Computational decision-support tools for urban design to improve resilience against COVID-19 and other infectious diseases: A systematic review.

The COVID-19 pandemic highlighted the need for decision-support tools to help cities become more resilient to infectious diseases. Through urban design and planning, non-pharmaceutical interventions can be enabled, nudging behaviour change and facilitating lower risk buildings and public spaces. Computational tools, including computer simulation, statistical models, and artificial intelligence, were used to support responses in the current pandemic as well as to the previous infectious diseases. Our multidisciplinary research group systematically reviewed state-of-the-art literature to propose a toolkit that employs computational modelling for various interventions and urban design processes. From 8,737 records returned from databases, 109 records were selected and analysed based on the pathogen type, transmission mode and phase, design intervention and process, as well as modelling methodology (method, goal, motivation, focus, and indication to urban design). We also explored the relationship between infectious disease and urban design as well as computational modelling supports, including specific models and parameters. The proposed toolkit will help designers, planners, and computer modellers to select relevant approaches to evaluate and consider design decisions depending on the disease, geographic context, design stages, and spatial and temporal scales. The findings herein can be regarded as stand-alone tools, particularly for COVID-19 or be incorporated into broader frameworks to help cities become more resilient to future disasters.

Work: A Social Determinant of Health Worth Capturing.

Work is a recognized social determinant of health. This became most apparent during the COVID-19 pandemic. Workers, particularly those in certain industries and occupations, were at risk due to interaction with the public and close proximity to co-workers. The purpose of this study was to assess how states collected work and employment data on COVID-19 cases, characterizing the need for systematic collection of case-based specific work and employment data, including industry and occupation, of COVID-19 cases. A survey was distributed among state occupational health contacts and epidemiologists in all 50 states to assess current practices in state public health surveillance systems. Twenty-seven states collected some kind of work and employment information from COVID-19 cases. Most states (93%) collected industry and/or occupation information. More than half used text-only fields, a predefined reference or dropdown list, or both. Use of work and employment data included identifying high risk populations, prioritizing vaccination efforts, and assisting with reopening plans. Reported barriers to collecting industry and occupation data were lack of staffing, technology issues, and funding. Scientific understanding of work-related COVID-19 risk requires the systematic, case-based collection of specific work and employment data, including industry and occupation. While this alone does not necessarily indicate a clear workplace exposure, collection of these data elements can help to determine and further prevent workplace outbreaks, thereby ensuring the viability of the nation's critical infrastructure.

The third inactivated vaccine booster dramatically enhanced SARS-CoV-2 antibody responses and did not influence the profile of prothrombotic antibody.

OBJECTIVE: The purpose of this study is to investigate the production of both SARS-CoV-2-specific antibodies and autoantibodies in serum following the third booster vaccination of the inactivated COVID-19 vaccine, and to study the effect of B cell subsets with CD27 and CD38 phenotypes in peripheral blood on antibody production. METHODS: Routine blood indexes, SARS-CoV-2 antibodies, platelet factor 4 and seven antiphospholipid antibodies were detected both before and 2 months after vaccination in the medical staff of the Zhongnan Hospital of Wuhan University. Peripheral blood B cell subtypes were detected prior to vaccination. RESULTS: Following immunization, the positive rate of anti-N-S1 IgG had increased from 24.8% to 91.3% and the average antibody concentration had increased by 11 times. The positive rate of NAb had increased from 24.8% to 91.3%, the average antibody concentration had increased by 12 times, and the primary increased anti-S1 IgG subtype was that of IgG1. Peripheral blood CD27+CD38+ B cells were positively correlated with antibody levels after vaccination and were a predictor of the antibody response. In addition, although some indicators showed slight absolute changes, the blood parameters and antiphospholipid antibodies of most volunteers were normal both before and after COVID-19 inactivated vaccine inoculation, and there was no statistical difference in abnormal rates either before or after inoculation. CONCLUSION: Antibodies in vivo were increased after vaccination with the inactivated vaccine, and IgG1 was the main subtype involved in response to the vaccine. Vaccination with the inactivated COVID-19 vaccine did not appear to affect thrombus-related autoantibodies. This article is protected by copyright. All rights reserved.

Redistribution and activation of CD16brightCD56dim NK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination (preprint)

With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 Omicron BA.2-infected patients enrolled, 102 were unvaccinated controls and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, overall clinical symptoms, and a moderate rise in body temperature. Omicron BA.2-infected individuals were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T and B lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16brightCD56dim subsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-{gamma} secretion and stronger cytotoxic potential in Omicron BA.2-infected patients after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16brightCD56dim NK cell subsets against viral infections, and could facilitate the clinical management of Omicron BA.2-infected patients.

Recursive Zero-COVID model and quantitation of control efforts of the Omicron epidemic in Jilin province.

Since the beginning of March 2022, the epidemic due to the Omicron variant has developed rapidly in Jilin Province. To figure out the key controlling factors and validate the model to show the success of the Zero-COVID policy in the province, we constructed a Recursive Zero-COVID Model quantifying the strength of the control measures, and defined the control reproduction number as an index for describing the intensity of interventions. Parameter estimation and sensitivity analysis were employed to estimate and validate the impact of changes in the strength of different measures on the intensity of public health preventions qualitatively and quantitatively. The recursive Zero-COVID model predicted that the dates of elimination of cases at the community level of Changchun and Jilin Cities to be on April 8 and April 17, respectively, which are consistent with the real situation. Our results showed that the strict implementation of control measures and adherence of the public are crucial for controlling the epidemic. It is also essential to strengthen the control intensity even at the final stage to avoid the rebound of the epidemic. In addition, the control reproduction number we defined in the paper is a novel index to measure the intensity of the prevention and control measures of public health.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis.

Objectives: The main objectives of this study were to investigate the efficacy of the nucleotide analog GS-441524 in combination with the 3C-like protease inhibitor GC376 for the treatment of naturally aquired feline infectious peritonitis (FIP) and to test whether their combination shortens the dosing period and improves the cure rate. Methods: In total, 46 FIP-affected cats were enrolled in this experiment, including 36 with wet FIP (29 with abdominal effusion, six with thoracic effusion, and one with thoracic+abdominal effusion), and 10 with dry FIP. The cats were aged from 3 to 96 months. Thoracic+abdominal effusion, lymph-node puncture fluid and perirenal puncture fluid was collected from the affected cats for qPCR testing, and all 46 cats were positive for feline coronavirus (FCoV). The cats divided into different dose groups, all treated for 4 weeks: group 1 (GS-441524, 5 mg/kg.sc.q.24 h; GC376, 20 mg/kg.sc.q.12 h), group 2 (GS-441524, 2.5 mg/kg.sc.q.24 h; GC376, 20 mg/kg.sc.q.12 h), group 3 (GS-441524, 2.5 mg/kg.sc.q.24 h; GC376, 10 mg/kg.sc.q.12 h), and group 4 (GS-441524, 5 mg/kg.sc.q.24 h; GC376, 10 mg/kg.sc.q.12 h). Results: After the 4-week combination treatment, 45 of the 46 (97.8%) cats survived, and 43 of those became clinically normal. Two cats required longer (7 to 12 weeks) treatment to achieve full recovery. As of writing (10 months after completion of the trial), all 45 cats were alive and no relapse was observed. Conclusions and relevance: GS-441524 combined with GC376 can be safely and effectively used to treat FIP and reduces the treatment period to 4 weeks, with an excellent cure rate.

Human Mobility Modeling During the COVID-19 Pandemic via Deep Graph Diffusion Infomax (preprint)

Non-Pharmaceutical Interventions (NPIs), such as social gathering restrictions, have shown effectiveness to slow the transmission of COVID-19 by reducing the contact of people. To support policy-makers, multiple studies have first modeled human mobility via macro indicators (e.g., average daily travel distance) and then studied the effectiveness of NPIs. In this work, we focus on mobility modeling and, from a micro perspective, aim to predict locations that will be visited by COVID-19 cases. Since NPIs generally cause economic and societal loss, such a micro perspective prediction benefits governments when they design and evaluate them. However, in real-world situations, strict privacy data protection regulations result in severe data sparsity problems (i.e., limited case and location information). To address these challenges, we formulate the micro perspective mobility modeling into computing the relevance score between a diffusion and a location, conditional on a geometric graph. we propose a model named Deep Graph Diffusion Infomax (DGDI), which jointly models variables including a geometric graph, a set of diffusions and a set of locations.To facilitate the research of COVID-19 prediction, we present two benchmarks that contain geometric graphs and location histories of COVID-19 cases. Extensive experiments on the two benchmarks show that DGDI significantly outperforms other competing methods.

Case Report: A case of advanced duodenal adenocarcinoma in complete remission after chemotherapy combined with targeted therapy and radiotherapy.

Duodenal adenocarcinoma (DA) is an extremely rare and highly aggressive malignant tumor of the digestive system. Due to the lack of specific clinical characteristics, it is easy to misdiagnosis and miss diagnosis, and the lack of specific consensus and recommendation for treatment, so it often refers to stomach cancer and colorectal cancer. Now, we report a case of a patient with advanced DA who achieved complete remission (CR) after undergoing chemoradiotherapy combined with targeted therapy. The patient was pathologically diagnosed with DA after radical surgery in October 2020, and he failed to undergo adjuvant chemotherapy on time due to the COVID-19 outbreak. The patient found multiple lymph node liver and abdominal metastases 6 months after the operation. Considering the progression of the disease, XELOX regimen (oxaliplatin + capecitabine) chemotherapy was given for 1 cycle. After 1 cycle of treatment, the tumor markers remained elevated; the carcinoembryonic antigen (CEA) was 5.03 ng/ml (0-5 ng/ml), and the carbohydrate antigen 19-9 (CA19-9) was 747.30 U/ml (0-37 U/ml). The patient also developed intolerable capecitabine-related treatment-related adverse events (TRAEs), namely, hand-foot syndrome. For the above reasons, capecitabine was replaced as S-1 at cycle 2, and the chemotherapy regimen became SOX (oxaliplatin + S-1); bevacizumab injection was also added to the SOX regimen, and it was further treated regularly for 7 cycles with the regimen of SOX plus bevacizumab. Liver metastases showed a continuous narrowing trend throughout the treatment period; tumor markers also showed a downward trend. Finally, the patient achieved complete remission (CR) at cycle 7. After completion of chemotherapy, radiotherapy was administered to the resistant metastatic lymph nodes present in the patient's abdominal cavity for a total of 10 times. However, the patient developed severe bone marrow suppression and obstructive jaundice during the course of radiotherapy and finally failed to complete the radiotherapy plan. Currently, the patient continued maintenance therapy with bevacizumab and S-1 and showed no recurrence or metastasis after review. In this case of advanced DA, we referred to both CRC and gastric cancer in the treatment regimen of the patient. At the same time, targeted drugs and radiotherapy were also added to the basis of chemotherapy, which has no clear consensus recommendation or case for reference in the treatment of advanced DA. Thankfully, the patient's disease was controlled and remained stable after treatment with this regimen. Therefore, for patients with advanced DA who lack standardized treatment regimens and guidelines, the combination of chemotherapy with targeted therapy and radiotherapy may be one of the effective treatment modalities.

Group Differences: The Relationship between Social Media Use and Depression during the Outbreak of COVID-19 in China.

The outbreak of COVID-19 at the end of 2019 triggered more psychological problems than usual among the public. During this epidemic, the use of social media was very high, and several studies confirmed a positive correlation between social media use and people's psychological problems. The Chinese government has subsequently implemented a series of policies concerning the social media environment to tackle this "infodemic". After the containment of the first COVID-19 outbreak, China saw a new wave of COVID-19 cases in Shijiazhuang, Hebei Province in January 2021. How the optimized social media could have impacted public mental health remained to be revealed. Our research data come from an online survey of Chinese residents during the regional epidemic in Shijiazhuang, with a total of 904 valid samples from 18 different provinces in China. The results showed that this new round of outbreaks caused a high incidence of depression (38.9%) among the public. Compared with relatively advantaged groups, disadvantaged groups have a higher depression. Attributed to the optimization of the social media environment, the prevalence of social media use during the epidemic helped to markedly mitigate anxieties from depression. This is particularly demonstrated in vulnerable groups. We found, for the first time, a change in the relationship between social media use and resident depression, and more importantly, a stronger correlation between social media use and depression in relatively disadvantaged groups. Therefore, during the epidemic, actively optimizing the social media environment has a significant and positive effect on the mental health of residents, especially vulnerable groups.

Application of radical mastectomy in ambulatory surgery centres under COVID-19 (preprint)

Background Breast cancer has surpassed lung cancer as the most common cancer. Day surgery for breast cancer has been widely carried out worldwide, but the development of day surgery in China is relatively slow. To reduce the spread of coronavirus 2019 (COVID-19), major surgery centres have optimized the management procedures of day surgery to different degrees. However, relevant research on whether the rapid turnover of day surgery and the excessive human resources placed in the prevention and control of the COVID-19 epidemic will affect the quality of day surgery is lacking.Method The demographic data, clinical data and postoperative complications of breast cancer patients in the single medical group of West China Hospital of Sichuan University from March 2020 to June 2021 were retrospectively collected, and the complications after discharge and the safety of day surgery were analysed.Results The average age significantly differed between the ward surgery group (WS) and the day surgery group (DS) (P = 0.030). Regarding postoperative complications, no significant differences were detected in total surgical complications (P = 0.676) or anaesthesia complications (P = 0.126) between the two groups. In the logistic analysis, day surgery was not a risk factor for postoperative complications during the COVID-19 pandemic (P = 0.676, OR = 1.154, 95% CI: 0.590–2.257). An increase in age significantly increased the incidence of postoperative surgical complications (P = 0.024, OR = 1.051, 95% CI: 1.007–1.097). At the same time, lymph node dissection after sentinel lymph node biopsy also led to an increase in the incidence of postoperative surgical complications (P = 0.030, OR = 3.372, 95% CI: 1.125–10.106). In the survival curve, no significant difference in DFS was detected between the two groups (P = 0.353).Conclusion Radical mastectomy at day surgery centres is safe and reliable under strict COVID-19 management guidelines.

Assessing the mechanism of citywide test-trace-isolate Zero-COVID policy and exit strategy of COVID-19 pandemic.

BACKGROUND: Countries that aimed for eliminating the cases of COVID-19 with test-trace-isolate policy are found to have lower infections, deaths, and better economic performance, compared with those that opted for other mitigation strategies. However, the continuous evolution of new strains has raised the question of whether COVID-19 eradication is still possible given the limited public health response capacity and fatigue of the epidemic. We aim to investigate the mechanism of the Zero-COVID policy on outbreak containment, and to explore the possibility of eradication of Omicron transmission using the citywide test-trace-isolate (CTTI) strategy. METHODS: We develop a compartmental model incorporating the CTTI Zero-COVID policy to understand how it contributes to the SARS-CoV-2 elimination. We employ our model to mimic the Delta outbreak in Fujian Province, China, from September 10 to October 9, 2021, and the Omicron outbreak in Jilin Province, China for the period from March 1 to April 1, 2022. Projections and sensitivity analyses were conducted using dynamical system and Latin Hypercube Sampling/ Partial Rank Correlation Coefficient (PRCC). RESULTS: Calibration results of the model estimate the Fujian Delta outbreak can end in 30 (95% confidence interval CI: 28-33) days, after 10 (95% CI: 9-11) rounds of citywide testing. The emerging Jilin Omicron outbreak may achieve zero COVID cases in 50 (95% CI: 41-57) days if supported with sufficient public health resources and population compliance, which shows the effectiveness of the CTTI Zero-COVID policy. CONCLUSIONS: The CTTI policy shows the capacity for the eradication of the Delta outbreaks and also the Omicron outbreaks. Nonetheless, the implementation of radical CTTI is challenging, which requires routine monitoring for early detection, adequate testing capacity, efficient contact tracing, and high isolation compliance, which constrain its benefits in regions with limited resources. Moreover, these challenges become even more acute in the face of more contagious variants with a high proportion of asymptomatic cases. Hence, in regions where CTTI is not possible, personal protection, public health control measures, and vaccination are indispensable for mitigating and exiting the COVID-19 pandemic.

Acute Foggy Corneal Epithelial Disease: Seeking Clinical Features and Risk Factors.

(1) Purpose: Here, we describe the clinical characteristics and predisposing factors of acute foggy corneal epithelial disease, a rare disease newly found during COVID-19 pandemic; (2) Methods: In this single-arm, ambispective case series study, ten patients with acute foggy corneal epithelial disease admitted between May 2020 and March 2021 were enrolled. Their detailed medical history and clinical and ophthalmic findings were recorded and analyzed; (3) Results: All the patients were female (100%), aged from 28 to 61 years (mean age of 40.4 ± 9.3 years). Seven cases (70%) had excessive eye use, and six cases (60%) had stayed up late and were overworked. Ten subjects (100%) presented with acute onset and a self-healing tendency. There was a mild-to-moderate decrease in the corrected visual acuity (0.35 ± 0.21 (LogMAR)). Slit-lamp examination showed diffuse dust-like opacity and edema in the epithelial layer of the cornea. By in vivo confocal microscope, epithelial cells presented characteristically a "relief-like" appearance. Anterior segment optical coherence tomography examination revealed that the mean epithelial thickness was increased (69.25 ± 4.31 µm, p < 0.01); (4) Conclusions: Acute foggy corneal epithelial disease is a rare disease in clinic, which tends to occur in young and middle-aged females. The typical clinical symptom is sudden foggy vision, which occurs repeatedly and can be relieved without treatment. Sex, an abnormal menstrual cycle, overuse of the eyes, fatigue and pressure might be risk factors. Changes in lifestyle and eye use habit during the COVID-19 pandemic may have possibly contributed to this disease incidence.

Long-term improvement of air quality associated with lung function benefits in Chinese young adults: A quasi-experiment cohort study.

INTRODUCTION: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear. OBJECTIVES: To examine whether the reduction of long-term air pollution was associated with lung function improvement among Chinese young adults. METHODS: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on air pollution concentrations were obtained from China Environmental Monitoring Station. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and forced expiratory flow at 50 % of FVC (FEF50%). We used linear mixed-effects model to examine the associations between the change of air pollutants concentrations and the change of lung function, and additional adjustments for indoor air pollution (IAP) source. We also conducted stratified analysis by sex. RESULTS: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4 ml, 321.5 ml, and 28.4 ml/s respectively in 2020. Every 5 µg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0 ml [95 % confidence interval (CI):6.0, 66.0 ml], 46.1 ml (95 % CI:16.7, 75.5 ml), and 124.2 ml/s (95 % CI:69.5, 178.9 ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. The estimated impact was almost unchanged after adjusting for IAP source. There was no significant effect difference between males and females. CONCLUSION: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.

RPpocket: An RNA-Protein Intuitive Database with RNA Pocket Topology Resources.

RNA-protein complexes regulate a variety of biological functions. Thus, it is essential to explore and visualize RNA-protein structural interaction features, especially pocket interactions. In this work, we develop an easy-to-use bioinformatics resource: RPpocket. This database provides RNA-protein complex interactions based on sequence, secondary structure, and pocket topology analysis. We extracted 793 pockets from 74 non-redundant RNA-protein structures. Then, we calculated the binding- and non-binding pocket topological properties and analyzed the binding mechanism of the RNA-protein complex. The results showed that the binding pockets were more extended than the non-binding pockets. We also found that long-range forces were the main interaction for RNA-protein recognition, while short-range forces strengthened and optimized the binding. RPpocket could facilitate RNA-protein engineering for biological or medical applications.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

Pathway of Cell Death and Its Role in Virus Infection.

The global pandemic of SARS-CoV-2 in the past 2 years has aroused great attention to infectious diseases, and emerging virus outbreaks have brought huge challenges to the global health system. Viruses are specific pathogens that completely rely on host cells for their own survival and disease transmission. At present, a growing number of studies have proved that inducing the death of virus-infected cells can prevent the spread of virus and promote disease recovery. Therefore, many ways to induce the death of infected cells are considered to be beneficial to host immunity. Cell death is a basic biological phenomenon. Programmed cell death (PCD), as an important part of the host's innate immune response, provides effective protection against virus transmission. Pyroptosis, apoptosis, and necroptosis are the most commonly studied pathways of PCD. Recent studies have found that three pathways of cell death can be activated during virus infection. More and more studies have shown the existence of extensive connections between PCDs, and this complex relationship is defined as PANoptosis, an inflammatory PCD pathway regulated by the PANoptosome complex, whose characteristics cannot be explained by any of the three PCD pathways. During viral infection, PANoptosis can promote inflammatory response by inducing the production of inflammatory cytokines and cell death to exert an antiviral mechanism. This article reviews the various effects of cell death pathways during viral infection and provides new ideas for clinical antiviral therapy and related immunotherapy.

Results Reporting and Early Termination of Childhood Obesity Trials Registered on ClinicalTrials.gov.

Objective: Childhood obesity is one of the most severe challenges of public health in the twenty-first century and may increase the risk of various physical and psychological diseases in adulthood. The prevalence and predictors of unreported results and premature termination in pediatric obesity research are not clear. We aimed to characterize childhood obesity trials registered on ClinicalTrials.gov and identify features associated with early termination and lack of results reporting. Methods: Records were downloaded and screened for all childhood obesity trials from the inception of ClinicalTrials.gov to July 29, 2021. We performed descriptive analyses of characteristics, Cox regression for early termination, and logistic regression for lack of results reporting. Results: We identified 1,312 trials registered at ClinicalTrials.gov. Among clinicalTrials.gov registered childhood obesity-related intervention trials, trial unreported results were 88.5 and 4.3% of trials were prematurely terminated. Additionally, the factors that reduced the risk of unreported outcomes were US-registered clinical studies and drug intervention trials. Factors associated with a reduced risk of early termination are National Institutes of Health (NIH) or other federal agency funding and large trials. Conclusion: The problem of unreported results in clinical trials of childhood obesity is serious. Therefore, timely bulletin of the results and reasons for termination remain urgent aims for childhood obesity trials.

Impact of Heat Inactivation of Blood Samples on Therapeutic Drug Monitoring of 5 Second-Generation Antipsychotics and Their Metabolites.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 outbreak has been classified as a pandemic. Because many coronaviruses are heat sensitive, heat inactivation of patient samples at 56°C before testing reduces the risk of transmission. The aim of this study is to assess the impact of heat inactivation of patient blood samples on plasma concentrations of 5 second-generation antipsychotics and their metabolites. METHODS: Blood samples were collected during routine clinical therapeutic drug monitoring examination between April 3, 2021, and April 19, 2021. Samples were divided into 2 groups: group A, noninactivated raw sample, and group B, inactivated samples. Inactivation was performed by a 30-minute incubation at 56°C. The levels of the 5 drugs and their metabolites before and after sample heat inactivation were measured using liquid chromatography-tandem mass spectrometry and compared. Furthermore, correlation and Bland-Altman analyses were conducted. RESULTS: No statistically significant difference was observed between the levels of the 5 drugs and their metabolites (ie, risperidone, 9-OH-risperidone, aripiprazole, dehydroaripiprazole, olanzapine, quetiapine, norquetiapine, clozapine, and norclozapine) in the noninactivated group A and the inactivated group B ( P > 0.05). Each drug's concentration values in inactivated and noninactivated treatments correlated (Spearman rs > 0.98; P < 0.001). The results of the noninactivated treatment methods and samples alone showed good consistency via Bland-Altman analysis. CONCLUSIONS: Blood sample heat inactivation had no significant effect on the therapeutic drug monitoring of 5 second-generation antipsychotics and their metabolites. This inactivated treatment method should be recommended to effectively protect laboratory staff from virus contamination.