In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

Online learning resource recommendation method based on multi-similarity metric optimization under the COVID-19 epidemic.

With the continuous COVID-19 pneumonia epidemic, online learning has become a normal choice for many learners. However, the problems of information overload and knowledge maze have been aggravated in the process of online learning. A learning resource recommendation method based on multi similarity measure optimization is proposed in this paper. We optimize the user score similarity by introducing information entropy, and use particle swarm optimization algorithm to determine the comprehensive similarity weight, and determine the nearest neighbor user with both score similarity and interest similarity through secondary screening in this method. The ultimate goal is to improve the accuracy of recommendation results, and help learners learn more effectively. We conduct experiments on public data sets. The experimental results show that the algorithm in this paper can significantly improve the recommendation accuracy on the basis of maintaining a stable recommendation coverage.

Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects.

SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects (syncytium formation). We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced syncytium-forming ability. Notably, the D614G change found in globally predominant SARS-CoV-2 strains increased infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, these two features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both host proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.IMPORTANCE The development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, a process that contributes to the destruction of the virus-infected cell.

The COVIDTW study: Clinical predictors of COVID-19 mortality and a novel AI prognostic model using chest X-ray.

BACKGROUND: There is a lack of published research on the impact of the first wave of the COVID-19 pandemic in Taiwan. We investigated the mortality risk factors among critically ill patients with COVID-19 in Taiwan during the initial wave. Furthermore, we aim to develop a novel AI mortality prediction model using chest X-ray (CXR) alone. METHOD: We retrospectively reviewed the medical records of patients with COVID-19 at Taipei Tzu Chi Hospital from May 15 to July 15 2021. We enrolled adult patients who received invasive mechanical ventilation. The CXR images of each enrolled patient were divided into 4 categories (1st, pre-ETT, ETT, and WORST). To establish a prediction model, we used the MobilenetV3-Small model with "Imagenet" pretrained weights, followed by high Dropout regularization layers. We trained the model with these data with Five-Fold Cross-Validation to evaluate model performance. RESULT: A total of 64 patients were enrolled. The overall mortality rate was 45%. The median time from symptom onset to intubation was 8 days. Vasopressor use and a higher BRIXIA score on the WORST CXR were associated with an increased risk of mortality. The areas under the curve of the 1st, pre-ETT, ETT, and WORST CXRs by the AI model were 0.87, 0.92, 0.96, and 0.93 respectively. CONCLUSION: The mortality rate of COVID-19 patients who receive invasive mechanical ventilation was high. Septic shock and high BRIXIA score were clinical predictors of mortality. The novel AI mortality prediction model using CXR alone exhibited a high performance.

Highly pathogenic coronaviruses and the kidney.

Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pneumonia epidemic, posing a significant public health challenge in 236 countries, territories, and regions worldwide. Clinically, in addition to the symptoms of pulmonary infection, many patients with SARS-CoV-2 infections, especially those with a critical illness, eventually develop multiple organ failure in which damage to the kidney function is common, ultimately leading to severe consequences such as increased mortality and morbidity. To date, three coronaviruses have set off major global public health security incidents: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2. Among the diseases caused by the coronaviruses, the coronavirus disease 2019 (COVID-19) has been the most impactful and harmful. Similar to with SARS-CoV-2 infections, previous studies have shown that kidney injury is also common and prominent in patients with the two other highly pathogenic coronaviruses. Therefore, in this review, we aimed to comprehensively summarize the epidemiological and clinical characteristics of these three pandemic-level infections, provide a deep analysis of the potential mechanism of COVID-19 in various types of kidney diseases, and explore the causes of secondary kidney diseases of SARS-CoV-2, so as to provide a reference for further research and the clinical prevention of kidney damage caused by coronaviruses.

Interactive training versus self-driven training in the prediction of colorectal polyp histology by trainees using the NICE classification.

BACKGROUND: The COVID-19 pandemic has impacted endoscopic training of the Narrow Band Imaging International Colorectal Endoscopic (NICE) classification, which could accurately predict pathology of colorectal polyps. This study aimed to evaluate the diagnostic performance by trainees of self-driven training vs. interactive training in the prediction of colorectal polyp histology. METHODS: This was a prospective randomized controlled study at five academic centers from January 1, 2021 to May 31, 2021. Trainees with no previous formal training of narrow band imaging or blue light imaging for prediction of colorectal polyp histology were randomly allocated to the self-driven training group or interactive training group. Before and after the training, all trainees were given 20 selected cases of colorectal polyp for testing. Their diagnostic performance was analyzed. RESULTS: Overall, the two training groups showed similar accuracy of NICE classification (79.3% vs. 78.1%; P = 0.637), vessel analysis (77.8% vs. 77.6%, P = 0.939), and surface pattern analysis (78.1% vs. 76.9%, P = 0.616). The accuracy of color analysis in the interactive training group was better (74.4% vs. 80.0%, P = 0.027). For high-confidence predictions, the self-driven training group showed higher accuracy of NICE classification (84.8% vs. 78.7%, P < 0.001) but no difference for analysis of color (79.6% vs. 81.0%), vessel pattern (83.0% vs. 78.5%), and surface pattern (81.8% vs. 78.5%). CONCLUSIONS: Overall, self-driven training showed comparable accuracy of NICE classification, vessel pattern, and surface pattern to interactive training, but lower accuracy of color analysis. This method showed comparable effectiveness and is more applicable than interactive training. It is worth spreading during the COVID-19 pandemic. Trial registration Name of the registry: Chinese Clinical Trial Registry, Trial registration number: ChiCTR2000031659, Date of registration: 06/04/2020, URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=51994.

Prevalence of taste and smell dysfunction in mild and asymptomatic COVID-19 patients during Omicron prevalent period in Shanghai, China: a cross-sectional survey study.

OBJECTIVES: COVID-19, which is caused by SARS-CoV-2, is a severe threat to human health and the economy globally. This study aimed to investigate the prevalence of taste and/or smell dysfunction and associated risk factors in mild and asymptomatic patients with Omicron infection in Shanghai, China.DesignThis was a questionnaire-based cross-sectional study. SETTING: COVID-19 patients at the makeshift hospital in the Shanghai World Expo Exhibition and Convention Centre were recruited from March to April 2022. PARTICIPANTS: In total, 686 COVID-19-infected patients who were defined as mild or asymptomatic cases according to the diagnostic criteria of New Coronavirus Pneumonia Prevention and Control Programme ninth edition (National Health Commission of China, 2022) were enrolled. MEASURES: Data to investigate taste and smell loss and to characterise other symptoms were collected by the modified Chemotherapy-induced Taste Alteration Scale and Sino-Nasal Outcome Test-22 questionnaires. The risk factors for the severity of taste/smell dysfunction were analysed by binary logistic regression models. RESULTS: 379 males (379/686, 55.2%) and 307 females (307/686, 44.8%) completed the questionnaires to record recent changes in taste and smell ability. A total of 302 patients (44%) had chemosensory dysfunction with Omicron infection, of which 22.7% (156/686) suffered from both taste and smell dysfunction. In addition, cough (60.2%), expectoration (40.5%), fever (33.2%) and sore throat (32.5%) were common symptoms during Omicron infection. The quality-of-life-related indicators were negatively associated with participants' self-reported taste and smell dysfunction. CONCLUSIONS: The prevalence of taste or/and smell dysfunction in patients with Omicron infections was 44%. Individuals with chemosensory dysfunction had significantly higher rates of various upper respiratory influenza-like symptoms, xerostomia and bad breath. Moreover, smell dysfunction was a risk factor for the prevalence of taste dysfunction in patients with Omicron infection. TRIAL REGISTRATION NUMBER: ChiCTR 2200059097.

A Heterologous Challenge Rescues the Attenuated Immunogenicity of SARS-CoV-2 Omicron BA.1 Variant in Syrian Hamster Model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

Ocular inflammatory manifestations following COVID-19 vaccinations in Taiwan: A case series.

As a continuing demand for booster shots against SARS-CoV-2, ocular adverse events following the coronavirus disease-2019 (COVID-19) vaccines can cause significant visual impairment, and they warrant a high awareness and detailed documentation of possible ocular inflammatory manifestations. We present a case series of 11 patients presenting with ocular manifestations relevant to vaccine-associated autoimmune response within 6 weeks after the vaccination of the Oxford-AstraZeneca, the Moderna, and Pfizer-BioNTech vaccines at the main tertiary referral center in the most populated and most vaccinated city in Taiwan. Their diagnosis included five acute anterior uveitis, two multiple evanescent white dot syndrome, one probable Vogt-Koyanagi-Harada disease, one anterior scleritis, one relapsed idiopathic panuveitis, and one autoantibody-related central retinal artery occlusion. This report presented a broad spectrum of the ocular inflammatory events following the vaccination of COVID-19. Early recognition of the clinical manifestations mentioned herein with prompt management is crucial in recovering the patients' vision.

Maternal and infant outcomes in women with and without gestational diabetes mellitus in the COVID-19 era in China: Lessons learned

Aims The global COVID-19 pandemic has required a drastic transformation of prenatal care services. Whether the reformulation of the antenatal care systems affects maternal and infant outcomes remains unknown. Particularly, women with gestational diabetes mellitus (GDM) are among those who bear the greatest brunt. Thus, this study aimed to evaluate the impact of COVID-19 lockdown during late pregnancy on maternal and infant outcomes in women stratified by the GDM status in China. Study design The participants were women who experienced the COVID-19 lockdown during late pregnancy (3185 in the 2020 cohort) or not (2540 in the 2019 cohort) that were derived from the Beijing Birth Cohort Study. Maternal metabolic indicators, neonatal outcomes, and infant anthropometrics at 12 months of age were compared between the two cohorts, stratified by the GDM status. Results Participants who experienced COVID-19 lockdown in late pregnancy showed lower gestational weight gain than those in the control cohort. Nevertheless, they displayed a worse metabolic profile. COVID-19 lockdown during pregnancy was associated with higher glycosylated hemoglobin (HbA1c) (β= 0.11, 95% CI = 0.05–0.16, q-value = 0.002) and lower high density lipoprotein cholesterol level (HDL-C) level (β=–0.09, 95% CI = –0.14 to –0.04, q-value = 0.004) in women with GDM, adjusted for potential confounders. In normoglycemic women, COVID-19 lockdown in late pregnancy was associated with higher fasting glucose level (β= 0.10, 95% CI = 0.08–0.12, q-value <0.0001), lower HDL-C level (β=–0.07, 95% CI = –0.08 to –0.04, q-value <0.0001), and increased risk of pregnancy-induced hypertension (adjusted OR=1.80, 95%CI=1.30–2.50, q-value=0.001). The fasting glucose level decreased less from early to late pregnancy in women who experienced COVID-19 lockdown than in the controls, regardless of the GDM status. The HDL-C has risen less with COVID-19 lockdown in the normoglycemic subgroup. In contrast, no significant differences regarding neonatal outcomes or infant weight were found between the two cohorts. Conclusion Experiencing the COVID-19 lockdown in pregnancy was associated with worse maternal metabolic status but similar neonatal outcomes and infant weight.

The relationship between online courses and mental health among Chinese children

Background Previous studies on the association of online courses and mental health were mainly conducted in universities, and no study investigated the relationship between characteristics of online courses and children’s mental health in primary and secondary school. This study aimed to explore the association of online courses and children’s mental health in primary and secondary school. Methods A cross-sectional study was conducted through an online survey among 540 primary and secondary school students and their parents in the eastern, central and western region of China from April to May in 2020. Children’s mental health was assessed by the Strengths and Difficulties Questionnaire (SDQ). Borderline mental health problems (SDQ total difficulties score ≥ 16) and mental health problems (SDQ total difficulties score ≥ 20) were defined according to Goodman’s standard. Multivariable linear and logistic regression models were used to examine the association between online courses and children’s mental health. Results Compared with those who did not have problems of online courses, children having the difficulty in understanding the content of online courses had a higher SDQ total difficulties score [β = 1.80, 95% confidence interval (CI): 0.89, 2.71] and a higher risk of borderline mental health problems [odds ratio (OR) = 1.93, 95%CI: 1.07, 3.49], while device or internet connection problems were not significantly associated with children’s mental health. Compared with children who had live courses, those having video-recorded courses had a higher SDQ total difficulties score (β = 0.90, 95%CI: 0.01, 1.80). Children who spent more than 4 h on online courses had a higher SDQ total difficulties score than those of less than or equal to 4 h (β = 0.95, 95%CI: 0.09, 1.81). Conclusion We found that online courses with inappropriate characteristics were associated with children’s mental health. The findings called for the efforts to optimize the online courses and improve children’s mental health. Supplementary Information The online version contains supplementary material available at 10.1186/s12888-022-03976-2.

Nasal irrigation efficiently attenuates SARS-CoV-2 Omicron infection, transmission and lung injury in the Syrian hamster model.

Recently, a new variant lineage of SARS-CoV-2, namely Omicron, became the dominant global circulating strain. The multiple antigenic mutations of Omicron largely decrease the efficiency of current vaccines and neutralizing antibodies, which highlights the need for more potent and reachable medical countermeasures. Here, we hypothesize that direct viral clearance by nasal irrigation might be a convenient and alternative option, and perform proof-of-concept experiments in the Syrian hamster model. Interestingly, Omicron shows a different dynamic in the changes of viral RNA, viral titers, and proinflammatory cytokines in nasal rinsing samples when compared with the prototype. Meanwhile, the levels of viral load and proinflammatory cytokines in nasal rinsing samples can indicate the severity of lung injury. Of note, daily nasal irrigation efficiently attenuates inflammation and lung injury in Omicron-infected hamsters by decreasing the viral loads in the respiratory tract organs. Moreover, daily nasal irrigation effectively suppresses viral transmission by close contact.

Catalytic cascade vapor-phase hydrotreatment of plastic waste into fuels and its sustainability assessment

The COVID-19 pandemic impacted the world through the anguish from a fast-spreading virus and by struggling with the increasing plastic waste. A catalytic cascade process where hydropyrolysis was coupled with downstream vapor-phase hydrotreatment was employed for the first time to upcycle real-world mixed plastic waste into drop-in fuels. This tandem vapor-phase hydrotreatment technology is feedstock-agnostic and therefore capable of upcycling different kinds of personal protective equipment (PPE) plastic waste into drop-in fuels over a non-noble bifunctional Ni/NiAl2O4 catalyst. A maximum 88.9 wt% single-pass yield of drop-in fuel-range hydrocarbons was obtained with a hydrotreatment temperature of 300 degrees C at 0.3 MPa H-2. Life cycle assessment showed that this catalytic cascade vapor-phase hydrotreatment approach had a high energy efficiency of 94%. The global warming potential of the obtained fuel could be reduced by 72% as a maximum in the low carbon future, compared with conventional fuel blends, indicating that it can be used as a promising chemical upcycling technology for achieving a sustainable plastic circular economy.

The relationship between online courses and mental health among Chinese children.

BACKGROUND: Previous studies on the association of online courses and mental health were mainly conducted in universities, and no study investigated the relationship between characteristics of online courses and children's mental health in primary and secondary school. This study aimed to explore the association of online courses and children's mental health in primary and secondary school. METHODS: A cross-sectional study was conducted through an online survey among 540 primary and secondary school students and their parents in the eastern, central and western region of China from April to May in 2020. Children's mental health was assessed by the Strengths and Difficulties Questionnaire (SDQ). Borderline mental health problems (SDQ total difficulties score ≥ 16) and mental health problems (SDQ total difficulties score ≥ 20) were defined according to Goodman's standard. Multivariable linear and logistic regression models were used to examine the association between online courses and children's mental health. RESULTS: Compared with those who did not have problems of online courses, children having the difficulty in understanding the content of online courses had a higher SDQ total difficulties score [ß = 1.80, 95% confidence interval (CI): 0.89, 2.71] and a higher risk of borderline mental health problems [odds ratio (OR) = 1.93, 95%CI: 1.07, 3.49], while device or internet connection problems were not significantly associated with children's mental health. Compared with children who had live courses, those having video-recorded courses had a higher SDQ total difficulties score (ß = 0.90, 95%CI: 0.01, 1.80). Children who spent more than 4 h on online courses had a higher SDQ total difficulties score than those of less than or equal to 4 h (ß = 0.95, 95%CI: 0.09, 1.81). CONCLUSION: We found that online courses with inappropriate characteristics were associated with children's mental health. The findings called for the efforts to optimize the online courses and improve children's mental health.

Upcycling disposable face masks into fuel range iso-alkanes through hydropyrolysis coupled with vapor-phase hydrocracking

The COVID-19 pandemic has resulted in an alarming accumulation of plastic waste. Herein, an integrated hydropyrolysis and hydrocracking process was performed to upcycle disposable masks into fuel-range iso-alkanes over carbon supported ruthenium (Ru/C). Experimental results indicated that catalyst type significantly affected product distribution during the hydropyrolysis and vapor-phase hydrocracking of disposable masks. Compared with zeolites-induced catalytic cascade process where up to ∼25.9 wt% yield of aromatic hydrocarbons such as toluene and xylenes were generated, a ∼82.7 wt% yield of desirable iso-alkanes with a high C5–C12 gasoline selectivity of 95.5% was obtained over Ru/C under 550 °C hydropyrolysis temperature and 300 °C hydrocracking temperature at 0.2 MPa H2. The cascade hydropyrolysis and hydrocracking process also exhibited high adaptability and flexibility in upcycling single-use syringes, food packaging, and plastic bags, generating 79.1, 81.6, and 80.3 wt% yields of fuel range iso/n-alkanes, respectively. This catalytic cascade hydrotreating process provides an efficient and effective approach to convert pandemic-derived plastic waste into gasoline-range fuel products.

Infection, pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile, adult and aged Syrian hamsters.

The new predominant circulating SARS-CoV-2 variant, Omicron, can robustly escape current vaccines and neutralizing antibodies. Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants, its pathogenicity in different age groups has not been well elucidated. Here, we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters, with more body weight loss, respiratory tract viral burden, and lung injury in these hamsters than in adult hamsters. Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection, whereas aged hamsters show excessive proinflammatory cytokine expression, delayed viral clearance, and aggravated lung injury. Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters. Overall, the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

Preferences of oral nutritional supplement therapy among postoperative patients with gastric cancer: Attributes development for a discrete choice experiment.

BACKGROUND: Adherence to oral nutritional supplement therapy among postoperative patients with gastric cancer is low. There is little knowledge about patients' priorities and needs regarding oral nutritional supplement therapy. The discrete choice experiment is an innovative method used to elicit patients' preferences. Good practice guidelines emphasize that the development of attributes and levels is a fundamentally important process. OBJECTIVE: To comprehensively describe the identification, refinement, and selection of attributes and levels for a discrete choice experiment. METHODS: A mixed-methods approach, consisting of three consecutive steps: a literature review, in-depth interviews, and focus groups. First, the literature review allowed quick identification of attributes and levels. Then, 15 in-depth interviews were conducted to gather a rich description of the experience of patients taking oral nutritional supplements after gastrectomy and to verify and enrich the attributes and levels list. Finally, four focus group participants discussed the wording of the attributes and levels and reduced the number of attributes to manageable numbers through voting ranking methods. RESULTS: Following the literature review and qualitative data collection, eight attributes were finally generated, each with two to three levels. The following attributes were included: 1) information provider; 2) health guidance approach; 3) adverse reactions; 4) flavor; 5) follow-up method; 6) follow-up frequency; 7) psychological support; 8) cost. These attributes covered the important attributes of nutritional preparations and health guidance included in ONS therapy that were relevant to patients. CONCLUSIONS: This study's mixed-methods approach has been found highly suitable to identify, refine and select attributes and levels for a discrete choice experiment. The three methods have pros and cons, and they complement each other, especially the analysis of qualitative data led to a deeper and broader understanding of attributes and levels.

Sleep health, its intraindividuality, and perceived stress in college students during the COVID-19 pandemic.

Objective: To describe the changes in sleep health domains and examine the associations between the repeated measures and intraindividual variability (IIV) of these domains and perceived stress. Participants: A diverse racial and ethnic group of first-year college students (N = 23, 78.3% female, aged 17-18) attending in-person classes during the COVID-19 pandemic. Methods: Sleep health domains were determined using 7-day wrist actigraph and daily sleep diaries, and perceived stress scale was completed at 1-month intervals across 3 months. Results: Sleep timing, regularity, and alertness during daytime demonstrated statistically significant changes between three timepoints. Greater stress was associated with more irregularity (B = 2.25 [.87-3.62], p < .001), more dissatisfaction in sleep (B = .04 [.02-.19], p < .01), alertness during daytime (B = .18 [.05-.31], p < .001), and greater IIV (ie, fluctuations) in sleep satisfaction (B = .083 [.02, .15], p < .01). Conclusion: These findings offer insights for future researchers to facilitate intervention development to promote mental and sleep health among college students.

Sex differences in comorbidities and COVID-19 mortality-Report from the real-world data.

Background: The differential effect of comorbidities on COVID-19 severe outcomes by sex has not been fully evaluated. Objective: To examine the association of major comorbidities and COVID-19 mortality in men and women separately. Methods: We performed a retrospective cohort analysis using a large electronic health record (EHR) database in the U.S. We included adult patients with a clinical diagnosis of COVID-19 who also had necessary information on demographics and comorbidities from January 1, 2016 to October 31, 2021. We defined comorbidities by the Charlson Comorbidity Index (CCI) using ICD-10 codes at or before the COVID-19 diagnosis. We conducted logistic regressions to compare the risk of death associated with comorbidities stratifying by sex. Results: A total of 121,342 patients were included in the final analysis. We found significant sex differences in the association between comorbidities and COVID-19 death. Specifically, moderate/severe liver disease, dementia, metastatic solid tumor, and heart failure and the increased number of comorbidities appeared to confer a greater magnitude of mortality risk in women compared to men. Conclusions: Our study suggests sex differences in the effect of comorbidities on COVID-19 mortality and highlights the importance of implementing sex-specific preventive or treatment approaches in patients with COVID-19.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.