Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution.

The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution, we show that the ACE can be selectively inhibited by ACE2 to prevent cleavage of angiotensin I, even when the concentration of ACE is more than 30-fold higher than that of ACE2. We also show that the activity of ACE2 for cleaving angiotensin peptides is clearly suppressed by the spike protein of SARS-CoV-2. This leads to the relaxation of ACE and the increased probability of accumulation of the principal effector angiotensin II. The spike protein of the SARS-CoV-2 Delta variant is demonstrated to have a much greater impact on the crosstalk than the wild type.

COVID-19 Related Early Google Search Behavior and Health Communication in the United States: Panel Data Analysis on Health Measures.

The COVID-19 outbreak at the end of December 2019 spread rapidly all around the world. The objective of this study is to investigate and understand the relationship between public health measures and the development of the pandemic through Google search behaviors in the United States. Our collected data includes Google search queries related to COVID-19 from 1 January to 4 April 2020. After using unit root tests (ADF test and PP test) to examine the stationary and a Hausman test to choose a random effect model, a panel data analysis is conducted to investigate the key query terms with the newly added cases. In addition, a full sample regression and two sub-sample regressions are proposed to explain: (1) The changes in COVID-19 cases number are partly related to search variables related to treatments and medical resources, such as ventilators, hospitals, and masks, which correlate positively with the number of new cases. In contrast, regarding public health measures, social distancing, lockdown, stay-at-home, and self-isolation measures were negatively associated with the number of new cases in the US. (2) In mild states, which ranked one to twenty by the average daily new cases from least to most in 50 states, the query terms about public health measures (quarantine, lockdown, and self-isolation) have a significant negative correlation with the number of new cases. However, only the query terms about lockdown and self-isolation are also negatively associated with the number of new cases in serious states (states ranking 31 to 50). Furthermore, public health measures taken by the government during the COVID-19 outbreak are closely related to the situation of controlling the pandemic.

Diagnostic performance of mycological tests for invasive pulmonary aspergillosis in non-haematological patients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-ß-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases. METHODS AND ANALYSIS: Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2). ETHICS AND DISSEMINATION: This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal. PROSPERO REGISTRATION NUMBER: CRD42021241820.

Advances in nucleic acid amplification techniques (NAATs): COVID-19 point-of-care diagnostics as an example.

Achieving superhigh sensitivity is the ultimate goal for bio-detection in modern analytical science and life science. Among variable signal amplification strategies, nucleic acid amplification technologies are revolutionizing the field of bio-detection, providing greater possibilities in novel diagnosis achieving high efficiency, specificity, and cost-effectiveness. Nucleic acid amplification techniques (NAATs), such as Polymerase Chain Reaction (PCR), Rolling Circle Amplification (RCA), Loop-Mediated Isothermal Amplification (LAMP), Recombinase Polymerase Amplification (RPA), CRISPR-related amplification, and others are dominating methods employed in research and clinical settings. They each provide distinctively unique features that can offer desirable performance in terms of sensitivity, specificity, simplicity, stability, and cost. NAATs are in unmet demand in molecular diagnosis, especially in point-of-care scenario. This review will discuss the principles and recent advancements of each NAAT, respectively, revealing their strengths and challenges in achieving rapid and accurate bio-detection with a focus on point-of-care diagnosis. Furthermore, this review will explore the application of each of the technologies through the contemporary COVID-19 pandemic, analyzing their ability in point-of-care diagnosis of the COVID-19 with high sensitivity to emphasize significance of developing NAATs based methods in battling COVID-19. Finally, advantages and potentials of each NAAT in enhancements of sensitivity and specificity in bio-detection from bench side to the bedside will be discussed, aiming for full exploitation of capability of each NAAT. This review will provide novel aspects in the selection and combination of usages of various NAATs based on their distinctive characteristics and limitations. A possible advancing direction of future accurate POCT is also proposed.

Using Geotagged Social Media Data to Explore Sentiment Changes in Tourist Flow: A Spatiotemporal Analytical Framework

Understanding sentiment changes in tourist flow is critical in designing exciting experiences for tourists and promoting sustainable tourism development. This paper proposes a novel analytical framework to investigate the tourist sentiment changes between different attractions based on geotagged social media data. Our framework mainly focuses on visualizing the detailed sentiment changes of tourists and exploring the valuable spatiotemporal pattern of the sentiment changes in tourist flow. The tourists were first identified from social media users. Then, we accurately evaluated the tourist sentiment by constructing a Chinese sentiment dictionary, grammatical rule, and sentiment score. Based on the location information of social media data, we built and visualized the tourist flow network. Last, to further reveal the impact of attractions on the sentiment of tourist flow, the positive and negative sentiment profiles were generated by mining social media texts. We took Beijing, a famous tourist destination in China, as a case study. Our results revealed the following: (1) the temporal trend of tourist sentiment has seasonal characteristics and is significantly influenced by government control policies against COVID-19;(2) due to the impact of the attraction's historical background, some tourist flows with highly decreased sentiment strength are linked to attractions;(3) on the long journey to the attraction, the sentiment strength of tourists decreases;and (4) bad traffic conditions can significantly decrease tourist sentiment. This study highlights the methodological implications of visualizing sentiment changes during collective tourist movement and provides comprehensive insight into the spatiotemporal pattern of tourist sentiment. [ABSTRACT FROM AUTHOR] Copyright of ISPRS International Journal of Geo-Information is the property of MDPI Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nutritional practice in critically ill COVID-19 patients: A multicenter ambidirectional cohort study in Wuhan and Jingzhou.

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.