Heart failure after dengue infection- a population-based self-controlled case-series study.

BACKGROUND: Major cardiovascular events (MACEs) have been described with dengue infection. Among these MACEs, heart failure (HF) is the most common but has not been thoroughly assessed. This study aimed to evaluate the association between dengue and HF. METHODS: Under the self-controlled case-series study design, we used the Notifiable Infectious Disease dataset linkage with the National Health Insurance claims data to obtain the study subjects. All laboratory-confirmed dengue cases who were hospitalized for HF after dengue infection within one year between 2009 and 2015 in Taiwan were included. We identified the first 7 and 14 days after dengue infection as the risk intervals. The incidence rate ratio (IRR) and 95% confidence interval (CI) for HF were estimated by conditional Poisson regression. RESULTS: Among the 65,906 dengue patients, 230 had admission for HF after dengue infection within one year. The IRR of HF admission within the first week after dengue infection was 56.50 (95% C.I. 43.88-72.75). This risk was highest in >60 years (IRR = 59.32, 95% C.I. 45.43-77.43) and lower in 0-40 years (IRR = 25.82, 95% C.I. 2.89-231.02). The risk was nearly nine times higher among admission (for dengue infection) than among nonadmission cases (IRR 75.35 vs. 8.61, p < 0.0001). The risks increased slightly in the second week 8.55 and became less obvious after the third and fourth week. CONCLUSIONS: Patients with dengue infection have a risk of developing acute heart failure within one week, especially in >60 years, men, and dengue admission subjects. The findings emphasize the awareness of diagnosis and further appropriate treatment of HF.

Immunogenicity and safety of heterologous mRNA-1273/MVC-COV1901 vaccination versus homologous mRNA1273 vaccination: A randomized, double-blind controlled study.

BACKGROUND/PURPOSE: MVC-COV1901 is a protein vaccine based on the same SARS-CoV-2 strain used in mRNA vaccine mRNA-1273. Data are lacking on immunogenicity and safety of MVC-COV1901 as heterologous boost for people already received one dose of mRNA-1273. METHODS: This is a randomized, double-blind trial that recruited adults aged 20-70 years who previously received a single dose of mRNA-1273 vaccine and were randomly assigned in a 1:1 ratio to receive a second dose with the homologous vaccine or protein-based MVC-COV1901 8-12 weeks after the first dose. The primary outcome was neutralizing antibody titers in terms of the geometric mean titer (GMT) 14 days after the second dose. Safety was assessed in all participants who received a dose of the study vaccine. The study is registered with ClinicalTrials.gov (NCT05079633). RESULTS: From September 30 to November 5, 2021, 144 participants were enrolled and randomly assigned to the MVC-COV1901 boost group (n = 72) or the mRNA-1273 boost group (n = 72). The neutralizing antibodies on Day 15 and the anti-SARS-CoV-2 IgG titers on Day 15 and 29 of homologous mRNA-1273 were significantly higher than those of heterologous mRNA-1273/MVC-COV1901. Cellular immune responses were comparable in both groups. However, adverse events were much more frequent after the mRNA-1273 boost than after the MVC-COV1901 boost. CONCLUSION: Our results show that heterologous boost with MVC-COV1901 yielded an inferior immunogenicity but significantly fewer adverse events, compared with homologous boost with mRNA-1273. In people experienced severe adverse events after prime dose of mRNA-1273, as well as in periods when the supply of mRNA-1273 is limited, MVC-COV1901 could serve as an acceptable alternative heterologous boost.

Predicting Demands of COVID-19 Prevention and Control Materials via Co-Evolutionary Transfer Learning.

The novel coronavirus pneumonia (COVID-19) has created great demands for medical resources. Determining these demands timely and accurately is critically important for the prevention and control of the pandemic. However, even if the infection rate has been estimated, the demands of many medical materials are still difficult to estimate due to their complex relationships with the infection rate and insufficient historical data. To alleviate the difficulties, we propose a co-evolutionary transfer learning (CETL) method for predicting the demands of a set of medical materials, which is important in COVID-19 prevention and control. CETL reuses material demand knowledge not only from other epidemics, such as severe acute respiratory syndrome (SARS) and bird flu but also from natural and manmade disasters. The knowledge or data of these related tasks can also be relatively few and imbalanced. In CETL, each prediction task is implemented by a fuzzy deep contractive autoencoder (CAE), and all prediction networks are cooperatively evolved, simultaneously using intrapopulation evolution to learn task-specific knowledge in each domain and using interpopulation evolution to learn common knowledge shared across the domains. Experimental results show that CETL achieves high prediction accuracies compared to selected state-of-the-art transfer learning and multitask learning models on datasets during two stages of COVID-19 spreading in China.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Forward-backward and period doubling bifurcations in a discrete epidemic model with vaccination and limited medical resources.

A discrete epidemic model with vaccination and limited medical resources is proposed to understand its underlying dynamics. The model induces a nonsmooth two dimensional map that exhibits a surprising array of dynamical behavior including the phenomena of the forward-backward bifurcation and period doubling route to chaos with feasible parameters in an invariant region. We demonstrate, among other things, that the model generates the above described phenomena as the transmission rate or the basic reproduction number of the disease gradually increases provided that the immunization rate is low, the vaccine failure rate is high and the medical resources are limited. Finally, the numerical simulations are provided to illustrate our main results.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

Impact of Taiwan's 2021 COVID-19 lockdown on the symptom severity and quality of life of patients with narcolepsy.

COVID-19 lockdowns can influence the sleep quality and daytime condition of patients with narcolepsy. Using data from our cohort study, we investigated changes in the quality of life and the symptom severity of patients with narcolepsy during Taiwan's 2021 lockdown and investigated differences by narcolepsy subtype, sex, and age. Patients with type 1 and type 2 narcolepsy (NT1 and NT2, respectively) aged 6-40 years were retrospectively recruited from our narcolepsy cohort study. These patients were regularly evaluated using the Short Form 36 Health Survey questionnaire (SF-36), the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy and sleep diary. We compared the differences between the lockdown and the prelockdown periods by narcolepsy subtype, sex, and age. We used a paired t test analysis to compare differences in the SF-36, ESS, VAS scores and data of sleep diary between the prelockdown and lockdown periods (p1), and an independent t test analysis was used to compare the changes in different subgroups between the prelockdown and lockdown periods (p2). A total of 120 patients with narcolepsy were recruited (mean age 24.22 ± 6.87 years; 58% male); 80 of the patients had NT1 (mean age 25.25 ± 6.79 years; 60% male) and 40 had NT2 (mean age 22.16 ± 6.64, 53% male). During the lockdown period, the ESS score of total patients was decreased (p = 0.039) and body mass index was increased (p = 0.02). The NT1 group decreased significantly (p1 = 0.017), especially in men (p1 = 0.016) and adults (p1 = 0.04); scores for the VT domain of the SF-36 increased significantly in male and adult patients with NT2 (p1 = 0.048 and 0.012). Additionally, male patients with NT2 exhibited significantly decreased scores in the physical and emotional role functioning domains (p1 = 0.028, 0.024). The children and adolescents with NT1 had significantly decreased scores in the general health domain of the SF-36, but no significant change was noted in that of adults (p1 = 0.027, p2 = 0.012). We observed both negative and positive impacts of Taiwan's 2021 lockdown on patients with narcolepsy. A more flexible but structured daily routine with adequate sleep time should be considered for this population during lockdown and nonlockdown periods.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis

Background Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). Method We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody > 0.8 U/mL and interferon-γ > 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. Result PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. Conclusions Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSIONS: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Diagnostic accuracy of eHealth literacy measurement tools in older adults: a systematic review.

BACKGROUND: In Canada, virtual health care rapidly expanded during the COVID-19 pandemic. There is substantial variability between older adults in terms of digital literacy skills, which precludes equitable participation of some older adults in virtual care. Little is known about how to measure older adults' electronic health (eHealth) literacy, which could help healthcare providers to support older adults in accessing virtual care. Our study objective was to examine the diagnostic accuracy of eHealth literacy tools in older adults. METHODS: We completed a systematic review examining the validity of eHealth literacy tools compared to a reference standard or another tool. We searched MEDLINE, EMBASE, CENTRAL/CDSR, PsycINFO and grey literature for articles published from inception until January 13, 2021. We included studies where the mean population age was at least 60 years old. Two reviewers independently completed article screening, data abstraction, and risk of bias assessment using the Quality Assessment for Diagnostic Accuracy Studies-2 tool. We implemented the PROGRESS-Plus framework to describe the reporting of social determinants of health. RESULTS: We identified 14,940 citations and included two studies. Included studies described three methods for assessing eHealth literacy: computer simulation, eHealth Literacy Scale (eHEALS), and Transactional Model of eHealth Literacy (TMeHL). eHEALS correlated moderately with participants' computer simulation performance (r = 0.34) and TMeHL correlated moderately to highly with eHEALS (r = 0.47-0.66). Using the PROGRESS-Plus framework, we identified shortcomings in the reporting of study participants' social determinants of health, including social capital and time-dependent relationships. CONCLUSIONS: We found two tools to support clinicians in identifying older adults' eHealth literacy. However, given the shortcomings highlighted in the validation of eHealth literacy tools in older adults, future primary research describing the diagnostic accuracy of tools for measuring eHealth literacy in this population and how social determinants of health impact the assessment of eHealth literacy is needed to strengthen tool implementation in clinical practice. PROTOCOL REGISTRATION: We registered our systematic review of the literature a priori with PROSPERO (CRD42021238365).

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

In Vitro Susceptibilities of Worldwide Isolates of Intrapulmonary Aspergillus Species and Important Candida Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017-2020.

To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to explore in vitro antifungal susceptibilities against clinically important isolates of Aspergillus and Candida species (collected from intrapulmonary and sterile body areas, respectively). We applied the CLSI antifungal 2020 and the EUCAST antifungal 2020 guidelines. From 2017 to 2020, isolates of intrapulmonary Aspergillus fumigatus (n = 660), Aspergillus niger (n = 107), Aspergillus flavus (n = 96), Aspergillus terreus (n = 40), and Aspergillus nidulans species complex (n = 26) and sterile site-originated isolates of Candida albicans (n = 1,810), Candida glabrata (n = 894), Candida krusei (n = 120), Candida dubliniensis (n = 107), Candida lusitaniae (n = 82), Candida guilliermondii (n = 28), and Candida auris (n = 7) were enrolled in this study. Using the EUCAST 2020 breakpoints, it was demonstrated that amphotericin B and posaconazole displayed poor in vitro susceptibility rates against A. fumigatus isolates (<50% and 18.9%, respectively). In contrast, isavuconazole and itraconazole showed high in vitro potency against most Aspergillus isolates (>92%). Most intrapulmonary Aspergillus isolates exhibited MICs of ≤0.06 µg/mL to anidulafungin. Furthermore, intrapulmonary A. fumigatus isolates collected from Italy and the United Kingdom exhibited lower in vitro susceptibility to isavuconazole (72.2% and 69%, respectively) than those in the remaining ATLAS participant countries (>85%). Higher isavuconazole MIC90s against C. auris and C. guilliermondii (1 and 4 µg/mL, respectively) were observed compared to the other five Candida species. Despite the aforementioned MICs and susceptibilities against fungi, research needs to consider the pharmacokinetic (PK) profiles, pharmacodynamic (PD) parameters, and clinical treatment experience with antifungals against specific Aspergillus species. IMPORTANCE In addition to monitoring the antifungal susceptibilities of clinically important fungi, reviewing the PK/PD indices and the clinical therapy experience of antifungals under evaluation are important to guide an appropriate antifungal prescription. The efficacies of liposomal amphotericin B complex and anidulafungin for the treatment of pulmonary aspergillosis caused by different Aspergillus species need to be periodically evaluated in the future.

Does Same-Sex Marriage Legalization Make Gay Men Want to Have Children? Findings from a Panel Study in Taiwan

Introduction This study capitalized on prospective legal change in Taiwan to capture changes in gay men's desires and attitudes toward parenthood as a function of the legalization of same-sex marriage (SSM). Methods A panel of 731 gay men (mean age = 26.8 years ± 5.81) completed an online survey between 2019 and 2020, shortly before and 1½ years after the legalization of SSM, to report their parenting desire, marital status, and attitudes toward parenthood and marriage. Results This study found that fewer participants in the follow-up survey expressed a parenting desire (59.0% vs. 74.2%), and the perceived importance of parenthood dropped mildly (3.48 to 3.26, Cohen's d = 0.269). Those who expressed a consistent parenting desire attached greater importance to SSM. The perceived importance of SSM was modestly and positively related to the perceived importance of having a child. Conclusion Although the decrease in parenting desire and its perceived importance may be attributable to a lack of access to family-building options (e.g., surrogacy and adoption) and the COVID-19 pandemic, our findings illustrate that parenthood might become a next step for some Taiwanese male same-sex couples who married or considered marriage. Policy Implications The study findings provide information for policymakers to gauge the possible number of sexual minority men who might want to have a child and consider resource allocation and deliberation on policy changes related to reproduction.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS.

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Deep learning attention-guided radiomics for COVID-19 chest radiograph classification.

Background: Accurate assessment of coronavirus disease 2019 (COVID-19) lung involvement through chest radiograph plays an important role in effective management of the infection. This study aims to develop a two-step feature merging method to integrate image features from deep learning and radiomics to differentiate COVID-19, non-COVID-19 pneumonia and normal chest radiographs (CXR). Methods: In this study, a deformable convolutional neural network (deformable CNN) was developed and used as a feature extractor to obtain 1,024-dimensional deep learning latent representation (DLR) features. Then 1,069-dimensional radiomics features were extracted from the region of interest (ROI) guided by deformable CNN's attention. The two feature sets were concatenated to generate a merged feature set for classification. For comparative experiments, the same process has been applied to the DLR-only feature set for verifying the effectiveness of feature concatenation. Results: Using the merged feature set resulted in an overall average accuracy of 91.0% for three-class classification, representing a statistically significant improvement of 0.6% compared to the DLR-only classification. The recall and precision of classification into the COVID-19 class were 0.926 and 0.976, respectively. The feature merging method was shown to significantly improve the classification performance as compared to using only deep learning features, regardless of choice of classifier (P value <0.0001). Three classes' F1-score were 0.892, 0.890, and 0.950 correspondingly (i.e., normal, non-COVID-19 pneumonia, COVID-19). Conclusions: A two-step COVID-19 classification framework integrating information from both DLR and radiomics features (guided by deep learning attention mechanism) has been developed. The proposed feature merging method has been shown to improve the performance of chest radiograph classification as compared to the case of using only deep learning features.