The physical frailty syndrome as a transition from homeostatic symphony to cacophony.

Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations.

Pandemic Exposure and Adolescent Anxiety: Roles of Negative Media Exposure and Negative Coping Styles (preprint)

The COVID-19 pandemic threatened people’s mental health, especially for adolescents, because their adjustment mechanisms of cognition and emotion are not perfect. They are more likely to have psychological health problems such as anxiety. The existing researches have carried out relevant discussions on this issue, indicating that excessive exposure to public health emergency events and negative coping styles are important factors causing psychological and behavioral problems such as anxiety. In this study, self-report questionnaires were distributed to 983 middle school students from Hubei province in China. This study focused on the role of negative media exposure and negative coping styles, so as to reveal the mechanism of adolescent anxiety during the pandemic. The results showed that pandemic exposure had a predicative effect on adolescent anxiety. The mechanism of this effect included the direct effect of pandemic exposure, the indirect effect of negative media exposure and negative coping styles.

A versatile integrated tube for rapid and visual SARS-CoV-2 detection

The coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide. Rapid and widespread testing is essential to promote early intervention and curb the ongoing COVID-19 pandemic. Current gold standard reverse transcription-polymerase chain reaction (RT-PCR) for detecting SARS-CoV-2 is restricted to professional laboratories and well-trained personnel, thus, limiting its widespread use in resource-limited conditions. To overcome these challenges, we developed a rapid and convenient assay using a versatile integrated tube for the rapid and visual detection of SARS-CoV-2. The reaction conditions of the method were optimized using SARS-CoV-2 RNA standards and the sensitivity and specificity were further determined. Finally, it was verified on clinical specimens. The assay was completed within 40 min, and the result was visible by the naked eye. The limits of detection (LODs) for the target ORF1ab and N genes were 50 copies/μl. No cross-reactivity was observed with the RNA standard samples of four respiratory viruses or clinical samples of common respiratory viral infections. Ninety SARS-CoV-2 positive and 30 SARS-CoV-2 negative patient specimens were analyzed. We compared these results to both prior and concurrent RT-PCR evaluations. As a result, the overall sensitivity and specificity for detection SARS-CoV-2 were 94.5 and 100.0%, respectively. Conclusion The integrated tube assay has the potential to provide a simple, specific, sensitive, one-pot, and single-step assay for SARS-CoV-2.

Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells (preprint)

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury, thus, it was further studied using biochemical, genetic and biophysical methods to ascertain mechanism of action via improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression and motion was required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that Intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.

Decreased Hospital-Acquired Respiratory Infections among elder Inpatients in General Hospital during the COVID-19 Pandemic (preprint)

Background In order to avoid nosocomial transmission of COVID-19, various prevention and control measures have been strictly implemented in medical institutions. These strict measures can probably reduce the incidence of hospital acquired respiratory infections. We conducted this study to assess changes in the prevalence of hospital acquired respiratory infections during a period of national attention to the prevention the COVID-19 pandemic.Methods We retrospectively analyzed the clinical data of patients from October to December 2019 and from October to December 2020. The diagnostic of hospital acquired respiratory infections was based on CDC/NHSN criteria. We compared the incidence and mortality rate of hospital acquired respiratory infections between these 2 periods. We also used multivariate logistics regression analysis for risk factors associated with mortality.Results In 2020, a total of 2921 patients’ data were surveyed, as compared with 2211 patients in 2019. Incidence of hospital acquired respiratory infections was lower in 2020 (2.9% vs. 4.7%, P = 0.001). In hospital mortality of patients with hospital acquired respiratory infections had no significant difference (38.4% vs. 30.5%, p = 0.252). Multivariate logistics regression analysis showed that severe pneumonia (RR = 28.235, 95%CI: 10.122, 78.759, p = 0.000), previous malignant tumor (RR = 4.599, 95%CI: 1.768, 11.963, p = 0.002) and cardiac injury (RR = 2.264, 95%CI: 0.935, 5.485, p = 0.07) were associated with an increased risk of mortality.Conclusions The incidence of hospital acquired respiratory tract infections was significantly decreased during COVID-19 period as a result of the adoption of infection prevention and control measures in medical institutions. Elder patients with severe pneumonia and previous malignant tumor were at high risk for death in hospital.

Air pollution and CO2 emission inventory of Chinese civil aviation airport

Based on the aircraft take-off and landing data of the Civil Aviation Administration of China,fleet configuration data,and the ICAO aircraft engine emission factor database from 2017 to 2020,the air pollution and CO2 emission inventory of the landing and take-off（LTO） cycle of high-resolution aircraft of civil aviation airport of China were developed from bottom to top.On this basis,the spatial and temporal distribution characteristics of air pollutants and CO2 on air pollution of China Civil Aviation Airport LTO cycle were explored.We analyzed the 3epidemics from 2000 to 2020（SARS in 2003,MERS in 2012,and COVID-19 in 2020）on airport air pollution and CO2 emissions.The results show that the emissions of NOx,CO,HC,SO2,PM,and CO2 in the LTO cycle of civil aviation airports in China in 2020 are 10.90,8.22,0.96,0.28,0.06,1360.27 million tons respectively;The emissions of HC,CO,SO2,and CO2 are the largest in the taxiing stage,accounting for 92.80%,91.56%,41.81% and 41.81% of the total emissions respectively.The emissions of NOx and PM are the largest in the climbing stage,accounting for 47.93% and 37.39% of the total emissions respectively;Air pollutants and CO2 emissions from China's Civil Aviation Airport LTO cycle showed an increasing trend over the past 2017～2019 years,and the total emissions in 2020 were reduced by 22.39% by COVID-19.The most concentrated emission area is the economically developed East region.In the 3 epidemics of the 2000～2020 years,COVID-19 has the most significant impact on the LTO emissions from China's civil aviation airport.

Sinophobia, misogyny, facism, and many more: A multi-ethnic approach to identifying anti-Asian racism in social media (preprint)

Anti-Asian hate/toxic/racial speech has recently increased, especially in response to the outbreak of COVID-19. However, heavy focus on the COVID-19 context and subsequent Sinophobia may have over-represented Chinese-attacking phenomena rather than offering insights applicable to pan-Asian communities. To fill this gap, this paper underscores a cross-ethnic contextual understanding by taking a multi-ethnic approach to identifying and describing anti-Asian racism expressed in Twitter. The study examines (1) cross-ethnicity difference (or similarity) of anti-Asian expressions; (2) temporal dynamics of cross-ethnicity difference/similarity; (3) topical contexts underlying anti-Asian tweets; and (4) comparison between Sinophobic tweets and pan-Asian or non-Chinese Asian targeting tweets. The study uses a 12 month-long large-scale tweets that contain ethnicity-indicative search keywords, from which anti-Asian tweets are identified using deep-learning models. Multiple correspondence analysis and topic modeling are employed to address research questions. Results show anti-Asian speeches are fragmented into several distinctive groups, and such groupings change dynamically in response to political, social, and cultural reality surrounding ethnic relations. Findings suggest that China is not a representative entity for pan-Asian ethnicity: Most of the times during the observed period, anti-China tweets are positioned distantly from generically mentioned anti-Asian tweets in the $n$-gram-based multidimensional space. Moreover, generic anti-Asian tweets show greater topical similarities to the combined set of tweets that attack other Asian ethnic groups than to the anti-China tweets. Pan-Asian tweets and China-specific tweets become semantically similar in the aftermath of the pandemic outbreak (from Feb. 2020 to Apr. 2020) yet only temporarily.

Global Trends in Nursing-Related Research on COVID-19: A Bibliometric Analysis

Background Coronavirus disease 2019 (COVID-19) has significantly impacted healthcare, especially the nursing field. This study aims to explore the current status and hot topics of nursing-related research on COVID-19 using bibliometric analysis. Methods Between 2019 and 2022, publications regarding nursing and COVID-19 were retrieved from the Web of Science core collection. We conducted an advanced search using the following search query string: TS = (“Novel coronavirus 2019” or “Coronavirus disease 2019” or “COVID 19” or “2019-nCOV” or “SARS-CoV-2” or “coronavirus-2”) and TS = (“nursing” or “nurse” or “nursing-care” or “midwife”). Bibliometric parameters were extracted, and Microsoft Excel 2010 and VOSviewer were utilized to identify the largest contributors, including prolific authors, institutions, countries, and journals. VOSviewer and CiteSpace were used to analyze the knowledge network, collaborative maps, hotspots, and trends in this field. Results A total of 5,267 papers were published between 2020 and 2022. The findings are as follows: the USA, China, and the UK are the top three prolific countries;the University of Toronto, the Harvard Medical School, the Johns Hopkins University, and the Huazhong University of Science & Technology are the top four most productive institutions;Gravenstein, Stefan, and White, Elizabeth M. from Brown University (USA) are the most prolific authors;The International Journal of Environmental Research and Public Health is the most productive journal;“COVID-19,” “SARS-CoV-2,” “nurse,” “mental health,” “nursing home,” “nursing education,” “telemedicine,” “vaccine-related issues” are the central topics in the past 2 years. Conclusion Nursing-related research on COVID-19 has gained considerable attention worldwide. In 2020, the major hot topics included “SARS-CoV-2,” “knowledge,” “information teaching,” “mental health,” “psychological problems,” and “nursing home.” In 2021 and 2022, researchers were also interested in topics such as “nursing students,” “telemedicine,” and “vaccine-related issues,” which require further investigation.

Effectiveness of Social Needs Screening and Interventions in Clinical Settings on Utilization, Cost, and Clinical Outcomes: A Systematic Review.

Objective: This systematic review examined and synthesized peer-reviewed research studies that reported the process of integrating social determinants of health (SDOH) or social needs screening into electronic health records (EHRs) and the intervention effects in the United States. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, a systematic search of Scopus, Web of Science Core Collection, MEDLINE, and Cochrane Central Register of Clinical Trials was performed. English language peer-reviewed studies that reported the process of integrating SDOH or social needs screening into EHRs within the U.S. health systems and published between January 2015 and December 2021 were included. The review focused on process measures, social needs changes, health outcomes, and health care cost and utilization. Results: In total, 28 studies were included, and half were randomized controlled trials. The majority of the studies targeted multiple SDOH domains. The interventions vary by the levels of intensity of their approaches and heterogeneities in outcome measures. Most studies (82%, n=23) reported the findings related to the process measures, and nearly half (43%, n=12) reported outcomes related to social needs. By contrast, only 39% (n=11) and 32% (n=9) of the studies reported health outcomes and impact on health care cost and utilization, respectively. Findings on patients' social needs change demonstrated improved access to resources. However, findings were mixed on intervention effects on health and health care cost and utilization. We also identified gaps in implementation challenges to be overcome. Conclusion: Our review supports the current policy efforts to increase U.S. health systems' investment toward directly addressing SDOH. While effective interventions can be more complex or resource intensive than an online referral, health care organizations hoping to achieve health equity and improve population health must commit the effort and investment required to achieve this goal.

Evolution analysis of online topics based on ‘word-topic’ coupling network

Analyzing topic evolution is an effective way to monitor the overview of topic spreading. Existing methods have focused either on the intensity evolution of topics along a timeline or the topic evolution path of technical literature. In this paper, we aim to study topic evolution from a micro perspective, which not only captures the topic timeline but also reveals the topic status and the directed evolutionary path among topics. Firstly, we construct a word network by co-occurrence relationship between feature words. Secondly, Latent Dirichlet allocation (LDA) model is used to automatically extract topics and capture the mapping relationship between words and topics, and then a ‘word-topic’ coupling network is built. Thirdly, based on the ‘word-topic’ coupling network, we describe the topic intensity evolution over time and measure topic status considering the contribution of feature words to a topic. The concept of topic drifting probability is proposed to identify the evolutionary path. Experimental results conducted on two real-world data sets of “COVID-19” demonstrate the effectiveness of our proposed method.

COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of coronavirus disease 2019 (COVID-19), binds via ACE2 receptors, highly expressed in ciliated cells of the nasal epithelium. Micro-optical coherence tomography (OCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-m resolution, enabling real time visualization and quantification of epithelial anatomy, ciliary motion, and mucus transport. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as reduced ciliated cell function and mucociliary abnormalities, features readily visualized by OCT. Symptomatic outpatients with SARS-CoV-2 aged [≥] 18 years were recruited within 14 days of symptom onset. Data was interpreted for subjects with COVID-19 (n=13) in comparison to healthy controls (n=8). Significant reduction in functional cilia, diminished ciliary beat frequency, and abnormal ciliary activity were evident. Other abnormalities included denuded epithelium, presence of mucus rafts, and increased inflammatory cells. Our results indicate that subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa underscoring the importance of mucociliary health in viral illness and disease transmission. Ciliary imaging enables investigation of early pathogenic mechanisms of COVID-19 and may be useful for evaluating disease progression and therapeutic response.

The effect of the systemic immune-inflammation index on conversion time of virus nucleic acid turning negative in COVID-19 patients

Objective: To investigate the effect of the systemic immune-inflammation index(SII) on the conversion time of virus nucleic acid turning negative in patients with coronavirus disease 2019(COVID-19).

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes (preprint)

Introduction: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. Methods: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher exact tests, Spearman correlations and linear regression models. Results: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term ([≥]37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. Discussion: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

Stressful events induce long-term gut microbiota dysbiosis and associated post-traumatic stress symptoms in healthcare workers fighting against COVID-19.

OBJECTIVE: The microbiota-gut-brain axis is a key pathway perturbed by prolonged stressors to produce brain and behavioral disorders. Frontline healthcare workers (FHWs) fighting against COVID-19 typically experience stressful event sequences and manifest some mental symptoms; however, the role of gut microbiota in such stress-induced mental problems remains unclear. We investigated the association between the psychological stress of FHW and gut microbiota. METHODS: We used full-length 16S rRNA gene sequencing to characterize the longitudinal changes in gut microbiota and investigated the impact of microbial changes on FHWs' mental status. RESULTS: Stressful events induced significant depression, anxiety, and stress in FHWs and disrupted the gut microbiome; gut dysbiosis persisted for at least half a year. Different microbes followed discrete trajectories during the half-year of follow-up. Microbes associated with mental health were mainly Faecalibacterium spp. and [Eubacterium] eligens group spp. with anti-inflammatory effects. Of note, the prediction model indicated that low abundance of [Eubacterium] hallii group uncultured bacterium and high abundance of Bacteroides eggerthii at Day 0 (immediately after the two-month frontline work) were significant determinants of the reappearance of post-traumatic stress symptoms in FHWs. LIMITATIONS: The lack of metabolomic evidence and animal experiments result in the unclear mechanism of gut dysbiosis-related stress symptoms. CONCLUSION: The stressful event sequences of fighting against COVID-19 induce characteristic longitudinal changes in gut microbiota, which underlies dynamic mental state changes.

Natural outbreaks and molecular characteristics of Streptococcus agalactiae infection in farmed American bullfrog (Rana catesbeiana)

Between June and September 2019, a disease outbreak resulted in high mortality rates on four American bullfrog farms in Wenchang, Hainan Province, China. The main clinical signs included congestion and hemorrhage of the skin on the abdomen and hind limbs, ascites, hepatomegaly and internal organ hyperemia. Gram-positive cocci were isolated from the primary organs and tissues of 149 of 160 collected dead and moribund bullfrogs. The isolates were identified as Streptococcus agalactiae based on their morphology, biochemical characteristics and 16S rDNA sequencing analysis. S. agalactiae was isolated from diseased bullfrogs from all farms, and strain WH914 was selected for experimental infection of bullfrogs. Similar lesions were observed in the experimental bullfrogs, and 17.0%, 33.3% and 100.0% mortality occurred 14 days after administering 8.3 × 104 CFU/ml, 8.3 × 106 CFU/ml and 8.3 × 108 CFU/ml of the bacteria, respectively. Molecular serotyping of the capsular polysaccharide gene clusters revealed that the S. agalactiae isolates were serotype Ib. The sequence type (ST) of 30 isolates randomly selected from each bullfrog farm was determined by multilocus sequence typing as ST261. Virulence gene profiles for 14 virulence-related genes were constructed via multiplex PCR. All strains contained pavA, sip, iagA, cfb, hylB, bibA, cspA and fbsA but lacked cylE, bac, imb, scpB, rib and bca. S. agalactiae serotype Ib ST261 was isolated from sick or deceased farmed bullfrogs and is recognized as a pathogen of bullfrogs. Natural infections of S. agalactiae serotype Ib ST261 have not been previously reported in American bullfrogs. • Streptococcus agalactiae was isolated from diseased American bullfrog. • Histological characteristics were necrotizing hepatitis, splenitis and nephritis. • S. agalactiae isolates are serotype Ib and sequence type ST261. • S. agalactiae risks should be warned in bullfrogs aquaculture. [ FROM AUTHOR] Copyright of Aquaculture is the property of Elsevier B.V. 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 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 . (Copyright applies to all s.)

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation (preprint)

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a novel mechanism by which the SARS-CoV-2 virus co-opts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-{beta}. We reveal that the SARS-CoV-2 encoded Non-Structural Protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-{beta} production, leading to reduced viral infection. Our findings reveal a new target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.

The relationship between anti-epidemic mentality and post-traumatic stress disorder in medical college students during the COVID-19 pandemic

Objective: To explore the relationship between an anti-epidemic mentality and post-traumatic stress disorder (PTSD) among college students during the corona virus disease 2019(COVID-19) pandemic, and to provide a scientific basis for the prevention of PTSD when college students experience sudden crisis events in the future.

Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection (preprint)

Substantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an in vivo model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways. Corresponding to progressive weight loss up to 7 days post- infection (dpi), viral detection and histopathological analysis in both the trachea and lung revealed steadily descending infection from the upper airways, as the main target of viral invasion, to lower airways and parenchymal lung, which are likely injured through indirect mechanisms. SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 dpi, largely due to diminished motile ciliation coverage, but not airway surface liquid depth, periciliary liquid depth, or cilia beat frequency of residual motile cilia. Further analysis indicated that the fewer motile cilia combined with abnormal ciliary motion of residual cilia contributed to the delayed MCT. The time course of physiological, virological, and pathological progression suggest that functional deficits of the MCT apparatus predispose to COVID-19 pathogenesis by extending viral retention and may be a risk factor for secondary infection. As a consequence, therapies directed towards the MCT apparatus deserve further investigation as a treatment modality.