Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro).

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (Mpro) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 Mpro inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior inhibitory activity against SARS-CoV-2 Mpro relative to baicalein (IC50 = 0.085 ± 0.006 and 0.966 ± 0.065 µM, respectively), as well as improved physicochemical and drug metabolism and pharmacokinetics (DMPK) properties. In addition, C7 inhibits viral replication in SARS-CoV-2-infected Vero E6 cells more effectively than baicalein (EC50 = 1.10 ± 0.12 and 5.15 ± 1.64 µM, respectively) with low cytotoxicity (CC50 ＞ 50 µM). An X-ray co-crystal structure reveals a non-covalent mechanism of action, and a noncanonical binding mode not observed by baicalein. These results suggest that C7 represents a promising lead for development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 drugs.

Willingness to Undergo Gastroscopy for Early Gastric Cancer Screening and Its Associated Factors During the COVID-19 Pandemic - A Nationwide Cross-Sectional Study in China.

Purpose: This study aimed to investigate the willingness of Chinese adults aged 40 years and older to undergo gastroscopy for gastric cancer (GC) screening during the COVID-19 pandemic in 2020. The secondary purpose was to identify factors influencing willingness to undergo gastroscopy. Methods: A cross-sectional questionnaire survey was conducted in selected cities and counties from nine provinces in China using a multi-stage sampling approach. A multivariate logistic regression model was used to determine the independent predictors of willingness to undergo gastroscopy. Results: This study included 1900 participants, and 1462 (76.95%) responded that they would undergo gastroscopy for GC screening. Participants of younger age, from the eastern region, living in an urban area, with higher educational levels, with Helicobacter pylori (H. pylori) infection, or with precancerous stomach lesions, were more willing to undergo gastroscopy. The top four reasons to reject gastroscopy were fear of pain or discomfort, worry about a possible devastating test result, no symptoms in self-feeling, and concern about the high expense. Of all those who would reject gastroscopy for GC screening, 36.76% (161/438) would be willing to accept painless gastroscopy, while 24.89% (109/438) would be willing to undergo gastroscopy screening if higher medical reimbursement rates were available. Participants considered that gastroscopy was a relatively fearful and unknown procedure, accompanied by high risks and benefits compared to all other life events. Conclusion: In general, 76.95% of participants over 40 years old were willing to undergo gastroscopy for GC screening in China during the COVID-19 pandemic. Participants' willingness to undergo GC screening increased due to medical resource constraints and increased interest in their health. Individuals with H. pylori infection are more likely to undergo gastroscopy, whereas old age individuals, those with lower educational levels, and those living in rural areas are more likely to reject gastroscopy.

A new and specific automated blood pressure device for exercise stress testing.

Blood pressure (BP) measurement plays a critical role in cardiac stress testing and is most commonly assessed manually. The emphasis of social distancing during the COVID-19 pandemic has renewed the interest in and the need for an automated BP device for incremental exercise stress testing. We assessed the accuracy of a new automated blood pressure device specifically manufactured for cardiac stress testing. Thirty-five adults aged 35 ± 16 years were studied during an incremental stress test on the cycle ergometer. Three observers measured BP simultaneously, two listening to Korotkoff sounds using a dual-headed stethoscope and one using headphones to listen to sounds generated by an automated BP device. With increasing workload, systolic BP increased progressively without significant differences in BP readings between any observer compared with the automated monitor at any stage during exercise. Systolic BP obtained with the BP machine was strongly correlated with those obtained by the stethoscope observers (r = 0.96) and the observer with headphones (r = 0.95). Diastolic BP obtained with the BP machine was moderately and significantly associated with those obtained by the stethoscope observers (r = 0.75) and the observer with headphones (r = 0.75). The automated BP monitor specifically made for cardiac stress testing accurately measured both systolic and diastolic blood pressure during exercise.

Resilience mediates the association between alexithymia and stress in Chinese medical students during the COVID-19 pandemic.

Background: Evidence indicates that medical students have had high rates of mental health problems, especially during the COVID-19 pandemic, which could be affected by alexithymia-a marked dysfunction in emotional awareness, social attachment and interpersonal relationships-and stress. However, psychological resilience might relieve alexithymia and stress levels. Aims: This study aimed to investigate the role of resilience in alexithymia and stress in medical students. Methods: A total of 470 medical students completed online and offline surveys, including the Toronto Alexithymia Scale-20 (TAS-20), the Connor-Davidson Resilience Scale (CD-RISC) and the College Student Stress Questionnaire (CSSQ). The data of five participants were excluded because of a lack of integrity. Mann-Whitney U test or Kruskal-Wallis test was used to compare group differences in the CD-RISC scores among categorical variables. Spearman correlation analysis was employed to evaluate the associations between resilience and alexithymia and between resilience and stress. Mediation analysis was used to test the mediating effect of resilience between alexithymia and stress. Results: Of the medical students considered in the analysis, 382 (81.28%) were female and 88 (18.72%) were male. There was a significant negative correlation between the TAS-20 scores and the total and subtotal CD-RISC scores (p<0.001). The CSSQ scores also significantly negatively correlated with the total and subtotal CD-RISC scores (p<0.001). Resilience mediated the relationship between alexithymia and stress (total effect=1.044 7, p<0.001). The indirect effect of alexithymia significantly impacted stress through resilience (effect=0.167 0, 95% CI: 0.069 to 0.281). Conclusions: Our findings suggest that resilience might effectively reduce alexithymia and stress. They also contributed to a better understanding of the mediating effects of resilience on alexithymia and stress during the COVID-19 pandemic. The evidence from these results encourages universities to focus on improving students' resilience.

Resilience mediates the association between alexithymia and stress in Chinese medical students during the COVID-19 pandemic

Background Evidence indicates that medical students have had high rates of mental health problems, especially during the COVID-19 pandemic, which could be affected by alexithymia—a marked dysfunction in emotional awareness, social attachment and interpersonal relationships—and stress. However, psychological resilience might relieve alexithymia and stress levels. Aims This study aimed to investigate the role of resilience in alexithymia and stress in medical students. Methods A total of 470 medical students completed online and offline surveys, including the Toronto Alexithymia Scale-20 (TAS-20), the Connor-Davidson Resilience Scale (CD-RISC) and the College Student Stress Questionnaire (CSSQ). The data of five participants were excluded because of a lack of integrity. Mann-Whitney U test or Kruskal-Wallis test was used to compare group differences in the CD-RISC scores among categorical variables. Spearman correlation analysis was employed to evaluate the associations between resilience and alexithymia and between resilience and stress. Mediation analysis was used to test the mediating effect of resilience between alexithymia and stress. Results Of the medical students considered in the analysis, 382 (81.28%) were female and 88 (18.72%) were male. There was a significant negative correlation between the TAS-20 scores and the total and subtotal CD-RISC scores (p<0.001). The CSSQ scores also significantly negatively correlated with the total and subtotal CD-RISC scores (p<0.001). Resilience mediated the relationship between alexithymia and stress (total effect=1.044 7, p<0.001). The indirect effect of alexithymia significantly impacted stress through resilience (effect=0.167 0, 95% CI: 0.069 to 0.281). Conclusions Our findings suggest that resilience might effectively reduce alexithymia and stress. They also contributed to a better understanding of the mediating effects of resilience on alexithymia and stress during the COVID-19 pandemic. The evidence from these results encourages universities to focus on improving students' resilience.

Feasibility and Performance of Hemoglobin A1C Self-Testing During COVID-19 Among African Americans With Type 2 Diabetes.

PURPOSE: The purpose of the study was to determine the feasibility of implementing A1C self-testing at home using the A1CNow® Self Check and to compare the accuracy of the A1CNow to a reference standard in African Americans with type 2 diabetes (T2D). METHODS: African American adults with T2D were recruited from 13 different churches (N = 123). Phase 1, conducted during the early phase of the COVID-19 pandemic, examined the feasibility of A1C assessment using the A1CNow performed at home by untrained participants. Phase 2, conducted when in-person research resumed, compared A1C values concurrently measured using the A1CNow and the DCA Vantage™ Analyzer (reference standard) collected by research staff at church testing sites. RESULTS: In Phase 1, 98.8% of participants successfully completed at least 1 at-home A1C test; the overall failure rate was 24.7%. In Phase 2, the failure rate of staff-performed A1CNow testing was 4.4%. The Bland-Altman plot reveals that A1CNow values were 0.68% lower than DCA values, and the mean differences (A1CNow minus DCA) ranged from -2.6% to 1.2% with a limit of agreement between -1.9% to 0.5%. CONCLUSIONS: A1C self-testing is feasible for use in community settings involving African American adults with T2D. The A1CNow Self-Check underestimated A1C values when compared with the reference standard. Ongoing improvements in point-of-care devices have the potential to expand research and clinical care, especially in underserved communities.

Summary report of seven cases of COVID-19 infection in renal transplant recipients.

The coronavirus disease 2019 (COVID-19) has swept the world, posing a serious threat to people's lives and health. Several cases of COVID-19 infection in renal transplant recipients (RTRs) have been reported, but the treatment and prognosis have not been fully elucidated. We followed-up with RTRs infected with SARS-CoV2 in our center and classified them as five clinical types-asymptomatic, mild, moderate, severe, and critical. The immunosuppressive agents were not adjusted in asymptomatic carriers and mild patients, the former was mainly treated by isolation, and the latter was treated by low-dose intravenous immunoglobulin (IVIG) to enhance immunity. For moderate or severe patients, the immunosuppressive agents were largely reduced or even interrupted, low-dose IVIG was adopted, and low-dose methylprednisolone (MP) was used to inhibit inflammation and rejection. Immunosuppressants were discontinued early in critical patients; IVIG, high-dose MP, and antibiotics were used. Meanwhile, all patients received at least one antiviral drugs. After aggressive treatment, three patients developed acute kidney injury, and two showed reversal, while the remaining one lost the allograft kidney; one patient died, while other patients were discharged. For different clinical types of RTRs infected with COVID-19, personalized therapies were essential, Meanwhile, patients with COVID-19 infection may have different outcomes due to their different clinical manifestations.

DUDA-Net: a double U-shaped dilated attention network for automatic infection area segmentation in COVID-19 lung CT images.

PURPOSE: The global health crisis caused by coronavirus disease 2019 (COVID-19) is a common threat facing all humankind. In the process of diagnosing COVID-19 and treating patients, automatic COVID-19 lesion segmentation from computed tomography images helps doctors and patients intuitively understand lung infection. To effectively quantify lung infections, a convolutional neural network for automatic lung infection segmentation based on deep learning is proposed. METHOD: This new type of COVID-19 lesion segmentation network is based on a U-Net backbone. First, a coarse segmentation network is constructed to extract the lung areas. Second, in the encoding and decoding process of the fine segmentation network, a new soft attention mechanism, namely the dilated convolutional attention (DCA) mechanism, is introduced to enable the network to focus on better quantitative information to strengthen the network's segmentation ability in the subtle areas of the lesions. RESULTS: The experimental results show that the average Dice similarity coefficient (DSC), sensitivity (SEN), specificity (SPE) and area under the curve of DUDA-Net are 87.06%, 90.85%, 99.59% and 0.965, respectively. In addition, the introduction of a cascade U-shaped network scheme and DCA mechanism can improve the DSC by 24.46% and 14.33%, respectively. CONCLUSION: The proposed DUDA-Net approach can automatically segment COVID-19 lesions with excellent performance, which indicates that the proposed method is of great clinical significance. In addition, the introduction of a coarse segmentation network and DCA mechanism can improve the COVID-19 segmentation performance.

A patient with end-stage renal disease who recovered from coronavirus disease 2019 then received a kidney transplant.

Since its emergence in December 2019 many end-stage renal disease (ESRD) patients have been infected with coronavirus disease 2019 (COVID-19). Herein, we describe the case of an ESRD patient who received a kidney transplant after recovering from COVID-19. We described the clinical course of COVID-19 and kidney transplant management, including the patient's symptoms, laboratory results, computed tomography, and antibody profiles. He recovered well, without complications. Chest computed tomography, PCR, and IgG results indicated no recurrence of COVID-19 during the subsequent two weeks. Therefore, kidney transplantation is feasible in an ESRD patient who has recovered from COVID-19, under a normal immunosuppressive regimen.

Retropharyngeal Abscess in an Adult With Pneumonia During COVID-19 Outbreak.

BACKGROUND: Retropharyngeal abscesses are rarely reported in adults and occur mostly in patients with immunocompromised or as a foreign body complication. Admittedly, the treatment of retropharyngeal abscesses frequently involves surgical drainage to achieve the best results. However, when retropharyngeal abscesses occurred in a highly suspected patient with COVID-19, the managements and treatments should be caution to prevent the spread of the virus. CLINICAL PRESENTATION: On February 13, a 40-year-old male with retropharyngeal abscesses turned to our department complaining dyspnea and dysphagia. In addition, his chest CT scan shows a suspected COVID-19 infection, thus making out Multiple Disciplinary Team determine to perform percutaneous drainage and catheterization through left anterior cervical approach under the guidance of B-ultrasound. Finally, the patient recovered and was discharged from the hospital on February 27 after 14 days of isolation. There was no recurrence after half a year follow-up. CONCLUSIONS: By presenting this case, we aim at raising awareness of different surgical drainage methods and summarizing our experience in the management of retropharyngeal abscesses during the outbreak of COVID-19.

The application of Temporary Ark Hospitals in controlling COVID-19 spread: The experiences of one Temporary Ark Hospital, Wuhan, China.

Coronavirus disease 2019 (COVID-19) had its evolution in Wuhan, Hubei Province, China, and now it has spread around the world, resulting in a large number of deaths. Temporary Ark hospitals (TAHs) have played an important role in controlling the spread of the epidemic in the city of Wuhan. Taking one TAH with 800 beds as an example, we summarized details of the layout, setting, working mode of medical staff, patient management, admission standards, discharge standards, and standards for transferring to another hospital, hospital operation, and so on. Over the period of operation, a total of 1124 patients were admitted for treatment. Of these, 833 patients were cured and discharged from the hospital and 291 patients were transferred to other designated hospitals, owing to aggravation of their condition. The achievement was to have zero infection for medical staff, zero in-hospital deaths among admitted patients, and zero readmission for discharged patients. The rapid deployment of TAH provided a suitable place for treating mild/moderate or no asymptomatic COVID-19 patients, which successfully helped to control the infection in Wuhan. The successful model of TAH would rapidly and effectively control the spread of COVID-19 in other cities.