Research progress on distribution and exposure risk of microbial aerosols in animal houses.

Environmental aerosols in animal houses are closely related to the productive performance and health level of animals living in the houses. Preferable housing environments can improve animal welfare and production efficiency, so it is necessary to monitor and study these environments. In recent years, there have been many large-scale outbreaks of respiratory diseases related to biological aerosols, especially the novel coronavirus that has been sweeping the world. This has attracted much attention to the mode of aerosol transmission. With the rapid development of large-scale and intensive breeding, microbial aerosols have gradually become the main factor of environmental pollution in animal houses. They not only lead to a large-scale outbreak of infectious diseases, but they also have a certain impact on the health of animals and employees in the houses and increase the difficulty of prevention and control of animal-borne diseases. This paper reviews the distribution, harm, and control measures of microbial aerosols in animal house environments in order to improve people's understanding of them.

Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation.

In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived N-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.

Revival Duration and Determinants of ASEAN Machinery Trade During COVID-19 Pandemic and the Global Financial Crisis

This study performs survival analysis to evaluate duration of revived and new machinery import and the hazard ratios (HRs) of covariates related to the global financial crisis (GFC) and COVID-19 pandemic in the Association of Southeast Asian Nations (ASEAN). The results indicate that large tariff margins decreased the possibility of disruption (HR: 0.8024) to Japanese import from ASEAN countries after revived during the COVID-19 pandemic and increased the possibility of disruption (HR: 1.0338) to Chinese import from ASEAN countries of new import during the GFC.

Case report: One pediatric liver-transplant recipient with SARS-CoV-2 infection suffering unexplained mixed acidosis.

Background: The management of LT patients during COVID-19 pandemic is important. Immunosuppressants (IS) are key therapy agents after liver transplant. Different ISs have different side effects. Calcineurin inhibitor (CNI) may lead to metabolic acidosis while mycophenolate mofetil (MMF) showed rare nephrotoxicity. We report a post-liver transplant girl who was infected with SARS-CoV-2, developing a severe mixed acidosis 3 months after the transplantation. Her acidosis was improved after withdrawing of MMF, leading the suspicion that acidosis maybe a rare side effect of MMF. Case presentation: A girl was admitted to our hospital due to SARS-CoV-2 infection, 3 months before admission the patient received LT due to Niemann-Pick disease (NPD). During hospitalization, blood gas analysis showed severe mixed acidosis. To relieve mixed acidosis, the patient was given oral rehydration salt and liquid replacement therapy. Considering that immunosuppressants may cause metabolic acidosis, dose of CsA was decreased and MMF was discontinued. Results: However, liquid replacement therapy and decreased CsA dose cannot improve the condition. As an attempt, MMF was discontinued, and 3 days later, the girl's acidosis was relieved, the latest blood gas analysis was normal with the original dose of CsA and no use of MMF or other IS. In addition, we used Naranjo Scale to see if adverse drug reactions (ADRs) existed. The final score was 6 which means MMF contributes to acidosis probably. Conclusion: The girl's mixed acidosis cannot be explained by Niemann-Pick disease and SARS-CoV-2 infection. CNIs could cause metabolic acidosis but declining the dose of CsA didn't improve her acidosis while withdrawing MMF showed a good effect. Together with the Naranjo Scale result, we suspect that acidosis maybe a rare side effect of MMF.

Classification of COVID-19 from community-acquired pneumonia: Boosting the performance with capsule network and maximum intensity projection image of CT scans.

BACKGROUND: The coronavirus disease 2019 (COVID-19) and community-acquired pneumonia (CAP) present a high degree of similarity in chest computed tomography (CT) images. Therefore, a procedure for accurately and automatically distinguishing between them is crucial. METHODS: A deep learning method for distinguishing COVID-19 from CAP is developed using maximum intensity projection (MIP) images from CT scans. LinkNet is employed for lung segmentation of chest CT images. MIP images are produced by superposing the maximum gray of intrapulmonary CT values. The MIP images are input into a capsule network for patient-level pred iction and diagnosis of COVID-19. The network is trained using 333 CT scans (168 COVID-19/165 CAP) and validated on three external datasets containing 3581 CT scans (2110 COVID-19/1471 CAP). RESULTS: LinkNet achieves the highest Dice coefficient of 0.983 for lung segmentation. For the classification of COVID-19 and CAP, the capsule network with the DenseNet-121 feature extractor outperforms ResNet-50 and Inception-V3, achieving an accuracy of 0.970 on the training dataset. Without MIP or the capsule network, the accuracy decreases to 0.857 and 0.818, respectively. Accuracy scores of 0.961, 0.997, and 0.949 are achieved on the external validation datasets. The proposed method has higher or comparable sensitivity compared with ten state-of-the-art methods. CONCLUSIONS: The proposed method illustrates the feasibility of applying MIP images from CT scans to distinguish COVID-19 from CAP using capsule networks. MIP images provide conspicuous benefits when exploiting deep learning to detect COVID-19 lesions from CT scans and the capsule network improves COVID-19 diagnosis.

Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant.

BACKGROUND: Gut microbiota alterations have been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). This study aimed to explore gut microbiota changes in a prospective cohort of COVID-19 children and their asymptomatic caregivers infected with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant. METHODS: A total of 186 participants, including 59 COVID-19 children, 50 asymptomatic adult caregivers, 52 healthy children (HC), and 25 healthy adults (HA), were recruited between 15 April and 31 May 2022. The gut microbiota composition was determined by 16S rRNA gene sequencing in fecal samples collected from the participants. Gut microbiota functional profiling was performed by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. RESULTS: The gut microbiota analysis of beta diversity revealed that the fecal microbial community of COVID-19 children remained far distantly related to HC. The relative abundances of the phyla Actinobacteria and Firmicutes were decreased, whereas Bacteroidetes, Proteobacteria, and Verrucomicrobiota were increased in COVID-19 children. Feces from COVID-19 children exhibited notably lower abundances of the genera Blautia, Bifidobacterium, Fusicatenibacter, Streptococcus, and Romboutsia and higher abundances of the genera Prevotella, Lachnoclostridium, Escherichia-Shigella, and Bacteroides than those from HC. The enterotype distributions of COVID-19 children were characterized by a high prevalence of enterotype Bacteroides. Similar changes in gut microbiota compositions were observed in asymptomatic caregivers. Furthermore, the microbial metabolic activities of KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (cluster of orthologous groups of proteins) pathways were perturbed in feces from subjects infected with the SARS-CoV-2 Omicron variant. CONCLUSION: Our data reveal altered gut microbiota compositions in both COVID-19 children and their asymptomatic caregivers infected with the SARS-CoV-2 Omicron variant, which further implicates the critical role of gut microbiota in COVID-19 pathogenesis.

Research progress on distribution and exposure risk of microbial aerosols in animal houses

Environmental aerosols in animal houses are closely related to the productive performance and health level of animals living in the houses. Preferable housing environments can improve animal welfare and production efficiency, so it is necessary to monitor and study these environments. In recent years, there have been many large-scale outbreaks of respiratory diseases related to biological aerosols, especially the novel coronavirus that has been sweeping the world. This has attracted much attention to the mode of aerosol transmission. With the rapid development of large-scale and intensive breeding, microbial aerosols have gradually become the main factor of environmental pollution in animal houses. They not only lead to a large-scale outbreak of infectious diseases, but they also have a certain impact on the health of animals and employees in the houses and increase the difficulty of prevention and control of animal-borne diseases. This paper reviews the distribution, harm, and control measures of microbial aerosols in animal house environments in order to improve people's understanding of them.

Chemical Constituents, Quantitative Analysis, Anti-SARS-CoV-2 and Antioxidant Activities of Herbal Formula 'Ping An Fang Yu Yin'

COVID-19 is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The herbal formula, Ping An Fang Yu Yin (PAFYY), has been used to prevent respiratory viral infections for many years. This study aims to evaluate the effect of PAFYY on SARS-CoV-2 infection, oxidative stress, and inflammation via in vitro, investigate the chemical composition by full constituent quantitative analysis, and verify its anti-viral potential against SARS-CoV-2 using in silico. In this study, a total of eleven compounds, twenty amino acids, saccharide compositions, and trace elements were found and quantitatively determined by chromatographic techniques. PAFYY displayed free radical scavenging activity (DPPH, SC50: 1.24 ±0.09 mg/mL), SOD activity (68.71 ±1.28%), inhibition of lipoxygenase activity (75.96 ±7.64 mg/mL) and interfered the interaction of SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (48.04 ±3.18%). Furthermore, in-silico analysis results supported that liquiritin, 3,5-dicaffeoylquinic acid, and luteolin-7-O-glucoside with the highest affinity between SARS-CoV-2 RBD and human angiotensin-converting enzyme II (hACE2) receptor. Our findings suggest that PAFYY has the potential for anti-SARS-CoV-2 infection, anti-oxidation stress, and anti-inflammation, and may be used as supplements for amelioration or prevention of COVID-19 symptoms, as well as the representative compounds can be used for quality control of PAFYY in the future.

Teachers' Experiences with and Perceptions of Virtual Manipulatives Following the COVID-19 Pandemic.

While the use of virtual manipulatives (VM) is rising in classrooms, there is still limited research. regarding teacher experiences with and perceptions of virtual manipulatives. Most of the research regarding teacher perceptions of VM has focused only on short-term uses following professional development sessions and none has highlighted the experiences of teachers using them during emergency remote teaching during COVID-19. The purpose of this study was to explore teacher perceptions and. experiences with virtual manipulatives following emergency remote teaching during COVID-19. To achieve this, the researchers conducted an online survey to gather data on educator's (n = 103) experiences, perceptions, and usage of virtual manipulatives. The qualitative and quantitative data show that educators feel that VM are a valid and feasible support of mathematics instruction when physical manipulatives are not available. Results regarding usage of virtual manipulatives including frequency of use, standards taught, and types used are presented and discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s11528-022-00796-9.

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The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

Drug-Target Network Study Reveals the Core Target-Protein Interactions of Various COVID-19 Treatments.

The coronavirus disease 2019 (COVID-19) pandemic has caused a dramatic loss of human life and devastated the worldwide economy. Numerous efforts have been made to mitigate COVID-19 symptoms and reduce the death rate. We conducted literature mining of more than 250 thousand published works and curated the 174 most widely used COVID-19 medications. Overlaid with the human protein-protein interaction (PPI) network, we used Steiner tree analysis to extract a core subnetwork that grew from the pharmacological targets of ten credible drugs ascertained by the CTD database. The resultant core subnetwork consisted of 34 interconnected genes, which were associated with 36 drugs. Immune cell membrane receptors, the downstream cellular signaling cascade, and severe COVID-19 symptom risk were significantly enriched for the core subnetwork genes. The lung mast cell was most enriched for the target genes among 1355 human tissue-cell types. Human bronchoalveolar lavage fluid COVID-19 single-cell RNA-Seq data highlighted the fact that T cells and macrophages have the most overlapping genes from the core subnetwork. Overall, we constructed an actionable human target-protein module that mainly involved anti-inflammatory/antiviral entry functions and highly overlapped with COVID-19-severity-related genes. Our findings could serve as a knowledge base for guiding drug discovery or drug repurposing to confront the fast-evolving SARS-CoV-2 virus and other severe infectious diseases.

Case report of acute encephalitis following the AstraZeneca COVID-19 vaccine.

Coronavirus disease 2019 (COVID-19) vaccines have proven to be safe, effective and life-saving. However, little information is available on the neurological complications of COVID-19 vaccine. Here, we report a case who developed acute encephalomyelitis 1 week after being vaccinated with AstraZeneca COVID-19 vaccine (AZ vaccine). Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was also suspected. After intravenous dexamethasone and subcutaneous fondaparinux therapy, he returned to normal life without neurological sequelae. Four months later, he received Moderna COVID-19 vaccine without any sequelae.

The feasibility, safety, and efficacy of Paxlovid treatment in SARS-CoV-2-infected children aged 6-14 years: a cohort study.

Background: Paxlovid is recognized as an effective medication in preventing the progression of coronavirus disease of 2019 (COVID-19) to severe form in adults; however, its efficacy has remained unknown in pediatric cases. This study aimed to analyze the feasibility, safety, and efficacy of Paxlovid treatment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children aged 6-14 years. Methods: We conducted a cohort study based on prospectively collected clinical data. We recruited 5 pediatric cases with underlying diseases treated with Paxlovid from 7 April 2022 to 26 May 2022 and 30 age-matched patients with underlying diseases who were not treated with Paxlovid as controls. The safety and efficacy of Paxlovid were primarily assessed by inter-group comparisons. Results: Of the 5 Paxlovid-treated cases, including 1 male and 4 females, 3 and 2 cases were mildly and moderately ill, respectively. The underlying diseases included congenital heart defects, cerebral palsy, Down syndrome, and leukemia. Only 1 patient had received 1 dose of an inactivated SARS-CoV-2 vaccine. Paxlovid was initiated within 5 days after the onset of symptoms in all cases. Comedications were used in 2 cases. In the safety analyses, after Paxlovid initiation, 1 patient had transient diarrhea, and 1 patient had transiently elevated liver enzymes [alanine transaminase (ALT), 125 U/L; aspartate transaminase (AST), 83 U/L; normal range, <40 U/L]. In the efficacy analyses, all 5 Paxlovid-treated cases recovered, with the respective viral shedding times of 11, 4, 10, 9, and 9 days. Compared with age-matched controls, the viral shedding times were not significantly different between groups. Conclusions: Based on the current small sample size study, Paxlovid is a feasible option for treating SARS-CoV-2-infected children aged 6-14 years with underlying diseases. However, the safety and efficacy of Paxlovid warrant further large-scale studies.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

A phase II study of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer.

BACKGROUND: The aim of this prospective, pilot, single-arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). METHODS: This phase II study was conducted at Fudan University Shanghai Cancer Center between December 2018 and December 2020. All patients received standard chemotherapy (etoposide plus cisplatin/carboplatin) consisting of four courses and anlotinib at 12 mg once per day for 2 weeks followed by a one-week rest. Anlotinib administration was continued until disease progression, intolerable adverse events (AEs) or patient withdrawal from the study. The primary outcome measure was progression-free survival (PFS). The secondary outcome measures were overall survival (OS), objective control rate (ORR), disease control rate (DCR) and AEs. RESULTS: Thirty-seven patients were included in this study, and 30 patients were eligible for efficacy analysis. ORR and DCR were 90.0% and 96.7%, respectively. The estimated PFS and OS were 6.0 months (95% CI: 1.1-11.9 months) and 14.0 months (95% CI: 8.6-19.4 months), respectively. No unexpected adverse effects were reported. Hypertension (20/37, 54.1%), anemia (16/37, 43.2%), alopecia (15/37, 40.5%), elevated transaminases (9/37, 24.3%) and alkaline phosphatase (9/37, 24.3%) were the most commonly reported AEs. Thirteen patients (35.1%) reported grade 3-5 AEs. No treatment-related deaths occurred during this study. CONCLUSION: The addition of anlotinib to standard etoposide/platinum chemotherapy achieved encouraging PFS and OS in previously untreated ES-SCLC patients, with an acceptable tolerability profile and no new safety signals observed.