Childhood-onset type 1 diabetes in Western Australia: An update on incidence and temporal trends from 2001 to 2022.

OBJECTIVE: To determine the incidence and incidence trends over 2001-2022 of childhood-onset type 1 diabetes (T1D) in Western Australia and assess the impact of the COVID-19 pandemic. METHODS: Children newly diagnosed with T1D aged 0-14 years in Western Australia from 1 January 2001 to 31 December 2022 were identified from the population-based Western Australian Children's Diabetes Database. Annual age- and sex-specific incidence was calculated, and Poisson regression was used to analyse trends by calendar year, month, sex and age group at diagnosis. Pandemic era impacts were also examined using the regression model adjusted for sex and age group. RESULTS: Between 2001 and 2022, 2311 children (1214 boys, 1097 girls) were newly diagnosed with T1D aged 0-14 years, giving an overall mean annual incidence of 22.9 per 100,000 person-years (95% CI: 22.0, 23.9), with no significant difference observed between boys and girls. A significant linear increasing trend was only observed in 10-14 year olds with boys and girls combined (1.2% per year [IRR 1.012 (95% CI: 1.002, 1.022)]). No significant difference in the incidence was observed between the pre- and post-pandemic period. CONCLUSIONS: The incidence of type 1 diabetes in 0-14 year old Western Australian children continues to increase in the oldest age group. Longer term monitoring of the incidence during the COVID-19 pandemic is needed to determine its impact on this globally unique population which experienced a delayed start to the pandemic with severe containment measures remaining in place until January 2022.

[Analysis of traditional Chinese medicine syndromes in patients with coronavirus disease 2019 in plateau areas].

OBJECTIVE: To analyze the distribution characteristics of traditional Chinese medicine (TCM) syndromes in patients with coronavirus disease 2019 (COVID-19) in plateau areas, and to provide theoretical basis for further clinical treatment of patients with COVID-19. METHODS: From August 9 to August 24, 2022, patients with COVID-19 admitted to the Third People's Hospital of Tibet Autonomous Region (designated hospital for COVID-19) were included, and their baseline characteristics (age, gender, source), clinical classification and distribution of TCM syndrome types were collected and analyzed. Data analysis was performed using SPSS 26.0 statistical software. RESULTS: A total of 161 COVID-19 patients were enrolled with ethnic distribution: 124 (77.02%) Tibetans, 35 (21.74%) Han, and 2 (1.24%) Hui, 68 males and 93 females. The male-to-female ratio was 0.73:1. Aged 1 to 94 years, the average age was (39.06±23.64) years old, of which 4 patients were under 1 year old (excluded because the information was missing). A total of 157 patients were enrolled, and 124 patients (78.9%) were under 60 years old, including 120 cases of common type, 4 cases of severe type, 0 cases of critical type, 7 cases over 80 years old, 1 case over 90 years old, and 32 cases under 18 years old. The clinical manifestations of the patient are mainly cough, expectoration, fever, aversion to cold, dry throat, headache, fatigue, running nose, dry mouth, bitter mouth, etc. Most of the tongue is pale, red, and white greasy moss or thin white coating. In TCM, the most common syndrome was cold-dampness blocking lung syndrome (99 cases, 63.06%), followed by cold-dampness stagnant lung syndrome (22 cases, 14.01%), damp-heat accumulating lung syndrome (22 cases, 14.01%), and humidity stagnant lung syndrome (11 cases, 7.01%). Syndromes of epidemic (2 cases, 1.27%), epidemic toxins blocking the lung pattern (1 cases, 0.64%), toxins with dryness intense heat in both qi and ying phases pattern (0 cases) accounted for less than 2%, and the distribution of various syndrome types in COVID-19 patients was uneven (χ 2 = 0.48, P < 0.05). CONCLUSIONS: The most common TCM syndromes of COVID-19 patients in Lhasa are cold-dampness blocking lung syndrome, followed by cold-dampness stagnant lung syndrome, damp-heat accumulating lung syndrome, and humidity stagnant lung syndrome.

CovInter: interaction data between coronavirus RNAs and host proteins.

Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the 'molecular arms race' between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/.

COVID-19 Vaccination is Associated With Favorable Outcomes Among Lung Transplant Patients With Breakthrough Infections.

BACKGROUND: There are limited data regarding the clinical efficacy of COVID-19 vaccines among lung transplant (LT) patients. METHODS: We included all LT patients diagnosed with COVID-19 between March 1, 2020, and December 10, 2021 (n = 84; median age 55, range, 20-73 years; males 65.5%). The study group was divided into 3 groups based on the vaccination status (patients who did not complete the primary series for any of the vaccines: n = 58; those with 2 doses of messenger RNA (mRNA) or 1 dose of the adenoviral vector vaccine, vaccinated group: n = 16; those with at least 1 additional dose beyond the primary series, boosted group: n = 10). RESULTS: Pulmonary parenchymal involvement on chest computed tomography scan was less common among the boosted group (P = .009). The proportion of patients with new or worsening respiratory failure was significantly lower among the vaccinated and boosted groups and these patients were significantly more likely to achieve the composite endpoint of oxygen-dependence free survival (P = .02). On multivariate logistic regression analysis, higher body mass index, restrictive lung disease as the transplant indication, and preinfection chronic lung allograft dysfunction were independently associated with acute or acute on chronic respiratory failure while being on therapeutic dose anticoagulation and having received the booster dose had a protective effect. CONCLUSION: COVID-19 vaccines appear to have several favorable effects among LT patients with breakthrough infections including lower likelihood of allograft involvement on imaging (among boosted patients), need of hospitalization, and complications such as new or worsening respiratory failure.

A Facile Single-Phase-Fluid-Driven Bubble Microfluidic Generator for Potential Detection of Viruses Suspended in Air

Microfluidics devices have widely been employed to prepare monodispersed microbubbles/droplets, which have promising applications in biomedical engineering, biosensor detection, drug delivery, etc. However, the current reported microfluidic devices need to control at least two-phase fluids to make microbubbles/droplets. Additionally, it seems to be difficult to make monodispersed microbubbles from the ambient air using currently reported microfluidic structures. Here, we present a facile approach to making monodispersed microbubbles directly from the ambient air by driving single-phase fluid. The reported single-phase-fluid microfluidic (SPFM) device has a typical co-flow structure, while the adjacent space between the injection tube and the collection tube is open to the air. The flow condition inside the SPFM device was systematically studied. By adjusting the flow rate of the single-phase fluid, bubbles were generated, the sizes of which could be tuned precisely. This facile bubble generator may have significant potential as a detection sensor in detecting viruses in spread droplets or haze particles in ambient air.

Predictors and outcomes of respiratory failure among lung transplant patients with COVID-19.

BACKGROUND: There is limited data on the predictors and outcomes of new or worsening respiratory failure among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). METHODS: We included all the LT patients diagnosed with COVID-19 during a 1-year period (March 2020 to February 2021; n = 54; median age: 60, 20-73 years; M:F 37:17). Development of new or worsening respiratory failure (ARF) was the primary outcome variable. RESULTS: The overall incidence of ARF was 48.1% (n = 26). More than 20% of patients (n = 11) needed intubation and mechanical ventilation. Body mass index > 25 Kg/m2 (adjusted OR: 5.7, .99-32.93; P = .05) and peak D-dimer levels > .95 mcg/ml (adjusted OR: 24.99, 1.77-353.8; P = .017) were independently associated with ARF while anticoagulation use prior to COVID-19 was protective (adjusted OR: .024, .001-.55; P = .02). Majority patients survived the acute illness (85.2%). Pre-infection chronic lung allograft dysfunction (CLAD) was an independent predictor of mortality (adjusted HR: 5.03, 1.14-22.25; P = .033). CONCLUSIONS: COVID-19 is associated with significant morbidity and mortality among LT patients. Patients on chronic anticoagulation seem to enjoy favorable outcomes, while higher BMI and peak D-dimer levels are associated with development of ARF. Pre-infection CLAD is associated with an increased risk of death from COVID-19.

Banks as Lenders of First Resort: Evidence from the COVID-19 Crisis

In March of 2020, banks faced the largest increase in liquidity demands ever observed. Firms drew funds on a massive scale from pre-existing credit lines and loan commitments in anticipation of cash flow disruptions from the economic shutdown designed to contain the COVID-19 crisis. The increase in liquidity demands was concentrated at the largest banks, who serve the largest firms. Pre-crisis financial condition did not limit banks’ liquidity supply. Coincident inflows of funds to banks from both the Federal Reserve’s liquidity injection programs and from depositors, along with strong pre-shock bank capital, explain why banks were able to accommodate these liquidity demands.

Post-infection pulmonary sequelae after COVID-19 among patients with lung transplantation.

BACKGROUND: There is limited data on outcomes among lung transplant (LT) patients who survive Coronavirus disease 2019 (COVID-19). METHODS: Any single or bilateral LT patients who tested positive for SARS-CoV-2 between March 1, 2020, to February 15, 2021 (n = 54) and survived the acute illness were included (final n = 44). Each patient completed at least 3 months of follow-up (median: 4.5; range 3-12 months) after their index hospitalization for COVID-19. The primary endpoint was a significant loss of lung functions (defined as > 10% decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1 ) on two spirometries, at least 3 weeks apart compared to the pre-infection baseline). RESULTS: A majority of the COVID-19 survivors had persistent parenchymal opacities (n = 29, 65.9%) on post-infection CT chest. Patients had significantly impaired functional status, with the majority reporting residual disabilities (Karnofsky performance scale score of 70% or worse; n = 32, 72.7%). A significant loss of lung function was observed among 18 patients (40.9%). Three patients met the criteria for new chronic lung allograft dysfunction (CLAD) following COVID-19 (5.6%), with all three demonstrating restrictive allograft syndrome phenotype. An absolute lymphocyte count < 0.6 × 103 /dl and ferritin > 150 ng/ml at the time of hospital discharge was independently associated with significant lung function loss. CONCLUSIONS: A significant proportion of COVID-19 survivors suffer persistent allograft injury. Low absolute lymphocyte counts (ALC) and elevated ferritin levels at the conclusion of the hospital course may provide useful prognostic information and form the basis of a customized strategy for ongoing monitoring and management of allograft dysfunction. TWEET: Twitter handle: @AmitBangaMD Lung transplant patients who survive COVID-19 suffer significant morbidity with persistent pulmonary opacities, loss of lung functions, and functional deficits. Residual elevation of the inflammatory markers is predictive.

RNA-RNA interactions between SARS-CoV-2 and host benefit viral development and evolution during COVID-19 infection.

Some studies reported that genomic RNA of SARS-CoV-2 can absorb a few host miRNAs that regulate immune-related genes and then deprive their function. In this perspective, we conjecture that the absorption of the SARS-CoV-2 genome to host miRNAs is not a coincidence, which may be an indispensable approach leading to viral survival and development in host. In our study, we collected five datasets of miRNAs that were predicted to interact with the genome of SARS-CoV-2. The targets of these miRNAs in the five groups were consistently enriched immune-related pathways and virus-infectious diseases. Interestingly, the five datasets shared no one miRNA but their targets shared 168 genes. The signaling pathway enrichment of 168 shared targets implied an unbalanced immune response that the most of interleukin signaling pathways and none of the interferon signaling pathways were significantly different. Protein-protein interaction (PPI) network using the shared targets showed that PPI pairs, including IL6-IL6R, were related to the process of SARS-CoV-2 infection and pathogenesis. In addition, we found that SARS-CoV-2 absorption to host miRNA could benefit two popular mutant strains for more infectivity and pathogenicity. Conclusively, our results suggest that genomic RNA absorption to host miRNAs may be a vital approach by which SARS-CoV-2 disturbs the host immune system and infects host cells.

Predictive Value of Eosinophil Count on COVID-19 Disease Progression and Outcomes, a Retrospective Study of Leishenshan Hospital in Wuhan, China.

BACKGROUND: The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19. METHODS: A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death. RESULTS: Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively. CONCLUSION: Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

The miRNA: a small but powerful RNA for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe and rapidly evolving epidemic. Now, although a few drugs and vaccines have been proved for its treatment and prevention, little systematic comments are made to explain its susceptibility to humans. A few scattered studies used bioinformatics methods to explore the role of microRNA (miRNA) in COVID-19 infection. Combining these timely reports and previous studies about virus and miRNA, we comb through the available clues and seemingly make the perspective reasonable that the COVID-19 cleverly exploits the interplay between the small miRNA and other biomolecules to avoid being effectively recognized and attacked from host immune protection as well to deactivate functional genes that are crucial for immune system. In detail, SARS-CoV-2 can be regarded as a sponge to adsorb host immune-related miRNA, which forces host fall into dysfunction status of immune system. Besides, SARS-CoV-2 encodes its own miRNAs, which can enter host cell and are not perceived by the host's immune system, subsequently targeting host function genes to cause illnesses. Therefore, this article presents a reasonable viewpoint that the miRNA-based interplays between the host and SARS-CoV-2 may be the primary cause that SARS-CoV-2 accesses and attacks the host cells.

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates (preprint)

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

Serverless computing for cloud-based power grid emergency generation dispatch

Operating a modern power grid reliably in case of SCADA/EMS failure or amid difficult times like COVID-19 pandemic is a challenging task for grid operators. In [11], a PMU-based emergency generation dispatch scheme has been proposed to help the system operators with the supply and demand balancing;however, its realization highly relies on the control center infrastructure for computing and communication. This work, rather than using the on-premises server and dispatch communication system, proposes and implements a cloud-centric serverless architecture to ensure the operation continuity regardless of local infrastructure's availability and accessibility. Through its prototype implementation and evaluation at ISO New England, the solution has demonstrated two major advantages. Firstly, the cloud infrastructure is independent and fault-tolerant, providing grid monitoring and control capability even when EMS loses the corresponding functionality or when operators need to work remotely away from the control center. Secondly, the overall design is event-driven using serverless cloud services in response to the SCADA/EMS failure event. Thanks to “serverless”, the burden of the server provisioning and maintenance can be avoided from the user side. The cost of using public cloud services for this solution is extremely low since it is architected and implemented based on the event-driven Function-as-a-Service (FaaS) model. This work also develops a comprehensive cyber security mechanism to comply with critical infrastructure requirements for the power grid, which can serve as an exemplary framework for other grid operators to secure their cloud services.

Banks as Lenders of First Resort: Evidence from the COVID-19 Crisis

In March 2020, banks faced the largest increase in liquidity demands ever observed. Firms drew funds on a massive scale from preexisting credit lines in anticipation of cash flow and financial disruptions stemming from the advent of the COVID-19 crisis. The increase in liquidity demands was concentrated at the largest banks, who serve the largest firms. Precrisis financial condition did not constrain large banks’ liquidity supply. Coincident inflows of funds from both the Federal Reserve’s liquidity injection programs and depositors, along with strong preshock bank capital, explain why banks were able to accommodate these liquidity demands.