Relationships among Constitution, Stress, and Discomfort in the First Trimester

The purpose of this study was to explore correlations among constitution, stress, and discomfort symptoms during the first trimester of pregnancy. We adopted a descriptive and correlational research design and collected data from 261 pregnant women during their first trimester in southern Taiwan using structured questionnaires. Results showed that (1) stress was significantly and positively correlated with Yang-Xu, Yin-Xu, and Tan-Shi-Yu-Zhi constitutions, respectively; (2) Yin-Xu and Tan-Shi-Yu-Zhi constitutions had significant correlations with all symptoms of discomfort, while Yang-Xu had significant correlations with all symptoms of discomfort except for “running nose”; (3) Tan-Shi-Yu-Zhi constitution and stress were two indicators for “fatigue”; Tan-Shi-Yu-Zhi was the indicator for “nausea”; Yang-Xu and Yin-Xu were indicators for “frequent urination.” Our findings also indicate that stress level affects constitutional changes and that stress and constitutional change affect the incidence of discomfort. This research can help healthcare professionals observe these discomforts and provide individualized care for pregnant women, to nurture pregnant women into neutral-type constitution, minimize their levels of discomfort, and promote the health of the fetus and the mother