MCA-UNet: multi-scale cross co-attentional U-Net for automatic medical image segmentation.

Medical image segmentation is a challenging task due to the high variation in shape, size and position of infections or lesions in medical images. It is necessary to construct multi-scale representations to capture image contents from different scales. However, it is still challenging for U-Net with a simple skip connection to model the global multi-scale context. To overcome it, we proposed a dense skip-connection with cross co-attention in U-Net to solve the semantic gaps for an accurate automatic medical image segmentation. We name our method MCA-UNet, which enjoys two benefits: (1) it has a strong ability to model the multi-scale features, and (2) it jointly explores the spatial and channel attentions. The experimental results on the COVID-19 and IDRiD datasets suggest that our MCA-UNet produces more precise segmentation performance for the consolidation, ground-glass opacity (GGO), microaneurysms (MA) and hard exudates (EX). The source code of this work will be released via https://github.com/McGregorWwww/MCA-UNet/.

Affordable, portable and self-administrable electrical impedance tomography enables global and regional lung function assessment.

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases. It also requires challenging breathing maneuvers difficult for elderlies, children, and diseased patients. Here, we actualized an affordable, portable, and self-administrable electrical impedance tomography (EIT) system for home-based lung function assessment and telemedicine. Through simultaneous EIT-spirometry trials on healthy subjects, we demonstrated that our device can predict spirometry indicators over a wide range and can provide regional mapping of these indicators. We further developed a close-to-effortless breathing paradigm and tested it by longitudinally monitoring a COVID-19 discharged subject and two healthy controls with results suggesting the paradigm can detect initial deterioration followed by recovery. Overall, the EIT system can be widely applicable for lung function screening and monitoring both at homes and clinics.

Mental health among healthcare workers during the prolonged COVID-19 pandemic: A cross-sectional survey in Jilin Province in China

Background The prolonged COVID-19 pandemic has seriously impacted the mental health of healthcare workers. This study aimed to explore the mental health status of healthcare workers, compare the differences in mental health between physicians and nurses, and verify the impact of risk perception on mental health in the long-term COVID-19 pandemic in Jilin Province, China. Methods A stratified random sample was used to conduct an on-site questionnaire survey in December 2020 to measure the mental health status, risk perceptions, and demographic characteristics of healthcare workers in Jilin Province, China. A total of 3,383 participants completed the questionnaire survey, of which 3,373 were valid questionnaires. Results A total of 23.6% (n = 795) of participants had symptoms of depression, 27.4% (n = 923) had symptoms of anxiety, and 16.3% (n = 551) had symptoms of stress. Physicians reported significantly higher rates of depression and anxiety than nurses (p = 0.023, p = 0.013, respectively). There was no significant difference in the proportion of participants with stress between physicians and nurses (p = 0.474). Multivariate logistic regression results showed that healthcare workers who had a high level of risk perception were more likely to have symptoms of depression (AOR = 4.12, p < 0.001), anxiety (AOR = 3.68, p < 0.001), and stress (AOR = 4.45, p < 0.001) after controlling for other variables. Conclusion At least one in six healthcare workers experienced mental health problems, and physicians were more likely than nurses to suffer from depression during the prolonged COVID-19 epidemic. Risk perception was highly predictive of depression, anxiety, and stress symptoms in medical staff. Public health interventions are needed to mitigate the long-term psychological impact of the COVID-19 pandemic.

Work Stress, Health Status and Presenteeism in Relation to Task Performance Among Chinese Medical Staff During COVID-19 Pandemic.

Objectives: This study aims to evaluate the direct effects of work stress, health status and presenteeism on task performance, and further explore the mediating effects of health status and presenteeism, hoping to provide theoretical basis for improving the performance of medical staff. Methods: A cross-sectional study was conducted among medical staff in Jilin Province, Northeast China. The Challenge and Hindrance-Related Self-Reported Stress scale, Short Form-8 Health Survey scale, Stanford Presenteeism Scale and Task Performance Scale were adopted to assess the work stress, health status, presenteeism and task performance of medical staff. Results: A total of 4,347 questionnaires were distributed among medical staff, and 4261 were valid, for an effective rate of 98.02%. The mean scores for work stress, health status, presenteeism and task performance were 2.05 ± 0.84, 4.18 ± 0.68, 2.15 ± 0.79 and 4.49 ± 0.64, respectively. The ANOVA results showed that there were significant differences in the task performance scores between different genders, ages, marital statuses, professional titles, departments and work years (P < 0.05). Work stress (ß = -0.136, P < 0.001) and presenteeism (ß = -0.171, P < 0.001) were negative predictors of task performance. Health status (ß = 0.10; P < 0.001) was positive predictor of task performance. Health status (ß = -0.070; P < -0.001) and presenteeism (ß = -0.064; P < 0.001) mediated the relationship between work stress and task performance (P < 0.001). Presenteeism mediated the relationship between health status and task performance (ß = 0.07; P < 0.001). Conclusion: Work stress and presenteeism had significant negative impact on the task performance of medical staff; health status had a significant positive effect on task performance. Meanwhile, health status and presenteeism played a mediating role in the relationship between work stress and task performance, and presenteeism played a mediating role in the relationship between health status and task performance. Reasonable assignment of tasks can reduce the work stress, but to improve the performance of medical staff, we should pay more attention on improving health, such as making health-related safeguard measures, raising awareness, building a platform, etc.

A comparison of Remdesivir versus gold cluster in COVID-19 animal model: A better therapeutic outcome of gold cluster.

While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo . We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters.

Smart Mushroom-Inspired Imprintable and Lightly Detachable (MILD) Microneedle Patterns for Effective COVID-19 Vaccination and Decentralized Information Storage.

The key to controlling the spread of the coronavirus disease 2019 (COVID-19) and reducing mortality is highly dependent on the safe and effective use of vaccines for the general population. Current COVID-19 vaccination practices (intramuscular injection of solution-based vaccines) are limited by heavy reliance on medical professionals, poor compliance, and laborious vaccination recording procedures, resulting in a waste of health resources and low vaccination coverage, etc. In this study, we developed a smart mushroom-inspired imprintable and lightly detachable (MILD) microneedle platform for the effective and convenient delivery of multidose COVID-19 vaccines and decentralized vaccine information storage. The mushroom-like structure allows the MILD system to be easily pressed into the skin and detached from the patch base, acting as a "tattoo" to record the vaccine counts in situ without any storage equipment, offering quick accessibility and effortless readout, saving a great deal of valuable time and energy for both patients and health professionals. After loading inactivated SARS-CoV-2 virus-based vaccines, MILD system induced a high level of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) in vivo without eliciting systemic toxicity and local damage. Collectively, this smart delivery platform serves as a promising carrier to improve COVID-19 vaccination efficacy through its dual capabilities of vaccine delivery and in situ data storage, thus exhibiting great potential for helping to contain the COVID-19 pandemic or a resurgence.

A comparison of Remdesivir versus gold cluster in COVID-19 animal model: a better therapeutic outcome of gold cluster

While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo. We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters. Graphical

Sustained Delivery of SARS-CoV-2 RBD Subunit Vaccine Using a High Affinity Injectable Hydrogel Scaffold.

The receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein that mediates viral entry into host cells is a good candidate immunogen for vaccine development against coronavirus disease 2019 (COVID-19). Because of its small size, most preclinical and early clinical efforts have focused on multimerizing RBD on various formats of nanoparticles to increase its immunogenicity. Using an easily administered injectable hydrogel scaffold that is rationally designed for enhanced retainment of RBD, an alternative and facile approach for boosting RBD immunogenicity in mice is demonstrated. Prolonged delivery of poly (I:C) adjuvanted RBD by the hydrogel scaffold results in sustained exposure to lymphoid tissues, which elicits serum IgG titers comparable to those induced by three bolus injections, but more long-lasting and polarized toward TH 1-mediated IgG2b. The hydrogel scaffold induces potent germinal center (GC) reactions, correlating with RBD-specific antibody generation and robust type 1 T cell responses. Besides being an enduring RBD reservoir, the hydrogel scaffold becomes a local inflammatory niche for innate immune cell activation. Collectively, the injectable hydrogel scaffold provides a simple, practical, and inexpensive means to enhance the efficacy of RBD-based subunit vaccines against COVID-19 and may be applicable to other circulating and emerging pathogens.

Cinobufacini Improves the Respiratory Function of Severe COVID-19 Patients

Targeted therapeutics for SARS-CoV-2 virus caused COVID-19 are in urgent need. Cinobufacini has been reported to have broad-spectrum antiviral effects and widely used in Southeast Asian countries. This study aims to assess the efficacy of Cinobufacini injection in treating patients with severe COVID-19. A randomized preliminary clinical trial was conducted and eligible patients were allocated to receive general treatment plus Cinobufacini injection or only general treatment as control for 7 days. The primary outcomes of the oxygenation index PaO2/FiO2 and ROX, secondary outcomes of white blood cell count, respiratory support step-down time (RSST), safety indicators, etc were monitored. After 7 days of treatment, the oxygenation index was improved in 95.2% patients in the treatment group compared with 68.4% in the control group. The PaO2/FiO2 and ROX indices in the treatment group (mean, 226.27±67.35 and 14.01±3.99 respectively) were significantly higher than the control group (mean, 143.23±51.29 and 9.64±5.54 respectively). The RSST was 1 day shorter in the treatment group. Multivariate regression analysis suggested that Cinobufacini injection contributed the most to the outcome of PaO2/FiO2. No obvious adverse effects were observed. The preliminary data showed that Cinobufacini injection had apparent efficacy in improving the respiratory function of patients with severe COVID-19.

MSDS-UNet: A multi-scale deeply supervised 3D U-Net for automatic segmentation of lung tumor in CT.

Lung cancer is one of the most common and deadly malignant cancers. Accurate lung tumor segmentation from CT is therefore very important for correct diagnosis and treatment planning. The automated lung tumor segmentation is challenging due to the high variance in appearance and shape of the targeting tumors. To overcome the challenge, we present an effective 3D U-Net equipped with ResNet architecture and a two-pathway deep supervision mechanism to increase the network's capacity for learning richer representations of lung tumors from global and local perspectives. Extensive experiments on two real medical datasets: the lung CT dataset from Liaoning Cancer Hospital in China with 220 cases and the public dataset of TCIA with 422 cases. Our experiments demonstrate that our model achieves an average dice score (0.675), sensitivity (0.731) and F1-score (0.682) on the dataset from Liaoning Cancer Hospital, and an average dice score (0.691), sensitivity (0.746) and F1-score (0.724) on the TCIA dataset, respectively. The results demonstrate that the proposed 3D MSDS-UNet outperforms the state-of-the-art segmentation models for segmenting all scales of tumors, especially for small tumors. Moreover, we evaluated our proposed MSDS-UNet on another challenging volumetric medical image segmentation task: COVID-19 lung infection segmentation, which shows consistent improvement in the segmentation performance.

Rational optimization of a human neutralizing antibody of SARS-CoV-2.

SARS-CoV-2 has caused a worldwide epidemic of coronavirus disease 19 (COVID-19). Antibody drugs present an effective weapon for tens of millions of COVID-19 patients. Antibodies disrupting the interactions between the receptor-binding domain (RBD) of SARS-CoV-2 S protein and the angiotensin converting enzyme 2 (ACE2) effectively block SARS-CoV-2 cell entry into host cells. In order to rapidly develop more potent neutralizing antibodies, we utilized virtual scanning mutageneses and molecular dynamics simulations to optimize the antibody of P2B-2F6 isolated from single B cells of SARS-CoV-2 infected patients. Two potent P2B-2F6 mutants, namely H:V106R and H:V106R/H:P107Y, were found to possess higher binding affinities with the RBD domain of SARS-CoV-2 than others. Polar interactions are preferred near 106 and 107 paratope residues of the heavy chain. The mutations also increase the hydrogen-bonding network formed between the antibody and the RBD. Notably, the optimized antibodies possess potential neutralizing activity against the alarming SARS-CoV-2 variant of N501Y. This study provides insights into structure-based optimization of antibodies with higher affinity to the antigen. We hope that our proposed antibody mutants could contribute to the development of improved therapies against COVID-19.

One-Year and Consequences of COVID-19 in Cancer Patients: a Cohort Study (preprint)

Background The study aim was to investigate one-year all-cause mortality and health consequences of cancer COVID-19 patients in China, stratified by primary tumor subtype.Methods In this multicenter cohort study, 166 cancer COVID-19 patients were studied along with 498 gender- and age-matched non-cancer COVID-19 patients in four hospitals in Wuhan, China, admitted 2020/01/01-2020/03/18, as well as with 498 parallel gender-, age-, and cancer subtype- matched non-COVID cancer patients hospitalized between 2019/01/01-2020/03/17. All patients were followed-up with a telephone survey to assess health consequences. Cox proportional hazards regression were used for risk analysis.Results In the three cohorts of median age of 65 ± 1 year and 49% male, the one-year all-cause mortality and hospital mortality rates of Cancer COVID-19 Cohort, 30% and 20% respectively, were significantly higher than COVID-19 Cohort (9% and 8%), and Cancer Cohort (16% and 2%). The 12-month all-cause post-discharge mortality rate of Cancer COVID-19 Cohort (11%) was higher than COVID-19 Cohort (0.4%), but similar to Cancer Cohort (15%). The high 1-year all-cause mortality was among hematologic malignancies (65%) and then nasopharyngeal, brain and skin tumors (45%), digestive system (43%), and lung (32%). the rate was low among genitourinary (14%), female genital (13%), breast (11%), and thyroid (0). As for patients having at least one symptom at the 1-year follow-up, Cancer COVID-19 Cohort (23%, 26/114) is similar to COVID-19 Cohort (30%, 130/432).Discussion Cancer COVID-19 patients showed a high rate of hospitalization mortality, but not after discharged, signifying the strong acute adverse effect of COVID-19 on cancer patients while little was in long-term effect. Risk stratification showed that hematologic malignancies, nasopharyngeal, brain, digestive system and lung tumors were high risk, while genitourinary, female genital, breast and thyroid were low risk which was similar to non-cancer COVID-19.Conclusions COVID-19 had little effect of 1-year mortality and sequelae for cancer survivors discharged from SARS-CoV-2 virus infection. Different tumor subtypes had different effect of COVID-19. COVID-19 patients with thyroid, breast, female genital, genitourinary tumor had low risk mortality which was similar to non-cancer patients.

Elevated serum ferritin level effectively discriminates severity illness and liver injury of coronavirus disease 2019 pneumonia.

AIM: Ferritin is a hepatic protein that plays vital roles in diagnosing and predicting diseases, but its potential in coronavirus disease 2019 (COVID-19) remains unknown. METHOD: We collected clinical records from 79 COVID-19 patients at Wuhan Union hospital (China). Spearman's correlation analysis, receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves were employed. RESULTS: Patients with elevated ferritin levels had a higher incidence of severity illness (50.0 vs 2.9%) and liver injury (52.3 vs 20.0%) when compared with patients with normal ferritin levels (p < 0.05). Ferritin could effectively identify the severity of illness (ROC area 0.873) and liver injury (ROC area 0.752). The elevated ferritin group showed longer viral clearance time (median 16 vs 6 days, p < 0.001) and in-hospital length (median 18 vs 10 days, p < 0.001). CONCLUSIONS: It suggests that ferritin could act as an easy-to-use tool to identify liver injury and severity illness and predict the prognosis of COVID-19 patients. Intensive surveillance is necessary for patients with abnormal ferritin levels.

Novel coronavirus pneumonia (COVID-19) after pulmonary surgery: A case report / 中国胸心血管外科临床杂志

@#There was a male novel coronavirus (2019-nCoV, SARS-CoV-2) pneumonia (COVID-19) patient after pulmonary surgery at age of 61 years. The patient had no clear history of contact COVID-19 patient before surgery. He developed transient fever on the 4th day after surgery. The body temperature returned to normal on the 5th day after antibiotic adjustment. The patient developed fever and fatigue again on the 6th day after surgery. A chest CT scan revealed postoperative pneumonia. The patient was treated by ganciclovir and moxifloxacin hydrochloride. The patient's temperature gradually decreased on the 7th to 9th days after the operation. CT scan on the 10th day after surgery showed viral pneumonia, so we immediately raised the level of protection. The novel coronavirus nucleic acid test was positive. The patient was immediately transferred to the designated hospital for treatment. The patient was treated by arbidol, moxifloxacin, human immunoglobulin (PH4), ambroxol and other nutritional symptomatic and supportive treatment. The patient's condition is currently stable. Ten people in close contact with the patient developed symptoms, and their CT scans showed viral pneumonia. Six of them were positive in nucleic acid tests, and the others were still under quarantine observation. This shows that it is easy to confuse the imaging manifestations of pneumonia with novel coronavirus pneumonia after lung surgery. We should perform nucleic acid detection as soon as possible in the early diagnosis of CT and reformulate the treatment protocol.

A case report with COVID-19 during perioperative period of lobectomy.

RATIONALE: Currently, COVID-19 has made a significant impact on many countries in the world. However, there have been no reported cases of pulmonary lobectomy with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection. We are the first to report such a case. PATIENT CONCERNS: We report a 63-year-old Wuhan male patient with smoking history of 40 cigarettes per day for 40 years. He sought medical consultation for right lower lung nodules found by CT scan. DIAGNOSES AND INTERVENTIONS: The patient's postoperative pathological diagnosis was squamous cell carcinoma of the right lower lung. On the fourth day after the operation, the real-time reverse transcription polymerase chain reaction test showed a positive result. After the operation, we routinely give symptomatic treatments such as anti-infection, nebulization and oxygen inhalation. We also change antibiotics several times depending on the patient's condition. OUTCOMES: The patient's condition continued to deteriorate. On the fifth day after surgery, the patient died despite medical treatment. LESSONS: We are the first to report the diagnosis and treatment process of patients with COVID-19 during perioperative period of lobectomy. It provides a case for the postoperative management of such patients.

The important role of polysaccharides from a traditional Chinese medicine-Lung Cleansing and Detoxifying Decoction against the COVID-19 pandemic.

The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application.