Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia—a pilot study

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming.Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65–97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission.Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696).Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems

Effects of Trait Anxiety on Error Processing and Post-error Adjustments: An Event-Related Potential Study With Stop-Signal Task

The present study aimed to use event-related potentials with the stop-signal task to investigate the effects of trait anxiety on inhibitory control, error monitoring, and post-error adjustments. The stop-signal reaction time (SSRT) was used to evaluate the behavioral competence of inhibitory control. Electrophysiological signals of error-related negativity (ERN) and error positivity (Pe) were used to study error perception and error awareness, respectively. Post-error slowing (PES) was applied to examine the behavioral adjustments after making errors. The results showed that SSRT and PES did not differ significantly between individuals with high trait anxiety (HTA) and those with low trait anxiety (LTA). However, individuals with HTA demonstrated reduced ERN amplitudes and prolonged Pe latencies than those with LTA. Prolonged Pe latencies were also significantly associated with poorer post-error adjustments. In conclusion, HTA led to reduced cortical responses to error monitoring. Furthermore, inefficient conscious awareness of errors might lead to maladaptive post-error adjustments

Assessing the Decision-Making Process in Human-Robot Collaboration Using a Lego-like EEG Headset

Human-robot collaboration (HRC) has become an emerging field, where the use of a robotic agent has been shifted from a supportive machine to a decision-making collaborator. A variety of factors can influence the effectiveness of decision-making processes during HRC, including the system-related (e.g., robot capability) and human-related (e.g., individual knowledgeability) factors. As a variety of contextual factors can significantly impact the human-robot decision-making process in collaborative contexts, the present study adopts a Lego-like EEG headset to collect and examine human brain activities and utilizes multiple questionnaires to evaluate participants’ cognitive perceptions toward the robot. A user study was conducted where two levels of robot capabilities (high vs. low) were manipulated to provide system recommendations. The participants were also identified into two groups based on their computational thinking (CT) ability. The EEG results revealed that different levels of CT abilities trigger different brainwaves, and the participants’ trust calibration of the robot also varies the resultant brain activities

Statistical identification of gene association by CID in application of constructing ER regulatory network

<p>Abstract</p> <p>Background</p> <p>A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating <it>in silico </it>inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A).</p> <p>Results</p> <p>The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's <it>t</it>-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays.</p> <p>Conclusion</p> <p>CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers.</p> <p>Availability</p> <p>the implementation of CID in R codes can be freely downloaded from <url>http://homepage.ntu.edu.tw/~lyliu/BC/</url>.</p

Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer

IntroductionThe failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.MethodsWe conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.ResultsSerum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 &gt; 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.ConclusionWe found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation

Hyperbaric oxygen therapy as rescue therapy for pediatric frosted branch angiitis with Purtscher-like retinopathy: A case report

IntroductionFrosted branch angiitis (FBA) is an uncommon uveitis characterized by fulminant retinal vasculitis. Purtscher-like retinopathy (PuR) is a rare retinal angiopathy associated with a non-traumatic etiology. Both FBA and PuR can cause profound visual impairments.Case reportWe describe the case of a 10-year-old male who presented with sudden bilateral painless visual loss due to FBA with concurrent PuR, with notable viral prodrome 1 month prior to presentation. Systemic investigations revealed a recent herpes simplex virus 2 infection with a high titer of IgM, positive antinuclear antibody (ANA) (1:640), and abnormal liver function tests. After administration of systemic corticosteroids, anti-viral agents, and subsequent immunosuppressive medications, the FBA was gradually alleviated. However, fundoscopy and optical coherence tomography (OCT) revealed persistent PuR and macular ischemia. Hence, hyperbaric oxygen therapy was administered as a rescue strategy, which resulted in gradual bilateral visual acuity improvement.ConclusionHyperbaric oxygen therapy may be a beneficial rescue treatment for retinal ischemia secondary to FBA with PuR

A Novel Selective JAK2 Inhibitor Identified Using Pharmacological Interactions

The JAK2/STAT signaling pathway mediates cytokine receptor signals that are involved in cell growth, survival and homeostasis. JAK2 is a member of the Janus kinase (JAK) family and aberrant JAK2/STAT is involved with various diseases, making the pathway a therapeutic target. The similarity between the ATP binding site of protein kinases has made development of specific inhibitors difficult. Current JAK2 inhibitors are not selective and produce unwanted side effects. It is thought that increasing selectivity of kinase inhibitors may reduce the side effects seen with current treatment options. Thus, there is a great need for a selective JAK inhibitor. In this study, we identified a JAK2 specific inhibitor. We first identified key pharmacological interactions in the JAK2 binding site by analyzing known JAK2 inhibitors. Then, we performed structure-based virtual screening and filtered compounds based on their pharmacological interactions and identified compound NSC13626 as a potential JAK2 inhibitor. Results of enzymatic assays revealed that against a panel of kinases, compound NSC13626 is a JAK2 inhibitor and has high selectivity toward the JAK2 and JAK3 isozymes. Our cellular assays revealed that compound NSC13626 inhibits colorectal cancer cell (CRC) growth by downregulating phosphorylation of STAT3 and arresting the cell cycle in the S phase. Thus, we believe that compound NSC13626 has potential to be further optimized as a selective JAK2 drug

Amyloid-Beta (Aβ) D7H Mutation Increases Oligomeric Aβ42 and Alters Properties of Aβ-Zinc/Copper Assemblies

Amyloid precursor protein (APP) mutations associated with familial Alzheimer's disease (AD) usually lead to increases in amyloid β-protein (Aβ) levels or aggregation. Here, we identified a novel APP mutation, located within the Aβ sequence (AβD7H), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased Aβ production, Aβ42/40 ratio and prolonged Aβ42 oligomer state with higher neurotoxicity. Because the D7H mutant Aβ has an additional metal ion-coordinating residue, histidine, we speculate that this mutation may promote susceptibility of Aβ to ion. When co-incubated with Zn2+ or Cu2+, AβD7H aggregated into low molecular weight oligomers. Together, the D7H mutation could contribute to AD pathology through a “double punch” effect on elevating both Aβ production and oligomerization. Although the pathogenic nature of this mutation needs further confirmation, our findings suggest that the Aβ N-terminal region potentially modulates APP processing and Aβ aggregation, and further provides a genetic indication of the importance of Zn2+ and Cu2+ in the etiology of AD