Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system.

Background: Risankizumab, a humanized IgG1 monoclonal antibody that selectively inhibits IL-23, is currently approved for the treatment of moderate-to-severe plaque psoriasis and Crohn's disease. The real-world safety study of risankizumab in a large- sample population is currently lacking. The aim of this study was to evaluate risankizumab-associated adverse events (AEs) and characterize the clinical priority through the data mining of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses were performed by calculating the reporting odds ratios (RORs), deemed significant when the lower limit of the 95% confidence interval was greater than 1, to quantify the signals of risankizumab-related AEs from the second quarter (Q2) of 2019 to 2022 Q3. Serious and non-serious cases were compared, and signals were prioritized using a rating scale. Results: Risankizumab was recorded in 10,235 reports, with 161 AEs associated with significant disproportionality. Of note, 37 PTs in at least 30 cases were classified as unexpected AEs, which were uncovered in the drug label, such as myocardial infarction, cataract, pancreatitis, diabetes mellitus, stress, and nephrolithiasis. 74.68%, 25.32%, and 0% PTs were graded as weak, moderate, and strong clinical priorities, respectively. A total of 48 risankizumab-related AEs such as pneumonia, cerebrovascular accident, cataract, loss of consciousness, cardiac disorder, hepatic cirrhosis, and thrombosis, were more likely to be reported as serious AEs. The median TTO of moderate and weak signals related to risankizumab was 115 (IQR 16.75-305) and 124 (IQR 29-301) days, respectively. All of the disproportionality signals had early failure type features, indicating that risankizumab-associated AEs gradually decreased over time. Conclusion: Our study found potential new AE signals and provided valuable evidence for clinicians to mitigate the risk of risankizumab-associated AEs based on an extensive analysis of a large-scale postmarketing international safety database.

Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

Impact of consumer global–local identity on attitude towards and intention to buy local foods

The outbreak of the coronavirus pandemic (Covid-19) has profoundly affected the food systems, leading to consumer concerns about the lack of reliability and safety of global foods and a growing trend towards consuming local foods. Consumers have formed multicultural identities, such as global identity and local identity, under the influences of global and local consumer culture. This study develops a conceptual model to examine the impact of consumer global–local identity, locavorism, and consumer xenocentrism on consumer attitudes towards and intentions to buy local foods during Covid-19 crisis. We conducted an online survey in China that measured the constructs using established scales. Using structural equation modelling to test the proposed hypotheses, we find that: a higher degree of global identity will lead to a higher degree of consumer xenocentrism, whereas a higher degree of local identity will lead to a lower degree of consumer xenocentrism;local identity significantly and positively predicts locavorism;contrary to the prediction, the impact of global identity on locavorism is not significant;a higher degree of consumer xenocentrism will lead to a lower degree of attitude towards buying local foods. Theoretically, our findings contribute to the understanding of literature on local food consumption, consumer global–local identity, and consumer xenocentrism. Local food marketers can obtain practical insights based on our findings.

COVID-19 impact on the operational efficiency of a downtown hotel

This research article utilizes a bootstrap DEA approach for assessing the operational efficiency of a single southwestern downtown hotel during the COVID-19 pandemic. The hotel's performance is benchmarked throughout a 12-month period, which includes a two-month shutdown period due to COVID-19. The bias-corrected technical and scale efficiencies before and after the pandemic shutdown are estimated. The undesirable effect of the COVID-19 pandemic is significantly unquestionable. Results suggest that the hotel was not operating on the optimum scale before the shutdown;furthermore, the pandemic aggravated its performance even more. Interestingly, the hotel's technical efficiency was not affected by the pandemic, confirming the scale of operations as the highly significant improvement opportunity after the shutdown. Managerial recommendations are discussed as well. [ FROM AUTHOR] Copyright of Anatolia: An International Journal of Tourism & Hospitality Research is the property of Routledge 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.)

Sources, analysis, and health implications of atmospheric microplastics

Microplastics (MPs) are emerging environmental contaminants pervasive in the environment. Studies have revealed that the majority of airborne MPs are in the form of fiber. Inhaled atmospheric MPs adversely impact human health, causing inflammation and oxidative stress. Atmospheric MPs may also carry hazardous chemical pollutants in addition to heavy metals. Many research studies have been conducted about MPs' presence in the environmental components, however questions about the presence and identification of atmospheric MPs remained unanswered. Based on the mentioned research gaps, this study examined the sources and abundance of MPs in the atmosphere and their generation, accumulation, and fate. The paper further studies and evaluates current methods for identifying and assessing airborne MPs and their impact on human health and the environment. According to the study findings, there are flaws and complexity in MPs assessment and technical procedures, which further challenges data comparability and dependability. In order to ensure data comparability and reliability, the abundance of atmospheric MPs needs to be expressed using a unified and standard methodology. Innovative and well-established identification methods, strategies to minimize the impacts of MPs, and appropriate steps to reduce this global pollution are required for the current state of MPs. It also provides an overview of atmospheric MPs' characteristics, sources, and airborne transmission and deposition mechanisms. Advances in bacterial degradation, sunlight-driven photocatalysts, fuels, and biodegradable plastics could revolutionize future studies on reducing plastic pollution. Future studies should include more research on the various aspects of atmospheric MPs. Despite several research studies conducted on the presence and identification of MPs in various environmental components, many questions regarding MPs in the atmosphere and from the perspectives of COVID-19 and One Health still need to be answered. This study will help the key stakeholders and policymakers in safeguarding public health and environment from the threats posed by airborne MPs.

A Vaccine of SARS-CoV-2 S Protein RBD Induces Protective Immunity.

The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to the world in many aspects. There is an urgent requirement for an effective preventive vaccine. The receptor binding domain (RBD), located on the spike (S) gene, is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor of host cells. The RBD protein is an effective and safe antigen candidate. The six-helix bundle (6HB) "molecular clamp" is a novel thermally-stable trimerization domain derived from a human immunodeficiency virus (HIV) gp41 protein segment. We selected the baculovirus system to fuse and express the RBD protein and 6HB for imitating the natural trimeric structure of RBD, named RBD-6HB. Recombinant RBD-6HB was successfully obtained from the cell culture supernatant and purified to high homogeneity. The purity of the final protein preparation was more than 97%. The results showed that the protein was identified as a homogeneous polymer. Further studies showed that the RBD-6HB protein combined with AL/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges. Our findings highlight the importance of trimerized SARS-CoV-2 S protein RBD in designing SARS-CoV-2 vaccines and provide a rationale for developing a protective vaccine through the induction of antibodies against the RBD domain.

Effects of a online brief modified mindfulness-based stress reduction therapy for anxiety among Chinese adults: A randomized clinical trial

The COVID-19 pandemic has exacerbated anxiety and related symptoms among the general population. In order to cope with the mental health burden, we developed an online brief modified mindfulness-based stress reduction (mMBSR) therapy. We performed a parallel-group randomized controlled trial to evaluate the efficacy of the mMBSR for adult anxiety with cognitive-behavioral therapy (CBT) as an active control. Participants were randomized to mMBSR, CBT or waitlist group. Those in the intervention arms performed each therapy for 6 sections in 3 weeks. Measurements were conducted at baseline, post-treatment and 6 months post-treatment by Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Patient Health Questionnaire-15, reverse scored Cohen Perceived Stress scale, Insomnia Severity Index, and Snaith-Hamilton Pleasure Scale. 150 participants with anxiety symptoms were randomized to mMBSR, CBT or waitlist group. Post intervention assessments showed that mMBSR improved the scores of all the six mental problem dimensions (anxiety, depression, somatization, stress, insomnia, and the experience of pleasure) significantly compared to the waitlist group. During 6-month post treatment assessment, the scores of all six mental problem dimensions in the mMBSR group still showed improvement compared to baseline and showed no significant difference with the CBT group. Our results provide positive evidence for the efficacy and feasibility of an online brief modified MBSR program to alleviate anxiety and related symptoms of individuals from the general population, and the therapeutic benefits of mMBSR persisted for up to six months. This low resource-consuming intervention could facilitate the challenges of supplying psychological health therapy to large scale of population.

Pre-enriched saline gargle samples for detection of SARS-CoV-2.

A self­collected gargle sample, which avoids discomfort and largely reduces the dependency on medical resources, is emerging for detection of SARS­CoV­2. However, the incomplete usage of starting materials for both routine oropharyngeal swabs (OPS)/nasopharyngeal swabs (NPS) and saline gargle (SG) samples implies sensitivity can be further improved. Presented here is a bead­based strategy for pre­enrichment of SG samples, and results revealed that it acquired about 20 times the starting materials obtained from OPS samples for downstream detection of SARS­CoV­2. The sensitivity and specificity of this pre­enrichment strategy were validated in 100 paired pre­enriched saline gargle (PenSG) and OPS samples and 89 PenSG samples from healthy volunteers. In addition to detection of SARS­CoV­2, this pre­enrichment strategy may also be implemented in more clinical settings to optimize detection of other diseases.

Effects of a online brief modified mindfulness-based stress reduction therapy for anxiety among Chinese adults: A randomized clinical trial.

The COVID-19 pandemic has exacerbated anxiety and related symptoms among the general population. In order to cope with the mental health burden, we developed an online brief modified mindfulness-based stress reduction (mMBSR) therapy. We performed a parallel-group randomized controlled trial to evaluate the efficacy of the mMBSR for adult anxiety with cognitive-behavioral therapy (CBT) as an active control. Participants were randomized to mMBSR, CBT or waitlist group. Those in the intervention arms performed each therapy for 6 sections in 3 weeks. Measurements were conducted at baseline, post-treatment and 6 months post-treatment by Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Patient Health Questionnaire-15, reverse scored Cohen Perceived Stress scale, Insomnia Severity Index, and Snaith-Hamilton Pleasure Scale. 150 participants with anxiety symptoms were randomized to mMBSR, CBT or waitlist group. Post intervention assessments showed that mMBSR improved the scores of all the six mental problem dimensions (anxiety, depression, somatization, stress, insomnia, and the experience of pleasure) significantly compared to the waitlist group. During 6-month post treatment assessment, the scores of all six mental problem dimensions in the mMBSR group still showed improvement compared to baseline and showed no significant difference with the CBT group. Our results provide positive evidence for the efficacy and feasibility of an online brief modified MBSR program to alleviate anxiety and related symptoms of individuals from the general population, and the therapeutic benefits of mMBSR persisted for up to six months. This low resource-consuming intervention could facilitate the challenges of supplying psychological health therapy to large scale of population.

A micro-sized vaccine based on recombinant Lactiplantibacillus plantarum fights against SARS-CoV-2 infection via intranasal immunization.

COVID-19 has globally spread to burden the medical system. Even with a massive vaccination, a mucosal vaccine offering more comprehensive and convenient protection is imminent. Here, a micro-sized vaccine based on recombinant Lactiplantibacillus plantarum (rLP) displaying spike or receptor-binding domain (RBD) was characterized as microparticles, and its safety and protective effects against SARS-CoV-2 were evaluated. We found a 66.7% mortality reduction and 100% protection with rLP against SARS-CoV-2 in a mouse model. The histological analysis showed decreased hemorrhage symptoms and increased leukocyte infiltration in the lung. Especially, rLP:RBD significantly decreased pulmonary viral loads. For the first time, our study provides a Lactiplantibacillus plantarum-vectored vaccine to prevent COVID-19 progress and transmission via intranasal vaccination.

Important revelations of different degrees of COVID-19 lockdown on improving regional air quality: a case study of Shijiazhuang, China.

To control the spread of COVID-19, Shijiazhuang implemented two lockdowns of different magnitudes in 2020 (lockdown I) and 2021 (lockdown II). We analyzed the changes in air quality index (AQI), PM2.5, O3, and VOCs during the two lockdowns and the same period in 2019 and quantified the effects of anthropogenic sources during the lockdowns. The results show that AQI decreased by 13.2% and 32.4%, and PM2.5 concentrations decreased by 12.9% and 42.4% during lockdown I and lockdown II, respectively, due to the decrease in urban traffic mobility and industrial activity levels. However, the sudden and unreasonable emission reductions led to an increase in O3 concentrations by 160.6% and 108.4%, respectively, during the lockdown period. To explore the causes of the O3 surge, the major precursors NOx and VOCs were studied separately, and the main VOCs species affecting ozone formation during the lockdown period and the source variation of VOCs were identified, and it is important to note that the relationship between diurnal variation characteristics of VOCs and cooking became apparent during the lockdown period. These findings suggest that regional air quality can be improved by limiting production, but attention should be paid to the surge of O3 caused by unreasonable emission reductions, clarifying the control priorities for urban O3 management.

Evaluation of ferritin level in COVID-19 patients and its inflammatory response.

The importance of ferritin as an inflammatory marker is well recognized. However, it is unknown whether this differs between Covid-19 and non-Covid-19 patients. The blood levels of ferritin, white blood cells (WBC), C-reactive protein (CRP), and lactate dehydrogenase may all be measured to check whether there is a difference. The researchers want to see if the inflammatory process changes between these two kinds (LDH). Methodology: Blood samples were collected from 119 COVID-19 patients in the hospital and 50 healthy persons. Corona virus was discovered when a nasopharyngeal swab was collected and tested using the RT-PCR technique. Ferritin, LDH, WBC, and CRP were also tested using Min Vidus, AccEnT 200, Ruby system, and Latx in that sequence. The study revealed that COVID-19 patients had higher levels of ferritin, WBC, CRP, and LDH in their blood than healthy people, with values of 539,08 ng/mL, 44.7109/L, 22.95 mg/L, and 403.95 U/L for COVID-19 patients versus 77.103 ng/mL, 4.9.4109/L, 6.53 mg/L, and 171.56 U/L for healthy people. According to the existing data, males are more likely to be infected with COVID-19 (81%) than females (32%), and females had greater ferritin, CRP, WBC, and LDH levels than males. Because they are related to an optimum test for predicting COVID-19 infection, the recommended cut-off values for ferritin, WBC, CRP, and LDH are 109.8 ng/mL, 14.9109/L, 10.15 mg/L, and 229.33 U/L, respectively. Finally, an increase in ferritin levels in the inflammatory response to COVID-19 is linked to an increase in inflammatory markers including CRP, WBC, and LDH, which may assist in the diagnosis of COVID-19 infection.

Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice.

Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

Current understanding on long non-coding RNAs in immune response to COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic threatening the lives and health of people worldwide. Currently, there are no effective therapies or available vaccines for COVID-19. The molecular mechanism causing acute immunopathological diseases in severe COVID-19 is being investigated. Long noncoding RNAs (lncRNAs) have been proven to be involved in many viral infections, such as hepatitis, influenza and acquired immune deficiency syndrome. Many lncRNAs present differential expression between normal tissue and virus-infected tissue. However, the role of lncRNAs in SARS-CoV-2 infection has not been fully elucidated. This study aimed to review the relationship between lncRNAs and viral infection, interferon and cytokine storms in COVID-19, hoping to provide novel insights into promising targets for COVID-19 treatment.

The S protein of a novel recombinant PEDV strain promotes the infectivity and pathogenicity of PEDV in mid-west China.

Porcine epidemic diarrhoea virus (PEDV) is an emerging and re-emerging swine enterovirus that causes highly contagious diarrhoea and mortality in piglets. To better understand the current prevalence of PEDV in mid-west China, and to find out the reason for the re-emergence of PEDV from the viral genomic characteristics. Herein, we firstly investigated epidemiology of PEDV in mid-west China from 2019 to 2020. A total of 62.23% (257/413) of diarrhoea samples were positive for PEDV, and the PEDV-positive cases were mainly detected in winter. Then, we selected the SXSL strain as a representative strain to study the genetic and pathogenic characterization of PEDV pandemic strains in mid-west China. The recombination analysis showed that SXSL strain was a recombinant strain, and the major and minor parent strains of the recombination are CH/SCZJ/2018 strain and GDS48 strain, respectively. Complete genome sequencing and homology analysis showed that the S protein of SXSL strain contained multiple amino acid indels and mutations compared to the PEDV representative strains. Furthermore, we evaluated the effect of S protein on the infectivity and pathogenicity of PEDV by the PEDV reverse genetics system, and results showed that SXSL S protein increased the infectivity and pathogenicity of chimeric virus. Overall, our findings provided important information for understanding the roles of S protein in the prevalence of PEDV in mid-west China and developing vaccines based on PEDV pandemic strains.

A Bibliometric Analysis of Psychological Research on COVID-19

The coronavirus disease 2019(COVID-19) pandemic has had a profound impact on people's mental health, and psychological research on COVID-19 has been growing exponentially. Therefore, this study aims to understand the development trends, research collaboration, and knowledge exchange of psychological research on COVID-19, and focuses on scientific collaboration, hotspots, and the knowledge base. A total of 8,235 documents were collected from the Web of Science database. VOSviewer was used to conduct the descriptive and bibliometric analysis. The results show that the U.S.A. is the most productive country, with the most citations, the most links with other countries, and the strongest total link strength with other countries. Stanford University in the U.S.A. has the strongest total link strength with other research institutions. Mark Griffiths has the most co-author publications with other authors, and Handan Akkas has collaborated with the most authors. According to the analysis of keywords, research hotspots are categorized into five clusters as follows: "COVID-19 pandemic and public health", "anxiety and depression", "emotional regulation and coping", "sample characteristics and interventions", and "scale development and investigation". The knowledge base of COVID-19 psychological research covers four major domains as follows: "COVID-19 psychological research", "mental scales", "SARS related research", and "statistical applications. Accordingly, this study proposes enlightenment in psychological research on COVID-19 that international cooperation can develop short-term and long-term strategies for mental health, and make good use of mental scales to understand and respond to maintain mental health. Ultimately, sharing the research results will bring more opportunities to solve problems for COVID-19 psychological research.