Experience of parents in delivering pediatric tuina to children with symptoms of attention deficit hyperactivity disorder during the COVID-19 pandemic: qualitative findings from focus group interviews.

BACKGROUND: Evidence suggests that pediatric tuina, a modality of traditional Chinese medicine (TCM), might have beneficial effects on the symptoms of attention deficit hyperactivity disorder (ADHD), such as overall improvements in concentration, flexibility, mood, sleep quality, and social functioning. This study was conducted to understand the facilitators and barriers in the delivery of pediatric tuina by parents to children with ADHD symptoms. METHODS: This is a focus group interview embedded in a pilot randomized controlled trial on parent-administered pediatric tuina for ADHD in preschool children. Purposive sampling was employed to invite 15 parents who attended our pediatric tuina training program to participate voluntarily in three focus group interviews. The interviews were audio-recorded and transcribed verbatim. The data were analyzed through template analysis. RESULTS: Two themes were identified: (1) facilitators of intervention implementation and (2) barriers to intervention implementation. The theme of the facilitators of intervention implementation included the subthemes of (a) perceived benefits to children and parents, (b) acceptability to children and parents, (c) professional support, and (d) parental expectations of the long-term effects of the intervention. The theme of barriers to intervention implementation included the subthemes of (a) limited benefits for children's inattention symptoms, (b) manipulation management difficulties, and (c) limitations of TCM pattern identification. CONCLUSION: Perceived beneficial effects on the children's sleep quality and appetite and parent-child relationships, as well as timely and professional support, mainly facilitated the implementation of parent-administered pediatric tuina. Slow improvements in the children's inattention symptoms and the possible inaccuracies of online diagnosis were the dominant barriers of the intervention. Parents have high expectations for the provision of long-term professional support during their practice of pediatric tuina. The intervention presented here can be feasibly used by parents.

Research progress on distribution and exposure risk of microbial aerosols in animal houses

Environmental aerosols in animal houses are closely related to the productive performance and health level of animals living in the houses. Preferable housing environments can improve animal welfare and production efficiency, so it is necessary to monitor and study these environments. In recent years, there have been many large-scale outbreaks of respiratory diseases related to biological aerosols, especially the novel coronavirus that has been sweeping the world. This has attracted much attention to the mode of aerosol transmission. With the rapid development of large-scale and intensive breeding, microbial aerosols have gradually become the main factor of environmental pollution in animal houses. They not only lead to a large-scale outbreak of infectious diseases, but they also have a certain impact on the health of animals and employees in the houses and increase the difficulty of prevention and control of animal-borne diseases. This paper reviews the distribution, harm, and control measures of microbial aerosols in animal house environments in order to improve people's understanding of them.

Coronavirus Disease Pandemic Effect on Medical-Seeking Behaviors Even in One Resource-Competent Community: A Case Controlled Study.

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic had overwhelming impacts on medical services. During its initial surge, Taiwan was unique in maintaining its medical services without imposing travel restrictions, which provided an ideal environment in which to test if the fear of becoming infected with COVID-19 interfered with health-seeking behavior (HSB). We tested this hypothesis among adults with acute complicated appendicitis (ACA). (2) Methods: Adults with acute appendicitis were enrolled between 1 January and 30 June 2020 (COVID-19 period). The first two quarters of the preceding 3 years were defined as a historical control group. Outcome measures included the rate of ACA and the number of hospital stays. (3) Results: The COVID-19 era included 145 patients with acute appendicitis. Compared to the historical control (320 patients), the COVID-19 era was significantly associated with a higher length of symptom duration until presentation to the emergency room within >48 h (17.2% vs. 9.1%, p = 0.011), a higher incidence of ACA (29.7% vs. 19.4%, p = 0.014), and a longer length of hospital stays (5.0 days vs. 4.0 days, p = 0.043). The adjusted models showed that the COVID-19 period had a significant relationship with a higher rate of ACA (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.23-2.52; p = 0.008) and longer length of hospital stays (OR= 2.10; 95% CI: 0.92 to 3.31; p < 0.001). (4) Conclusions: The fear of COVID-19 may prohibit patients from seeking medical help, worsening their clinical outcomes. The surgical community should take action to provide scientific information to relive mental stress.

How to build a novel burst disease diagnostics for hunting potential infection source: the enlightenment from screening patients via combining viral and antibody testing at the COVID-19 pandemic early stage (preprint)

Purpose: We aimed to summarize the diagnostic strategies used to identify potential patients with COVID-19 among inbound overseas travelers in Xiamen, China.Methods: From October 2020 to December 2020, 180,000 inbound overseas travelers were subjected to government quarantine in Xiamen, China. We evaluated the screening efficiency of combining viral and antibody testing strategies to identify potential patients with COVID-19. Results: The COVID-19 positive rate was 0.17% (306/180,000). There was no difference between the combined PCR and antibody and the PCR testing strategy for screening COVID-19(2.0 [IQR,2.0–3.0] vs. 2.0[IQR,2.0–2.0]; P= 0.175). The results for the combined screening strategy were available 4 days earlier than those for the PCR testing strategy (3.0 [IQR, 3.0–3.0] vs. 7.0[IQR, 7.0–14.0], P=0.000). Compared with the non-key screening population, the key screening population showed less PCR rounds (2.0 [IQR, 2.0–2.0] vs. 2.0[IQR, 2.0–3.0]; (P=0.008) and time (3.0[IQR, 3.0–3.0] vs. 7.0[IQR, 7.0–14.0]; P=0.000) for screening COVID-19. Conclusion: Combining viral and antibody testing strategies is effective; it allows timely identification of the source of COVID-19 infection. Moreover, this strategy can be used for close contacts or sub-close contacts of patients with COVID-19 to reduce the risk of SARS-CoV-2 transmission.

A phase II study of N-acetylcysteine in cancer patients with severe COVID-19: clinical outcomes and biological correlates (preprint)

Acute SARS-CoV-2 infection results in high mortality rates in patients with cancer with patients dying from a combination of virus and inflammation-driven respiratory failure. We conducted a two-arm, single-institution phase II study of N-acetylcysteine in patients admitted to Memorial Sloan Kettering Cancer Center with severe COVID-19 from May 2020 to April 2021. A total of 42 patients were treated: 13 patients in arm A (ICU) and 29 patients in arm B (non-ICU). In total, 23% of patients in arm A and 69% of patients in arm B met the predetermined clinical definition of treatment success. Patients meeting a successful primary endpoint were more likely to exhibit decreases in systemic levels of interleukin-6 and C-reactive protein and had both higher proportions of PD-1-expressing effector memory and fewer terminally differentiated CD8+ T-cells. These results suggest that many patients with cancer and severe COVID-19 experience clinical and immunologic improvement with N-acetylcysteine therapy.

Modulating the Fluorescence of Silver Nanoclusters Wrapped in DNA Hairpin Loops via Confined Strand Displacement and Transient Concatenate Ligation for Amplifiable Biosensing.

It is intriguing to modulate the fluorescence emission of DNA-scaffolded silver nanoclusters (AgNCs) via confined strand displacement and transient concatenate ligation for amplifiable biosensing of a DNA segment related to SARS-CoV-2 (s2DNA). Herein, three stem-loop structural hairpins for signaling, recognizing, and assisting are designed to assemble a variant three-way DNA device (3WDD) with the aid of two linkers, in which orange-emitting AgNC (oAgNC) is stably clustered and populated in the closed loop of a hairpin reporter. The presence of s2DNA initiates the toehold-mediated strand displacement that is confined in this 3WDD for repeatable recycling amplification, outputting numerous hybrid DNA-duplex conformers that are implemented for a transient "head-tail-head" tandem ligation one by one. As a result, the oAgNC-hosted hairpin loops are quickly opened in loose coil motifs, bringing a significant fluorescence decay of multiple clusters dependent on s2DNA. Demonstrations and understanding of the tunable spectral performance of a hairpin loop-wrapped AgNC via switching 3WDD conformation would be highly beneficial to open a new avenue for applicable biosensing, bioanalysis, or clinical diagnostics.

Experiences of Older Adults with Frailty Not Completing an Advance Directive: A Qualitative Study of ACP Conversations

Advance care planning (ACP) facilitates individuals to proactively make decisions on their end-of-life care when they are mentally competent. It is highly relevant to older adults with frailty because they are more vulnerable to cognitive impairment, disabilities, and death. Despite devoting effort to promoting ACP among them, ACP and advance directive completion rates remain low. This study aims to explore the experiences among frail older adults who did not complete an advance directive after an ACP conversation. We conducted a thematic analysis of audiotaped nurse-facilitated ACP conversations with frail older adults and their family members. We purposively selected ACP conversations from 22 frail older adults in the intervention group from a randomized controlled trial in Hong Kong who had ACP conversation with a nurse, but did not complete an advance directive upon completing the intervention. Three themes were identified: “Refraining from discussing end-of-life care”, “Remaining in the here and now”, and “Relinquishing responsibility over end-of-life care decision-making”. Participation in ACP conversations among frail older adults and their family members might improve if current care plans are integrated so as to increase patients’ motivation and support are provided to family members in their role as surrogate decision-makers.

Broadly neutralizing antibodies target the coronavirus fusion peptide (preprint)

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.

Venous Thromboembolism in COVID-19 Patients and Prediction Model: A Multicenter Cohort Study (preprint)

Background: Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses in COVID-19 patients are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in prevention, early identification and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients. Methods: This is a multicenter, retrospective database of four main health systems in southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models including random forest, multiple logistic regression, multiple linear regression, and decision trees were built on the primary outcome of in-hospital acute deep vein thrombosis and pulmonary embolism and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using area under the receiver operating characteristic curve and confusion matrix. Results: The cohort included 3531 admissions, 3526 had discharge diagnosis, and 6.68% patients developed acute VTE (N=236). VTE group had a longer hospital and ICU LOS than non-VTE group (hospital LOS 12.2 days vs 8.8 days, p<0.001; ICU LOS 3.8 days vs 1.9 days, p<0.001). 9.8% patients in VTE group required more advanced oxygen support, compared to 2.7% patients in non-VTE group (p<0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes and inflammatory markers were predictors of in-hospital VTE in COVID-19 patients. Conclusions: and Relevance Patients with COVID-19 have increased risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making clinical judgment on empirical dosages of anticoagulation.

Design of SARS-CoV-2 Mpro, PLpro dual-target inhibitors based on deep reinforcement learning and virtual screening.

Background: Since December 2019, SARS-CoV-2 has continued to spread rapidly around the world. The effective drugs may provide a long-term strategy to combat this virus. The main protease (Mpro) and papain-like protease (PLpro) are two important targets for the inhibition of SARS-CoV-2 virus replication and proliferation. Materials & methods: In this study, deep reinforcement learning, covalent docking and molecular dynamics simulations were used to identify novel compounds that have the potential to inhibit both Mpro and PLpro. Results & conclusion: Three compounds were identified that can effectively occupy the Mpro protein cavity with the PLpro protein cavity and form high-frequency contacts with key amino acid residues (Mpro: His41, Cys145, Glu166; PLpro: Cys111). These three compounds can be further investigated as potential lead compounds for SARS-CoV-2 inhibitors.

Antibiotic Therapy in the Treatment of COVID-19 Pneumonia: Who and When?

BACKGROUND: COVID-19 imposes challenges in antibiotic decision-making due to similarities between bacterial pneumonia and moderate to severe COVID-19. We evaluated the effects of antibiotic therapy on the clinical outcomes of COVID-19 pneumonia patients and diagnostic accuracy of key inflammatory markers to inform antibiotic decision-making. METHODS: An observational cohort study was conducted in patients hospitalised with COVID-19 at the National Centre for Infectious Diseases and Tan Tock Seng Hospital, Singapore, from January to April 2020. Patients were defined as receiving empiric antibiotic treatment for COVID-19 if started within 3 days of diagnosis. RESULTS: Of 717 patients included, 86 (12.0%) were treated with antibiotics and 26 (3.6%) had documented bacterial infections. Among 278 patients with COVID-19 pneumonia, those treated with antibiotics had more diarrhoea (26, 34.7% vs. 24, 11.8%, p < 0.01), while subsequent admissions to the intensive care unit were not lower (6, 8.0% vs. 10, 4.9% p = 0.384). Antibiotic treatment was not independently associated with lower 30-day (adjusted odds ratio, aOR 19.528, 95% confidence interval, CI 1.039-367.021) or in-hospital mortality (aOR 3.870, 95% CI 0.433-34.625) rates after adjusting for age, co-morbidities and severity of COVID-19 illness. Compared to white cell count and procalcitonin level, the C-reactive protein level had the best diagnostic accuracy for documented bacterial infections (area under the curve, AUC of 0.822). However, the sensitivity and specificity were less than 90%. CONCLUSION: Empiric antibiotic use in those presenting with COVID-19 pneumonia did not prevent deterioration or mortality. More studies are needed to evaluate strategies to diagnose bacterial co-infections in these patients.

Automatic CT Whole-Lung Segmentation in Radiomics Discrimination: Methodology and Application in Pneumonia Diagnosis and Distinguishment

Radiomics based on lesion segmentation has been widely accepted for disease diagnosis;however, it is difficult to precisely determine the boundary for pneumonia due to its diffuse characteristics. In this study, we aimed to propose an automatic radiomics method using whole-lung segmentation in pneumonia discrimination and assist clinical practitioners in fast and accurate diagnosis. In the discovery set, data from 151 participants diagnosed with type A or B influenza virus pneumonia, 63 diagnosed with coronavirus disease 2019 (COVID-19) and 50 healthy participants were collected. The three groups of data were compared in pairs. A total of 117 radiomics features were extracted from whole-lung images segmented by a four-layer U-net. We then utilized a logistic regression model to train the model and used the area under the receiver operating characteristic curve (AUC) to assess its performance. The L1 regularization term was used in feature selection, and 10-fold cross-validation was used to tune the hyperparameters. Fourteen radiomics features were selected to classify influenza pneumonia and health, and the AUC was 0.957 (95% confidential interval (CI): 0.939, 0.976) in the training set and 0.914 (95% CI: 0.866, 0.963) in the testing set. Eighteen features were selected for COVID-19 and health, and the AUC was 0.949 (95% CI: 0.926, 0.973)in the training set and 0.911 (95% CI: 0.859, 0.963) in the testing set. Twenty-eight features were selected for influenza virus pneumonia and COVID-19, and the AUC was 0.895 (95% CI: 0.870, 0.920) in the training set and 0.839 (95% CI: 0.791, 0.887) in the testing set. The results show that the automatic radiomics model based on whole lung segmentation is effective in distinguishing influenza virus pneumonia, COVID-19 and health, and may assist in the diagnosis of influenza virus pneumonia and COVID-19.

Decomposition approach for Stackelberg P-median problem with user preferences (preprint)

The P-median facility location problem with user preferences (PUP) studies an operator that locates P facilities to serve customers/users in a cost-efficient manner, upon anticipating customer preferences and choices. The problem can be visualized as a leader-follower game in which the operator is the leader that opens facilities, whereas the customer is the follower who observes the operator's location decision at first and then seeks services from the most preferred facility. Such a modeling perspective is of practical importance as we have witnessed its applications to various problems, such as the establishment of power plants in energy markets and the location of healthcare service centers for COVID-19 Vaccination. Despite that a considerable number of solution methodologies have been proposed, many of them are heuristic methods whose solution quality cannot be easily verified. Moreover, due to the hardness of the problems, existing exact approaches have limited performance. Motivated by these observations, we aim to develop an efficient exact algorithm for solving large-scale PUP models. We first propose a branch-and-cut decomposition algorithm and then design accelerated techniques to further enhance the performance. Using a broad testbed, we show that our algorithm outperforms various exact approaches by a large margin, and the advantage can go up to several orders of magnitude in terms of computational time in some datasets. Finally, we conduct sensitivity analysis to draw additional implications and to highlight the importance of considering user preferences when they exist.

Surviving Work from Home: Observations from Singapore.

Circuit Breaker measures were implemented in Singapore on 7 April 2020, and work from home arrangements were officially made compulsory for most due to COVID-19. This study assessed the effects of prolonged telecommuting within the Singapore Police. Items on productivity, satisfaction with telecommuting, work-life effectiveness, feelings of safety, stress levels, connectedness to and support by colleagues, and supervisors were included. The study found that while prolonged telecommuting did not have any impact on levels of satisfaction with telecommuting, individuals with caregiving duties were significantly less satisfied with telecommuting than non-caregivers. Implications of the findings were discussed with respect to the necessary support required by officers while telecommuting. Recommendations on how individuals can practice self-care while telecommuting for prolonged periods were also proposed.

Feasibility and utility of facemask sampling in the detection of SARS-CoV-2 during an ongoing pandemic.

Easy access to screening for timely identification and isolation of infectious COVID-19 patients remains crucial in sustaining the international efforts to control COVID-19 spread. A major barrier limiting broad-based screening is the lack of a simple, rapid, and cost-effective COVID-19 testing method. We evaluated the feasibility and utility of facemask sampling in a cohort of 42 COVID-19-positive and 36 COVID-19-negative patients. We used a prototype of Steri-Strips™ (3 M) applied to the inner surface of looped surgical facemasks (Assure), which was worn by patients for a minimum wear time of 3 h, then removed and sent for SARS-CoV-2 PCR testing. Baseline demographics and symptomatology were also collected. Facemask sampling positivity was highest within the first 5 days of symptomatic presentation. Patients with nasopharyngeal and/or oropharyngeal swab SARS-CoV-2 PCR Ct values < 25.09 had SARS-CoV-2 detected on facemask sampling, while patients with Ct values ≥ 25.2 had no SARS-CoV-2 detected on facemask sampling. Facemask sampling can identify patients with COVID-19 during the early symptomatic phase or those with high viral loads, hence allowing timely identification and isolation of those with the highest transmission risk. Given the widespread use of facemasks, this method can potentially be easily applied to achieve broad-based, or even continuous, population screening.

Development of low-cost serological immunoassay to detect antiviral antibodies to Sars-Cov-2 Spike protein (preprint)

Seroconversion to Sars-cov-2 has been widely studied to evaluate infection spreading for epidemiological purpose, or even in studies of protective immunity in convalescent or vaccinated individuals. The viral particle has an envelope harboring the SPIKE glycoprotein, which can be used as an antigen for assay development, to detect antiviral antibodies to Sars-CoV-2. Since several vaccines encode a SPIKE subunit, the full length spike-based immunoassay should be a universal tool to evaluate seroconversion. In this manuscript, we propose a low-cost assay that can be used to detect antiviral IgG to Sars-Cov-2 in human serum.

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients.

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.