Creutzfeldt-Jakob Disease with Initial Typical Parkinsonism Precipitated by COVID-19? A Case Report (preprint)

Background Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease caused by the accumulation of PrPSc. While COVID-19-induced sporadic CJD (sCJD) with parkinsonism as the initial symptom is extremely uncommon, this report aims to raise awareness of sCJD cases that present with parkinsonism that are not associated with genetic mutations or pathological α-synuclein (α-Syn) accumulation. Case presentation This report presents the case of a 72-year-old man with probable sporadic Creutzfeldt-Jakob disease (sCJD) who initially showed symptoms of parkinsonism, which worsened rapidly after contracting COVID-19. Despite a history of responsive tremor and bradykinesia, his condition deteriorated following the viral infection, leading to rapid consciousness decline and diffuse myoclonus. Diagnostic tests, including brain MRI, cerebrospinal fluid analysis, and EEG, pointed towards prion disease. PrPSc, a marker for CJD, was detected in both the cerebrospinal fluid and skin samples using RT-QuIC, further confirming the diagnosis. Notably, skin analysis revealed PrPSc but no pathological α-synuclein deposits, ruling out typical Parkinson's disease.  Conclussion This case underscores the importance of considering sCJD in patients with parkinsonism, especially if they experience sudden neuropsychiatric symptoms, especially if they do not exhibit pathological α-Syn accumulation or have genetic mutations.

Acute stress reaction, depression anxiety stress, and job withdrawal behavior in non-frontline pediatric nurses during the pandemic: a cross-sectional study.

Backgrounds: The COVID-19 pandemic has brought an unprecedented healthy crisis to people worldwide. It is crucial to assess the psychological status of non-frontline nurses. More attention to the mental and physical health of non-frontline nurses during a public health emergency is necessary for a full understanding of the implications. Therefore, this study aims to investigate the factors that influence the acute stress reaction of non-frontline pediatric nurses during the COVID-19 pandemic. Methods: This study aimed to explore factors associated with acute stress reactions of non-frontline pediatric nurses in Hunan province during the COVID-19 pandemic. This was a cross-sectional design. Five hundred eighteen pediatric nurses from Hunan province, China, completed the Stanford Acute Stress Reaction Questionnaire (SASRQ), Depression Anxiety Stress Scales-21 (DASS-21), and Job Withdrawal Behavior Scales (JWB). Multiple linear regression analyses and Pearson's correlation were used to analyze the results. Results: The mean scores of DASS-21, JWB, SASRQ were 1.443 ± 0.500, 1.601 ± 0.544, and 1.858 ± 0.805, respectively. Stress, anxiety, depression (three sub-dimensions of DASS-21), JWB, monthly income and department were the major predictive factors for SASRQ (Adjusted R2 = 0.579, p < 0.001). Pearson's correlation showed that the mean score of SASRQ was positively correlated with JWB, DASS-21, and all its dimensions (p < 0.01). Conclusion: The study indicated that the SASRQ was greater with higher levels of DASS-21 and JWB. It revealed an acute stress reaction in non-frontline pediatric nurses and recommends more focus on the factors influencing the SASRQ.

An Integrated Approach with CLFPR-Based ANP and Fuzzy TOPSIS for Evaluating Business Performance of Rural Homestays: Study from China

Given the high importance of the performance of rural homestays to the local economy, this study aims to fill the gap in homestay performance research and make rural homestays more competitive and sustainable after the coronavirus disease epidemic (COVID-19). Integrating a consistent linguistic fuzzy preference relations-based analytic network process (CLFPR-based ANP) and a fuzzy technique for order performance by similarity to ideal solution (TOPSIS), this study constructs a comprehensive evaluation model of the performance of rural homestays and empirically analyzes homestay performance in Zhejiang. The results show the following: (1) Among the criteria's weights by CLFPR-based ANP, homestay operation and management, service quality, and homestay geist and community co-prosperity should be given much more attention;the importance of factors regarding the environment and building of rural homestays is gradually weakening. (2) In light of ranking alternatives based on performance evaluation by fuzzy TOPSIS, the homestay with the optimal performance has been found, which practitioners can use as a benchmark. Therefore, the priorities of these criteria further deepen the understanding of the performance of rural homestays and underline the development direction for practitioners. Simultaneously, in terms of feasibility and reliability, the integrated approach comprises a beneficial attempt and becomes an effective evaluation tool for practitioners to improve effectiveness.

How culture orientation influences the COVID-19 pandemic: An empirical analysis

Purpose This study aims to investigate the mediational path of the influence of cultural orientation on the COVID-19 pandemic outcome at the national level and find out whether some culture-related factors can have a moderating effect on the influence of culture. Methodology Cultural dimension theory of Hofstede is used to quantify the degree of each dimension of culture orientation. The cross-section regression model is adopted to test if culture orientations affect the pandemic outcome, controlling for democracy, economy, education, population, age, and time. Then, a mediational analysis is conducted to examine if policy response is the mediator that culture makes an impact on the pandemic outcome. Finally, a moderation analysis is carried out to determine how each control variable has moderated the influence. Findings The cross-section regression results showed that culture orientation influences the outcome of the COVID-19 pandemic at the 99% confidence level and that among the six cultural dimensions, collectivism-individualism has the most significant impact. It has also been found that policy response is the mediator of cultural influence, and culture-related factors can moderate the influence. Contribution The contribution of this research lies in developing the assertion that culture influences pandemic outcomes. Our findings indicate that collectivism-individualism culture orientation affects the effectiveness of epidemic controls the most among the six culture dimensions. Additionally, our research is the first to study the mediating effect of policy responses and the moderating effect of culture-related factors on the influence of cultural orientation on the pandemic outcome.

Mechanism of Huoxiang Zhengqi oral liquid in the treatment of COVID-19 based on biological information technology

Objective: To explore the network regulation mechanism of Huoxiang Zhengqi Oral Liquid(HXZQ) in the treatment of coronavirus disease 19 (COVID-19).

Exploring the Effects of Different Bacteria Additives on Fermentation Quality, Microbial Community and In Vitro Gas Production of Forage Oat Silage

Simple SummaryForage oat is an important feed resource in the world. Few studies on the application of different bacterial additives in forage oat silage have been found, which limits the utilization and promotion of oat silage in animal husbandry. In this study, we compared the fermentation quality and in vitro gas production of oat silage treated with four additives (Lactiplantibacillus plantarum F1,LP;Lacticaseibacillus rhamnosus XJJ01, LR;Lacticaseibacillus paracasei XJJ02, LC;and Propionibacterium acidipropionici 1.1161, PP). The results show that compared to the CK group (without additives), the LR group had a higher dry matter content, while the LP group showed an improvement in fermentation quality. At the same time, the bacterial community in the LR group was also different from that in other groups. The treatments of PP and LC had no significant effects on fermentation quality, but the in vitro gas production was significantly reduced in the treated oat silage. These results could help us to optimize the utilization of forage oat silage in balanced ruminant diets.Bacterial inoculants are considered as a good choice for successful ensiling, playing a key role in improving the silage quality. However, the potential of different bacteria, especially the propionic acid bacteria, in forage oat ensiling is yet to be explored. Therefore, the purpose of this study was to investigate the regulation effects of different bacterial additives on the fermentation quality of forage oat silage. Four additives (Lactiplantibacillus plantarum F1, LP;Lacticaseibacillus 0rhamnosus XJJ01, LR;Lacticaseibacillus paracasei XJJ02, LC;and Propionibacterium acidipropionici 1.1161, PP;without additives, CK) were inoculated in forage oat silage, and the fermentation quality and organic compounds were determined after 60 days of ensiling. Notably, LR showed higher dry matter preservation compared to other additives and CK. In addition, LP and LR showed strong lactic acid synthesis capacity, resulting in lower pH compared to other additives and CK. The treatments of PP and LC increased the bacterial diversity in silage, while the bacterial community in the LR group was different from that in other groups. In addition, the PP- and LC-treated oat silage showed significantly lower total in vitro gas production and a lower methane content. These results suggest that LP is more favorable for producing high-quality oat silage than LR, LC, or PP. Both the PP- and LC- treated oat silage may reduce rumen greenhouse gas emissions.

Multi-Omic Profiling of Plasma Identify Biomarkers and Pathogenesis of COVID-19 in Children (preprint)

Background: Children usually develop less severe disease responding to COVID-19 than adults. However, little is known about the detailed mechanism and pathogenesis of children with COVID-19 (CC), and its difference to adults with COVID-19 (AC).Methods: We conducted a plasma proteomic and metabolomic profiling, using the blood samples of 30 children including 18 CC cases and 12 healthy children (HC). By comparing the multi-omic data of AC, standard statistical tests were used to identify differentially expressed proteins (DEPs) and metabolites (DEMs) exclusively altered in CC. Enrichment analyses were conducted to identify biological processes/pathways specifically enriched in CC. To identify potential CC-specific biomarkers, we developed a new machine learning-based method named inference of biomarker combinations with minimal bias (iBM). Further experiments were conducted to validate the predicted metabolic markers.Findings: By quantifying 757 proteins and 1174 metabolites, we identified 44 DEPs and 249 DEMs exclusively altered in CC. Enrichment analyses demonstrated that in CC both deleterious immune response/inflammation processes and protective anti-inflammatory processes were strongly induced in the proteomic level, whereas protective anabolism-related processes were enriched in the metabolomic level. Using iBM, we prioritized two CC-specific biomarker combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish CC from HC or AC. Further experiments showed that the identified metabolites not only inhibited the expression of pro-inflammatory factors, but also suppressed coronaviral replication, implying that these factors played key roles in protecting pediatric patients from both viral infection and infection-induced inflammation.Interpretation: The finding of a strong antagonism of deleterious and protective effects provided new insights on the mechanism and pathogenesis of CC cases that mostly undergo mild symptoms. The identified CC-specific biomarkers could serve as candidate drug targets or therapeutic agents of COVID-19.Funding Statement: This work was supported by the Strategic Priority Research Program of CAS (XDB29010300 to X.Z.), the National Science and Technology Major Project (2018ZX10101004 to X.Z.), National Natural Science Foundation of China (81873964 to Y.Q., 31930021, 31970633 and 34671360 to Y.X., and 31670161 to X.Z.), Grant from the CAS Youth Innovation Promotion Association (2020332 to Y.Q.), the program for HUST Academic Frontier Youth Team (Y.X.).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: All work performed in this study was approved by the Guangzhou Women and Children's Medical Center Ethics Committee and Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2 (preprint)

Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal inflammatory responses in the circulation and at the maternal-fetal interface, the latter being governed by T cells and macrophages. SARS-CoV-2 infection during pregnancy was also associated with a cytokine response in the fetal circulation (i.e. umbilical cord blood) without compromising the cellular immune repertoire. Moreover, SARS-CoV-2 infection neither altered fetal cellular immune responses in the placenta nor induced elevated cord blood levels of IgM. Importantly, SARS-CoV-2 was not detected in the placental tissues, nor was the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and further emphasizes the rarity of placental infection.

Multi-Omic Profiling of Plasma Identify Biomarkers and Pathogenesis of COVID-19 in Children (preprint)

Although children usually develop less severe disease responding to COVID-19 than adults, little is known about the pathogenesis of COVID-19 in children. Herein, we conducted the plasma proteomic and metabolomic profiling of a cohort of COVID-19 pediatric patients with mild symptoms. Our data show that numerous proteins and metabolites involved in immune as well as anti-inflammatory processes were up-regulated on a larger scale in children than in adults. By developing a machine learning-based pipeline, we prioritized two sets of biomarker combinations, and identified 5 proteins and 5 metabolites as potential children-specific COVID-19 biomarkers. Further study showed that these identified metabolites not only inhibited the expression of pro-inflammatory factors, but also suppressed coronaviral replication, implying that these factors played key roles in protecting pediatric patients from both viral infection and infection-induced inflammation. Together, our study uncovered a protective mechanism responding to COVID-19 in children, and sheds light on potential therapies. Teaser Anti-inflammatory metabolites were highly elevated in the plasma of COVID-19 pediatric patients with mild symptoms.

Multi-attribute group decision-making for online education live platform selection based on linguistic intuitionistic cubic fuzzy aggregation operators

The purpose of this study is to propose a multi-attribute group decision-making (MAGDM) method for online education live platform selection based on proposed novel aggregation operators (AOs) under linguistic intuitionistic cubic fuzzy set (LICFS). First, the Archimedean copula and co-copula are extended to handle linguistic intuitionistic cubic fuzzy information (LICFI) and the operational law of linguistic intuitionistic cubic fuzzy variables (LICFVs) based on extended copula (EC) and extended co-copula (ECC) are given. In addition, linguistic intuitionistic cubic fuzzy copula weighted average (LICFCWA) operator and linguistic intuitionistic cubic fuzzy copula weighted geometric (LICFCWG) operator are proposed based on EC and ECC under LICFI;meanwhile, some special forms of LICFCWA and LICFCWG have been obtained by different types generators of ECs and ECCs. Third, a novel MAGDM approach based on proposed LICFCWA (LICFCWG) is constructed to solve the selection problem of the online education live platform in the period of the COVID-19, and a detailed parameter analysis was carried out. Fourthly, LICFS will degenerate into linguistic intuitionistic fuzzy set and intuitionistic cubic fuzzy set, respectively, in different cases. Finally, some comparisons are carried out with other existing proposed MAGDM approaches. By comparing different types of experiments, the effectiveness and flexibility of the proposed approach are also showed.

Vulnerability of Young Children with COVID-19: Impacts of ACE2 Expression Patterns and Lung Progenitor Cells on Infants (preprint)

Background: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin- converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 25, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children’s lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Findings: It revealed that infants (<1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (>1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children’s lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants’ lungs. The ACE2+ SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Interpretation: Infants (<1 yrs.-old) with COVID-19 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from COVID-19 infection. Funding: National Natural Science Grant of China (No 31571407; 31970910); Hong Kong Health and Medical Research Fund (HMRF) (No:06172956), and Stem Cell and Regenerative Medicine Fund (Guangzhou Women and Children's Medical Centre, Grant No:5001-4001010)Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the respective Institutional Review Board. Written informed consent was obtained from patients and/or guardians before data collected.

Community nursing services during the COVID-19 pandemic: the Singapore experience.

Community nurses in Singapore support vulnerable older persons with chronic health condition(s). In the situation of scaled-down community health and social services during the COVID-19 outbreak, the community nursing team adopted measures for pandemic preparedness. This report is to share the Singapore General Hospital community nursing experience, preparation and transforming efforts during the pandemic. Team segregation, active screening and triage before visits and other precautionary measures were executed to minimise the risk of exposure to COVID-19. There was a shift from face-to-face to teleconsultation to meet the requirement of safe social-distancing. Community nursing teams continued to play an active role in supporting older persons during the pandemic, despite the challenges. Moving to the lockdown phase ('circuit breaker'), teleconsultation, virtual meetings and integrated partnerships were essential to ensure healthcare accessibility and continuity of care. The experience gleaned was valuable to advance future community nursing services in the evolving healthcare landscape. Structured teleconsultation and technology advancement are useful to complement the service.

Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants (preprint)

BackgroundIn response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown, partly due to the difficulty of obtaining unbiased genome coverage of SARS-CoV-2 directly from clinical samples. MethodsEighteen time series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method with different rounds of hybridization. ResultsBy examining the sequencing depth, genome coverage, and allele frequency change, we demonstrated the impeccable performance of the hybrid capture method in samples with Ct value < 34, as well as significant improvement comparing to direct metatranscriptomic sequencing in samples with lower viral loads. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Meanwhile, we also found that the same mutation showed different frequency changes in different individuals, indicating a strong random drift. Moreover, the evolving of the viral genome demonstrated that the virus was still viable in the gastrointestinal tract during the convalescent period. ConclusionsThe hybrid capture method enables reliable analyses of inter- and intra-host variants of SARS-CoV-2 genome, which changed dramatically in the gastrointestinal tract; its clinical relevance warrants further investigation.

Comparison of clinical features on admission between coronavirus disease 2019 and influenza A among children: a retrospective study in China (preprint)

Background: Coronavirus disease 2019 (COVID-19) share similar symptoms with influenza A (IA), but it is more worthwhile to understand the disparities of the two infections regarding their clinical characteristics on admission. Methods: A total of 71 age-matched pediatric IA and COVID-19 patient pairs were formed and their clinical data on admission were compared. Results: Fever, cough, nasal congestion and nausea/vomiting were the most common symptoms on admission for both infections but occurred less often in COVID-19. The IA patients were more likely to have lower-than-normal levels of lymphocyte count and percentage and to have higher-than-normal levels of activated partial thromboplastin time, prothrombin time, serum C-reactive protein, and serum procalcitonin, while the COVID-19 patients had higher odds of having lower-than-normal levels of neutrophil count and percentage. Conclusion: This study suggests that influenza A is more symptomatic than COVID-19 for children and might be an overall more severe infection at the time of admission.

Does the human placenta express the canonical cell entry mediators for SARS-CoV-2? (preprint)

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 3.8 million people, including pregnant women. To date, no consistent evidence of vertical transmission for SARS-CoV-2 exists. This new coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. Herein, building upon our previous single cell study of the placenta (Pique-Regi, 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy as well as in third-trimester chorioamniotic membranes. We report that co-transcription of ACE2 and TMPRSS2 is negligible, thus not a likely path of vertical transmission for SARS-CoV-2 at any stage of pregnancy. In contrast, receptors for Zika virus and cytomegalovirus which cause congenital infections are highly expressed by placental cell types. These data suggest that SARS-CoV-2 is unlikely to infect the human placenta through the canonical cell entry mediators; yet, other interacting proteins could still play a role in the viral infection.

Epidemiological and clinical characteristics of imported cases with COVID-19 infection: a multicentre study (preprint)

Objective: Numerous cases of COVID-19 were confirmed in the world in succession. We reported the epidemiological and clinical features of 478 confirmed cases from a multicentre study outside of Wuhan, China. Methods : We collected patients who were transferred by Emergency Medical Service to the designated hospitals in four major cities including Beijing, Chongqing, Jinan and Nanning in China. We compared the characteristics between imported and indigenous cases, and calculated the fatality, and the rate of severe cases, mild and asymptomatic cases to generate the pyramid of COVID-19 infection. Results : The mean age of patients was 46.9 years old and 49.8% were male. The most common symptoms at the onset of illness were fever (69.7% ), cough (47.5%), fatigue (24.5%), dyspnea (8.4%) and headache (7.9%). In the study, most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. During the early stage, the imported cases were dominant, which declined from Feb 1, when the indigenous cases rise sharply. Compared with the indigenous cases, the imported cases were significantly distinct concerning gender composition (P=0.002), classification of severity (P=0.006). Conclusions : On the basis of this study, we suggest that preventing import from outside and controlling spread inside should be a basic principle for resisting COVID-19 infection. If not, the region or area will face chaos.

Impact of Short Food Videos on the Tourist Destination Image—Take Chengdu as an Example

Taking Chengdu as an example, based on the destination image theory and employing the content analysis methodology, this paper conducts data mining on the online comment texts of TikTok short food videos, and analyzes the impact of short food videos on the destination image (cognitive image, affective image and conative image). The results show that: (1) in terms of cognitive image, short food videos have increased potential tourists’ attention to the destination image, especially their attention to the flavor characteristics of food in the destination and the local social environment;(2) in terms of affective image, the comments of short food videos are mainly neutral and positive, and the contents about the flavor characteristics of food and the local social environment are more likely to affect the affective image of the destination;and (3) in terms of conative image, the appearance description of food in short food videos brings about an obvious effect of intention, and it also creates the demand to travel together and obtain information. This paper is inspiring for city managers and tourism marketers to use TikTok short videos to establish and disseminate food-based city brands and destination images.