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Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p

Background: Patients suffering from chronic pain frequently ask pharmacists for advice. Aims: This study was prompted by inadequacies in the available body of literature reporting on pharmacists’ experiences with providing care for patients with chronic pain in the community setting. Methods: A qualitative investigation of Ontario community pharmacists’ experiences was carried out. Participants were interviewed using a semistructured guide. Interviews were analyzed using thematic analysis, influenced by grounded theory. Results: This study revealed that pharmacists were knowledgeable and empathetic toward patient concerns. Challenges in their role included financial factors, patient access to multimodal treatment options, potential for harm associated with opioid use, inadequate monitoring, and gaps in training. Conclusions: This study reports community and Family Health Team pharmacists’ experiences caring for patients with chronic pain and perceptions of their professional role, including strengths and limitations, and identifies perceived challenges in the health care system.

Abstract Background Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking. Methods We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies. Results Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant. Conclusion To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.

Abstract Background An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315–324, Spike333–338, Spike648–663, Spike1064–1079) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC class I and MHC class II molecules respectively. The peptides (Nucleocapsid66–75, Nucleocapsid104–112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

Popular scientific reading books, as the bridge between scientific academic research and general public’s knowledge capital, could raise scientific literacy and facilitate comprehension for general public. Popular scientific reading books could attract children to read because of vivid exhibition of text and illustrating graphs. However, some scientific reading books are still too difficult for children to read since they are not designed for children particularly in Taiwan and reading capacity among children are heterogeneous. One promising education strategy is to recommend more scientific reading books corresponding to textbook lessons, which could raise children’s interest in exploring science and further reading. In US, Lexile framework for reading has been developed and applied for English books to assist in more efficient and objective text leveling. For recent years, Chinese Readability Index Explorer (CRIE) has been developed for Chinese text. The main research question here is, for Chinese scientific reading books, whether there are differences in text leveling between system’s (CRIE) and experts’ identification. In our research, we invite teacher librarians to recommend popular scientific reading books, identify the grade levels, and assign these books to corresponding textbook lessons. We not only discuss the principles and criteria of experts’ leveling, compare the different results between CRIE and experts’ opinions, but also investigate the reasons behind these differences. (Article content in Chinese with English extended abstract)

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013–2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.

Abstract Background The objective of this study was to evaluate the clinical effect and correlation between preoperative imaging parameters and the clinical effect of endoscopic transforaminal decompression for lumbar spinal stenosis. Methods In this prospective study, 87 patients from Shanxi Province People’s Hospital met the criteria for lumbar spinal stenosis and were recruited from June 2014 to January 2016. These patients underwent endoscopic transforaminal decompression. The clinical symptoms were evaluated by VAS, ODI, and claudication at 3 and 6 months after surgery. The overall clinical efficacy was evaluated using the MacNab score. Yellow ligament thickness and area of the dural sac were examined by MRI. Bony vertebral canal area, real spinal canal area, nerve root canal bony area, nerve root canal real area, distance between the articular joints, and vertebral canal sagittal diameter were examined by CT. The soft tissue invasion ratio of the vertebral canal and the invasion ratio of the nerve root canal were calculated. Correlations between imaging parameters and age, sex, and clinical efficacy were examined. Results The MacNab scores were excellent in 47% of cases, good in 34%, generally good in 8%, and poor in 11%. VAS, ODI, and claudication were significantly improved compared with the preoperative values (P

Abstract Background The compositions of venous (red blood cell–rich) and arterial (platelet‐rich) thrombi are mediated by distinct pathophysiologic processes; however, fibrin is a major structural component of both. The transglutaminase factor XIII (FXIII) stabilizes fibrin against mechanical and biochemical disruption and promotes red blood cell retention in contracted venous thrombi. Previous studies have shown factor XIII (FXIII) inhibition decreases whole blood clot mass and therefore, may be a therapeutic target for reducing venous thrombosis. The role of FXIII in arterial thrombogenesis is less studied, and the particular contribution of platelet FXIII remains unresolved. Objective To determine whether FXIII reduction prevents experimental arterial thrombogenesis. Methods Using wild‐type mice and mice with genetically imposed deficiency in FXIII, we measured thrombus formation and stability following ferric chloride–induced arterial thrombosis. We also determined the impact of FXIII on the mass of contracted platelet‐rich plasma clots. Results Following vessel injury, F13a+/+, F13a+/−, and F13a−/− mice developed occlusive arterial thrombi. FXIII deficiency did not significantly reduce the incidence or prolong the time to occlusion. FXIII deficiency also did not alter the timing of reflow events or decrease platelet‐rich clot mass. Conclusions FXIII does not significantly alter the underlying pathophysiology of experimental arterial thrombus formation.

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment.

An observer is a crucial part of the sensorless control of a permanent magnet synchronous motor (PMSM). An observer, based on mathematical equations, depends on information regarding several parameters of the controlled motor. If the motor is replaced, then we need to know the motor parameter values and reset the observer’s parameters. This article discusses an intelligent observer that can be used for several motors with different parameters. The proposed intelligent observer was developed using machine learning methods. This observer’s core algorithm is a modified Jordan neural network. It processes Iα, Iβ, vα, and vβ to produce Sin θ and Cos θ values. It is combined with a phase-locked loop function to generate position and speed feedback information. The offline learning process is carried out using data acquired from the simulations of PMSM motors. This study used five PMSMs with different parameters, three as the learning reference sources and two as testing sources. The proposed intelligent observer was successfully used to control motors with different parameters in both simulation and experimental hardware. The average error in position estimated for the simulation was 0.0078 p.u and the error was 0.0100 p.u for the experimental realization.

The potential of machine learning and novel computing architecture can be exploited in the immediate future if more efficient hardware is developed that meets the special requirements of bio-inspired computing or unconventional computing schemes [...]

We constrain anisotropic cosmic birefringence using four-point correlations of even-parity E-mode and odd-parity B-mode polarization in the cosmic microwave background measurements made by the POLARization of the Background Radiation (POLARBEAR) experiment in its first season of observations. We find that the anisotropic cosmic birefringence signal from any parity-violating processes is consistent with zero. The Faraday rotation from anisotropic cosmic birefringence can be compared with the equivalent quantity generated by primordial magnetic fields if they existed. The POLARBEAR nondetection translates into a 95% confidence level (C.L.) upper limit of 93 nanogauss (nG) on the amplitude of an equivalent primordial magnetic field inclusive of systematic uncertainties. This four-point correlation constraint on Faraday rotation is about 15 times tighter than the upper limit of 1380 nG inferred from constraining the contribution of Faraday rotation to two-point correlations of B-modes measured by Planck in 2015. Metric perturbations sourced by primordial magnetic fields would also contribute to the B-mode power spectrum. Using the POLARBEAR measurements of the B-mode power spectrum (two-point correlation), we set a 95% C.L. upper limit of 3.9 nG on primordial magnetic fields assuming a flat prior on the field amplitude. This limit is comparable to what was found in the Planck 2015 two-point correlation analysis with both temperature and polarization. We perform a set of systematic error tests and find no evidence for contamination. This work marks the first time that anisotropic cosmic birefringence or primordial magnetic fields have been constrained from the ground at subdegree scales.

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated.Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system.Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies.Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively.Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.

Resistive random-access memory (RRAM) devices have drawn increasing interest for the simplicity of its structure, low power consumption and applicability to neuromorphic computing. By combining analog computing and data storage at the device level, neuromorphic computing system has the potential to meet the demand of computing power in applications such as artificial intelligence (AI), machine learning (ML) and Internet of Things (IoT). Monolayer rhenium diselenide (ReSe2), as a two-dimensional (2D) material, has been reported to exhibit non-volatile resistive switching (NVRS) behavior in RRAM devices with sub-nanometer active layer thickness. In this paper, we demonstrate stable multiple-step RESET in ReSe2 RRAM devices by applying different levels of DC electrical bias. Pulse measurement has been conducted to study the neuromorphic characteristics. Under different height of stimuli, the ReSe2 RRAM devices have been found to switch to different resistance states, which shows the potentiation of synaptic applications. Long-term potentiation (LTP) and depression (LTD) have been demonstrated with the gradual resistance switching behaviors observed in long-term plasticity programming. A Verilog-A model is proposed based on the multiple-step resistive switching behavior. By implementing the LTP/LTD parameters, an artificial neural network (ANN) is constructed for the demonstration of handwriting classification using Modified National Institute of Standards and Technology (MNIST) dataset.

This study aimed to (1) explore the correlated influential factors that promote consumers' sharing behaviors of electronic coupons, (2) identify relevant knowledge gaps on e-coupon sharing, and (3) develop a theoretical model to explain the e-coupon sharing behavior of consumers. This study suggested that familiarity and professionalism of the referral source have significant and positive impacts on the feeling of credibility of e-coupons, which promote consumers' willingness to share. Moreover, this research used electronic coupons as the product from (1) the concept of social marketing and (2) the perspective of the social sharing behavior of consumers. The research findings of this study showed that (1) community-based social marketing is covered in the social norm as social individuals frequently hope to share benefits with others. (2) People's sharing purpose is to promote their established social relationship via sharing the benefits to others. In this case, benefits referred to advantageous products' attributes and values consumers found on the products such as credibility of the products. (3) The interlaced display of products and social psychology in the field of social marketing was also discussed in this study. In short, the research results of this study theoretically contributed to indicate the connection mechanism between (A) social benefit-sharing behavior and (B) product benefits. That is to say, the feeling of credibility and willingness to shares are covered by the social benefit-sharing behavior mechanism, while the product-benefit mechanism covers professionalism, feeling of credibility and willingness to share. Note that the (A) social benefit-sharing behavior mechanism works in the form of social norms in sharing benefits to an individual's social networks; the (B) product-benefit mechanism work in the form of product values and attributes.

Abstract Patients with hypertension have increased risk of sudden death, but the impact of blood pressure control in sudden death is not clear. To better understand potential opportunities to prevent sudden, we assessed blood pressure control, comorbidities, and the number of recent medical encounters among all‐cause sudden death victims. Less than 40% of sudden death victims with hypertension had controlled blood pressure prior to death. Furthermore, increased frequency of medical visits and number of comorbidities were associated with better blood pressure control Strategies to address clinical inertia in hypertension treatment particularly for patients with fewer comorbidities may attenuate the risk of sudden death.