Novel enzyme-linked aptamer-antibody sandwich assay and hybrid lateral flow strip for SARS-CoV-2 detection.

We have successfully generated oligonucleotide aptamers (Apts) and monoclonal antibodies (mAbs) targeting the recombinant nucleocapsid (N) protein of SARS-CoV-2. Apts were obtained through seven rounds of systematic evolution of ligands by exponential enrichment (SELEX), while mAbs were derived from the 6F6E11 hybridoma cell line. Leveraging these Apts and mAbs, we have successfully devised two innovative and remarkably sensitive detection techniques for the rapid identification of SARS-CoV-2 N protein in nasopharyngeal samples: the enzyme-linked aptamer-antibody sandwich assay (ELAAA) and the hybrid lateral flow strip (hybrid-LFS). ELAAA exhibited an impressive detection limit of 0.1 ng/mL, while hybrid-LFS offered a detection range of 0.1 - 0.5 ng/mL. In the evaluation using ten nasopharyngeal samples spiked with known N protein concentrations, ELAAA demonstrated an average recovery rate of 92%. Additionally, during the assessment of five nasopharyngeal samples from infected individuals and ten samples from healthy volunteers, hybrid-LFS displayed excellent sensitivity and specificity. Our study introduces a novel and efficient on-site approach for SARS-CoV-2 detection in nasopharyngeal samples. The reliable hybrid Apt-mAb strategy not only advances virus diagnostic methods but also holds promise in combating the spread of related diseases.

Context effects on probability estimation.

Many decisions rely on how we evaluate potential outcomes and estimate their corresponding probabilities of occurrence. Outcome evaluation is subjective because it requires consulting internal preferences and is sensitive to context. In contrast, probability estimation requires extracting statistics from the environment and therefore imposes unique challenges to the decision maker. Here, we show that probability estimation, like outcome evaluation, is subject to context effects that bias probability estimates away from other events present in the same context. However, unlike valuation, these context effects appeared to be scaled by estimated uncertainty, which is largest at intermediate probabilities. Blood-oxygen-level-dependent (BOLD) imaging showed that patterns of multivoxel activity in the dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (VMPFC), and intraparietal sulcus (IPS) predicted individual differences in context effects on probability estimates. These results establish VMPFC as the neurocomputational substrate shared between valuation and probability estimation and highlight the additional involvement of dACC and IPS that can be uniquely attributed to probability estimation. Because probability estimation is a required component of computational accounts from sensory inference to higher cognition, the context effects found here may affect a wide array of cognitive computations.

An altered reward system characterizes chronic migraine with medication overuse headache.

BACKGROUND: Medication overuse headache shares several characteristics with substance use disorders. However, key features of substance use disorders such as increased impulsivity and alterations in reward processing remain little explored in medication overuse headache. METHODS: Temporal discounting and impulsive decision making behavior and the associated brain mechanisms were assessed in 26 chronic migraine patients with medication overuse headache and in 28 healthy controls. Regions-of-interest analyses were first performed for task-related regions, namely the ventral striatum and the ventromedial and dorsomedial prefrontal cortices. Resting-state functional connectivity between these regions were then explored. An additional 27 chronic migraine patients without medication overuse headache were included for comparison in the latter analysis. RESULTS: Patients with medication overuse headache showed steeper temporal discounting behavior than healthy controls. They also showed weaker subjective value representations in the dorsomedial prefrontal cortex, when accepting larger delayed rewards, and in ventral striatum and ventromedial prefrontal cortex, when accepting the smaller immediate reward. Resting-state functional connectivity was reduced among the valuation regions when comparing patients with medication overuse headache to the other two control groups. CONCLUSIONS: Patients with medication overuse headache were characterized by altered processing and dysconnectivity in the reward system during intertemporal choices and in the resting-state.

Base rate neglect and neural computations for subjective weight in decision under uncertainty.

Base rate neglect, an important bias in estimating probability of uncertain events, describes humans' tendency to underweight base rate (prior) relative to individuating information (likelihood). However, the neural mechanisms that give rise to this bias remain elusive. In this study, subjects chose between uncertain prospects where estimating reward probability was essential. We found that when the variability of prior and likelihood information about reward probability were systematically manipulated, prior variability significantly affected the degree to which subjects underweight the base rate of reward probability. Activity in the orbitofrontal cortex, medial prefrontal cortex, and putamen represented the relative subjective weight that reflected such bias. Further, sensitivity to likelihood relative to prior variability in the putamen correlated with individuals' overall tendency to underweight base rate. These findings suggest that in combining prior and likelihood, relative sensitivity to information variability and subjective-weight computations critically contribute to the individual heterogeneity in base rate neglect.

Dynamic combination of sensory and reward information under time pressure.

When making choices, collecting more information is beneficial but comes at the cost of sacrificing time that could be allocated to making other potentially rewarding decisions. To investigate how the brain balances these costs and benefits, we conducted a series of novel experiments in humans and simulated various computational models. Under six levels of time pressure, subjects made decisions either by integrating sensory information over time or by dynamically combining sensory and reward information over time. We found that during sensory integration, time pressure reduced performance as the deadline approached, and choice was more strongly influenced by the most recent sensory evidence. By fitting performance and reaction time with various models we found that our experimental results are more compatible with leaky integration of sensory information with an urgency signal or a decision process based on stochastic transitions between discrete states modulated by an urgency signal. When combining sensory and reward information, subjects spent less time on integration than optimally prescribed when reward decreased slowly over time, and the most recent evidence did not have the maximal influence on choice. The suboptimal pattern of reaction time was partially mitigated in an equivalent control experiment in which sensory integration over time was not required, indicating that the suboptimal response time was influenced by the perception of imperfect sensory integration. Meanwhile, during combination of sensory and reward information, performance did not drop as the deadline approached, and response time was not different between correct and incorrect trials. These results indicate a decision process different from what is involved in the integration of sensory information over time. Together, our results not only reveal limitations in sensory integration over time but also illustrate how these limitations influence dynamic combination of sensory and reward information.

Neural mechanisms for integrating prior knowledge and likelihood in value-based probabilistic inference.

In Bayesian decision theory, knowledge about the probabilities of possible outcomes is captured by a prior distribution and a likelihood function. The prior reflects past knowledge and the likelihood summarizes current sensory information. The two combined (integrated) form a posterior distribution that allows estimation of the probability of different possible outcomes. In this study, we investigated the neural mechanisms underlying Bayesian integration using a novel lottery decision task in which both prior knowledge and likelihood information about reward probability were systematically manipulated on a trial-by-trial basis. Consistent with Bayesian integration, as sample size increased, subjects tended to weigh likelihood information more compared with prior information. Using fMRI in humans, we found that the medial prefrontal cortex (mPFC) correlated with the mean of the posterior distribution, a statistic that reflects the integration of prior knowledge and likelihood of reward probability. Subsequent analysis revealed that both prior and likelihood information were represented in mPFC and that the neural representations of prior and likelihood in mPFC reflected changes in the behaviorally estimated weights assigned to these different sources of information in response to changes in the environment. Together, these results establish the role of mPFC in prior-likelihood integration and highlight its involvement in representing and integrating these distinct sources of information.

Brain stimulation improves cognitive control by modulating medial-frontal activity and preSMA-vmPFC functional connectivity.

Previous research has demonstrated that brain stimulation can improve inhibitory control. However, the neural mechanisms underlying such artificially induced improvement remain unclear. In this study, by coupling anodal transcranial direct current stimulation (atDCS) with functional MRI, we found that atDCS over preSMA effectively improved stopping speed, which was associated with increased BOLD response in the preSMA and ventromedial prefrontal cortex (vmPFC). Furthermore, such atDCS-induced BOLD increase in vmPFC was positively correlated with participants' improvement in stopping efficiency, and the functional connectivity between preSMA and vmPFC increased during successful stop. These results suggest that the rapid behavioral improvement from preSMA brain stimulation involves modulated medial-frontal activity and preSMA-vmPFC functional connectivity.

Advantage management strategy in competition via technological race perspective: empirical evidence from the Taiwanese manufacturing industry.

This study investigated the advantage management strategies of a firm regarding the technological race in the manufacturing sector. This is to reveal whether firms adopt a catch-up or leapfrogging strategy in the competition for innovation. The results show that competition is fierce in the Taiwanese manufacturing industry. Taiwanese manufacturing firms (mostly SMEs) tend to adopt the "catch-up" strategy to keep up with their competitors in order to remain in the technological race. The result indicates that, under financial constraints, Taiwanese manufacturing firms attempt to invest in R&D to catch up with their rivals or to avoid being eliminated from the race.

Exploring the Moderating Effect of Positive and Negative Word-of-Mouth on the Relationship between Health Belief Model and the Willingness to Receive COVID-19 Vaccine.

This study indicates that the positive and negative effects of word-of-mouth (WOM) have an impact and moderating effect on vaccine uptake willingness, which is important to exploring the factors that affect vaccine uptake. We further analyzed the differences in the impact relationship between variables through questionnaire research. Based on the Health Belief Model (HBM) widely used to explore global health issues, this study focuses on Taiwanese residents and uses a questionnaire survey method. Furthermore, this study investigates the impact of various factors in the HBM on the willingness to receive the COVID-19 vaccine when faced with positive and negative word-of-mouth evaluations from the perspective of vaccine recipients, as well as whether WOM evaluations have an interference effect, along with the differences between variables. Practical recommendations are provided based on the research results, which can serve as a reference for future vaccine promotion programs and health promotion. By improving the national vaccination rate and achieving herd immunity, we aim to increase the persuasiveness of word-of-mouth on public healthcare decision-making. We also hope to provide a basis for health promotion and encourage people to make informed decisions about vaccination.

Is it good to hold more cash before the pandemic? A case of Taiwanese firms.

The Covid-19 pandemic poses a great damage to firm performance worldwide. It raises the empirical question that if any factor can help firm perform better during the pandemic. In this study, we hypothesize that firms holding more cash before the pandemic can perform better during the pandemic year in 2020. We collect all listed firms from Taiwan Stock Exchange and test this hypothesis. Adopting a panel-data regression models with fixed effects, we find supportive evidence that pre-saved cash is valuable and can help firms perform better during the pandemic. Cash-rich firms will have a higher return on equity and return on assets. The economic significance is also non-trivial. Our study thus contributes to our understanding of how the pandemic can affect firm business and which lesson we can learn from this pandemic.

Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex.

Evidence from monkeys and humans suggests that the orbitofrontal cortex (OFC) encodes the subjective value of options under consideration during choice. Data from non-human primates suggests that these value signals are context-dependent, representing subjective value in a way influenced by the decision makers' recent experience. Using electrodes distributed throughout cortical and subcortical structures, human epilepsy patients performed an auction task where they repeatedly reported the subjective values they placed on snack food items. High-gamma activity in many cortical and subcortical sites including the OFC positively correlated with subjective value. Other OFC sites showed signals contextually modulated by the subjective value of previously offered goods-a context dependency predicted by theory but not previously observed in humans. These results suggest that value and value-context signals are simultaneously present but separately represented in human frontal cortical activity.

The neural correlates of subjective utility of monetary outcome and probability weight in economic and in motor decision under risk.

In decision under risk, people choose between lotteries that contain a list of potential outcomes paired with their probabilities of occurrence. We previously developed a method for translating such lotteries to mathematically equivalent "motor lotteries." The probability of each outcome in a motor lottery is determined by the subject's noise in executing a movement. In this study, we used functional magnetic resonance imaging in humans to compare the neural correlates of monetary outcome and probability in classical lottery tasks in which information about probability was explicitly communicated to the subjects and in mathematically equivalent motor lottery tasks in which probability was implicit in the subjects' own motor noise. We found that activity in the medial prefrontal cortex (mPFC) and the posterior cingulate cortex quantitatively represent the subjective utility of monetary outcome in both tasks. For probability, we found that the mPFC significantly tracked the distortion of such information in both tasks. Specifically, activity in mPFC represents probability information but not the physical properties of the stimuli correlated with this information. Together, the results demonstrate that mPFC represents probability from two distinct forms of decision under risk.

Hidden diagnosis of Tuberculous pleurisy masked by concomitant Pseudomonas oryzihabitans bacteremia.

The clinical presentations of tuberculous pleurisy are usually nonspecific and have an insidious course, thus resulting in diagnostic challenges. Pseudomonas oryzihabitans is a nonfermenting, oxidase-negative, catalase-positive, Gram-negative bacillus that has rarely been encountered as a human pathogen. We present the case of a 30-year-old male patient who exhibited intermittent fever despite antibiotic treatment for Pseudomonas oryzihabitans bacteremia for 6 days. Tuberculous pleurisy was finally diagnosed by histopathologic and microbiologic studies. He recovered after a 2-week antibiotic course and 6-month antituberculosis treatment.

Economic decision-making compared with an equivalent motor task.

There is considerable evidence that human economic decision-making deviates from the predictions of expected utility theory (EUT) and that human performance conforms to EUT in many perceptual and motor decision tasks. It is possible that these results reflect a real difference in decision-making in the 2 domains but it is also possible that the observed discrepancy simply reflects typical differences in experimental design. We developed a motor task that is mathematically equivalent to choosing between lotteries and used it to compare how the same subject chose between classical economic lotteries and the same lotteries presented in equivalent motor form. In experiment 1, we found that subjects are more risk seeking in deciding between motor lotteries. In experiment 2, we used cumulative prospect theory to model choice and separately estimated the probability weighting functions and the value functions for each subject carrying out each task. We found no patterned differences in how subjects represented outcome value in the motor and the classical tasks. However, the probability weighting functions for motor and classical tasks were markedly and significantly different. Those for the classical task showed a typical tendency to overweight small probabilities and underweight large probabilities, and those for the motor task showed the opposite pattern of probability distortion. This outcome also accounts for the increased risk-seeking observed in the motor tasks of experiment 1. We conclude that the same subject distorts probability, but not value, differently in making identical decisions in motor and classical form.

Does loan growth impact on bank risk?

In the context of competition between domestic banks but also foreign banks become more and more fierce. The increasing penetration of foreign banks brings certain risks to domestic banks. This study was conducted to assess the effect of loan growth on banking risk in Vietnam. The study collects data on 29 banks listed on the Vietnam stock exchange from 2010 to 2020. The results of panel data analysis with Generalized least squares (GLS) have shown a relationship between loan growth and bank risk. In which loan growth has a negative impact on Non-performing loans (NPL), liquidity risk equity on asset (ETA); loan growth has a positive impact on return (ROA). In addition, the study also conducts a comparative assessment by bank size and loan growth rate. The results indicate a difference in loan growth's impact on banks' bank risk with lower and higher assets and lower and higher loan growth rates. From the results of this study, the authors also provide some implications to help banks reduce bank risk based on loan growth strategy.

Pilot production of a sensitive ELISA kit and an immunochromatographic strip for rapid detecting citrinin in fermented rice.

Citrinin (CTN) is a mycotoxin primarily produced by Monascus species. Excess consumption of CTN may lead to nephrotoxicity and hepatotoxicity. A pilot study for commercial production of competitive direct enzyme-linked immunosorbent assay (cdELISA) kit and an immunochromatographic strip (immunostrip) for screening CTN in red yeast rice is established in this study. The coating antibody and the CTN-horse radish peroxidase (HRP) concentrations were optimized to increase the sensitivity and specificity of cdELISA kit. The conjugation methods/ratios of CTN to HRP as well as the long-term stability of kit components were also evaluated. The IC50 and detection limit of the ELISA kit were determined to be 4.1 and 0.2 ng mL-1, respectively. Analysis of 20 red yeast rice samples using ELISA kits revealed the contamination levels of CTN from 64 to 29 404 ng g-1. The on-site rapid detection of CTN with the immunostrip showed that CTN levels in seven samples exceeded the regulatory limit of 5 ppm. Additionally, the coefficient correlation between the results of HPLC and ELISA kits of 20 samples was 0.96. Sensitive and convenient tools at commercial levels for detection of CTN contamination in food are established herein to protect the health of the public.

Obesity Attenuates Ventilator-Induced Lung Injury by Modulating the STAT3-SOCS3 Pathway.

Background: Ventilator-induced lung injury (VILI) is characterized by vascular barrier dysfunction and suppression of alveolar fluid clearance (AFC). Obesity itself leads to chronic inflammation, which may initiate an injurious cascade to the lungs and simultaneously induce a protective feedback. In this study, we investigated the protective mechanism of obesity on VILI in a mouse model. Methods: The VILI model was set up via 6-h mechanical ventilation with a high tidal volume. Parameters including lung injury score, STAT3/NFκB pathway, and AFC were assessed. Mice with diet-induced obesity were obtained by allowing free access to a high-fat diet since the age of 3 weeks. After a 9-week diet intervention, these mice were sacrificed at the age of 12 weeks. The manipulation of SOCS3 protein was achieved by siRNA knockdown and pharmaceutical stimulation using hesperetin. WNK4 knockin and knockout obese mice were used to clarify the pathway of AFC modulation. Results: Obesity itself attenuated VILI. Knockdown of SOCS3 in obese mice offset the protection against VILI afforded by obesity. Hesperetin stimulated SOCS3 upregulation in nonobese mice and provided protection against VILI. In obese mice, the WNK4 axis was upregulated at the baseline, but was significantly attenuated after VILI compared with nonobese mice. At the baseline, the manipulation of SOCS3 by siRNA and hesperetin also led to the corresponding alteration of WNK4, albeit to a lesser extent. After VILI, WNK4 expression correlated with STAT3/NFκB activation, regardless of SOCS3 status. Obese mice carrying WNK4 knockout had VILI with a severity similar to that of wild-type obese mice. The severity of VILI in WNK4-knockin obese mice was counteracted by obesity, similar to that of wild-type nonobese mice only. Conclusions: Obesity protects lungs from VILI by upregulating SOCS3, thus suppressing the STAT3/NFκB inflammatory pathway and enhancing WNK4-related AFC. However, WNK4 activation is mainly from direct NFκB downstreaming, and less from SOCS3 upregulation. Moreover, JAK2-STAT3/NFκB signaling predominates the pathogenesis of VILI. Nevertheless, the interaction between SOCS3 and WNK4 in modulating VILI in obesity warrants further investigation.

Sonographic septation: a useful diagnostic predictor of complicated parapneumonic effusion.

Sonographic septation is associated with prolonged hospitalization and increased mortality in patients diagnosed with empyema. However, it is unknown whether sonographic septation is associated with complicated parapneumonic effusion (CPPE) or the need for invasive procedures among patients with pneumonia. In this retrospective study, we included 180 patients with non-purulent neutrophilic exudative pleural effusion secondary to pulmonary infections such as pneumonia and lung abscess. We performed univariate and multivariate logistic regression analyses, including baseline clinical characteristics, values from blood samples, and sonographic echogenicity, to identify variables correlated with CPPE and the need for invasive procedures. Seventy of the 180 included patients (38.89%) displayed sonographic septation. Multivariate logistic regression analysis identified that sonographic septation (adjusted OR (AOR)=3.38 (95% CI 1.64 to 6.98), p=0.001) and younger age (AOR=2.63 (95% CI 1.24 to 5.58), p=0.012) were independently associated with CPPE. With regard to treatment strategy, sonographic septation (AOR 9.06 (95% CI 3.71 to 22.11), p<0.001) and total serum protein level (AOR=1.80 (95% CI 1.13 to 2.86), p=0.013) were independently associated with the need for subsequent invasive procedures in patients with CPPE using multivariate logistic regression analysis. Sonographic septation is a useful predictor of CPPE and may imply the need for early invasive procedures.

Planning multiple movements within a fixed time limit: the cost of constrained time allocation in a visuo-motor task.

S.-W. Wu, M. F. Dal Martello, and L. T. Maloney (2009) evaluated subjects' performance in a visuo-motor task where subjects were asked to hit two targets in sequence within a fixed time limit. Hitting targets earned rewards and Wu et al. varied rewards associated with targets. They found that subjects failed to maximize expected gain; they failed to invest more time in the movement to the more valuable target. What could explain this lack of response to reward? We first considered the possibility that subjects require training in allocating time between two movements. In Experiment 1, we found that, after extensive training, subjects still failed: They did not vary time allocation with changes in payoff. However, their actual gains equaled or exceeded the expected gain of an ideal time allocator, indicating that constraining time itself has a cost for motor accuracy. In a second experiment, we found that movements made under externally imposed time limits were less accurate than movements made with the same timing freely selected by the mover. Constrained time allocation cost about 17% in expected gain. These results suggest that there is no single speed-accuracy tradeoff for movement in our task and that subjects pursued different motor strategies with distinct speed-accuracy tradeoffs in different conditions.

Learning arbitrary stimulus-reward associations for naturalistic stimuli involves transition from learning about features to learning about objects.

Most cognitive processes are studied using abstract or synthetic stimuli with specific features to fully control what is presented to subjects. However, recent studies have revealed enhancements of cognitive capacities (such as working memory) when processing naturalistic versus abstract stimuli. Using abstract stimuli constructed from distinct visual features (e.g., color and shape), we have recently shown that human subjects can learn multidimensional stimulus-reward associations via initially estimating reward value of individual features (feature-based learning) before gradually switching to learning about reward value of individual stimuli (object-based learning). Here, we examined whether similar strategies are adopted during learning about naturalistic stimuli that are clearly perceived as objects (instead of a combination of features) and contain both task-relevant and irrelevant features. We found that similar to learning about abstract stimuli, subjects initially adopted feature-based learning more strongly before transitioning to object-based learning. However, there were three key differences between learning about naturalistic and abstract stimuli. First, compared with abstract stimuli, the initial learning strategy was less feature-based for naturalistic stimuli. Second, subjects transitioned to object-based learning faster for naturalistic stimuli. Third, unexpectedly, subjects were more likely to adopt feature-based learning for naturalistic stimuli, both at the steady state and overall. These results suggest that despite the stronger tendency to perceive naturalistic stimuli as objects, which leads to greater likelihood of using object-based learning as the initial strategy and a faster transition to object-based learning, the influence of individual features on learning is stronger for these stimuli such that ultimately the object-based strategy is adopted less. Overall, our findings suggest that feature-based learning is a general initial strategy for learning about reward value of all types of multi-dimensional stimuli.