Remote Blood Oxygen Estimation From Videos Using Neural Networks.

Peripheral blood oxygen saturation (SpO 2) is an essential indicator of respiratory functionality and received increasing attention during the COVID-19 pandemic. Clinical findings show that COVID-19 patients can have significantly low SpO 2 before any obvious symptoms. Measuring an individual's SpO 2 without having to come into contact with the person can lower the risk of cross contamination and blood circulation problems. The prevalence of smartphones has motivated researchers to investigate methods for monitoring SpO 2 using smartphone cameras. Most prior schemes involving smartphones are contact-based: They require using a fingertip to cover the phone's camera and the nearby light source to capture reemitted light from the illuminated tissue. In this paper, we propose the first convolutional neural network based noncontact SpO 2 estimation scheme using smartphone cameras. The scheme analyzes the videos of an individual's hand for physiological sensing, which is convenient and comfortable for users and can protect their privacy and allow for keeping face masks on. We design explainable neural network architectures inspired by the optophysiological models for SpO 2 measurement and demonstrate the explainability by visualizing the weights for channel combination. Our proposed models outperform the state-of-the-art model that is designed for contact-based SpO 2 measurement, showing the potential of the proposed method to contribute to public health. We also analyze the impact of skin type and the side of a hand on SpO 2 estimation performance.

Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.

Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We demonstrated that SYK inhibition was associated with reduced neutrophil activation, increased circulation of mature neutrophils (CD10+CD33-), and decreased circulation of low-density granulocytes and polymorphonuclear myeloid-derived suppressor cells (HLA-DR-CD33+CD11b-). SYK inhibition was also associated with normalization of transcriptional activity in circulating monocytes relative to healthy controls, an increase in frequency of circulating nonclassical and HLA-DRhi classical monocyte populations, and restoration of interferon responses. Together, these data suggest that SYK inhibition may mitigate proinflammatory myeloid cellular and soluble mediator responses thought to contribute to immunopathogenesis of severe COVID-19.

Interpretation of the prevention and treatment of COVID-19 in Jiangxi based on "unified coldness and warmness"

Since the outbreak of COVID-19, various regions have introduced their own TCM prevention and treatment methods. However, there are two opposing views on the nature of coldness and warmness. With advanced social development, the thought of the unification of coldness and warmness has developed rapidly, and many doctors gradually have realized the importance and practicability of the unification of coldness and warmness, and began to advocate the unification of coldness and warmness syndrome. The prevention and treatment of COVID-19 in Jiangxi was developed by Professor Wu Bingcai,a master of Chinese medicine, based on the unified idea of cold and temperature, according to the characteristics of humid climate in Jiangxi, and in combination with the characteristics of COVID-19, the anti-toxin prescription for dispelling cold and desiccating dampness and the anti-toxin prescription for clearing heat and dehumidifying, which achieved exact and satisfactory results in clinical application.

A Cross-Sectional Survey of National Chinese College Students' Mental Status during COVID-19 Pandemic: Using a Compiled Stress Response Questionnaire.

As the coronavirus disease (COVID-19) spread, local governments in China adopted severe lockdown measures to control the pandemic. People were restricted from traveling for leisure, business, education, and medical treatment. Changes were observed in people's psychological states as a result of COVID-19. This study aimed to construct a Stress Response Questionnaire based on the stress response theory for use with college students, to access their authentic mental health conditions and provide psychological intervention suggestions and countermeasures for the emergency plan formulated by the education department. The questionnaire was used to collect responses from a sample of 16,353 college students from 34 provinces in China. The results showed that anxiety levels varied by sex, current location, and pandemic region, each of which predicted different levels of emotional disturbance. Thus, we highly recommend that the Chinese college administration implement appropriate intervention programs and procedures to help college students maintain their mental health.

Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities.

Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) will have greater value as an important diagnostic tool. An in-depth analysis and understanding of the metrics derived from WWS is required to interpret and utilize WWS-acquired data effectively (McClary-Gutierrez et al., 2021; O'Keeffe, 2021). In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven cities in Canada over periods ranging from 8 to 21 months. This work demonstrates that significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing (resulting in a reduction to testing access and a reduction in the number of daily tests) in these communities, despite increases in the wastewater signal. Furthermore, the WC ratio decreased significantly in 6 of the 7 studied locations, serving as a potential signal of the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized community (40-60 % allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized community (40-60 % allelic proportion). Finally, a significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variant's greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when community immunity was high. The WC ratio, used as an additional monitoring metric, could complement clinical case counts and wastewater signals as individual metrics in its potential ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ±â€…0.3 vs -2.6 ±â€…0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.

Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease.

BACKGROUND: Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. METHODS: Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. RESULTS: The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1/Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. CONCLUSIONS: Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1.

Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease.

BACKGROUND: Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. METHODS: Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. RESULTS: The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1/Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. CONCLUSIONS: Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1.

Near real-time determination of B.1.1.7 in proportion to total SARS-CoV-2 viral load in wastewater using an allele-specific primer extension PCR strategy.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives to date. Antigenic drift has resulted in viral variants with putatively greater transmissibility, virulence, or both. Early and near real-time detection of these variants of concern (VOC) and the ability to accurately follow their incidence and prevalence in communities is wanting. Wastewater-based epidemiology (WBE), which uses nucleic acid amplification tests to detect viral fragments, is a reliable proxy of COVID-19 incidence and prevalence, and thus offers the potential to monitor VOC viral load in a given population. Here, we describe and validate a primer extension PCR strategy targeting a signature mutation in the N gene of SARS-CoV-2. This allows quantification of B.1.1.7 versus non-B.1.1.7 allele frequency in wastewater without the need to employ quantitative RT-PCR standard curves. We show that the wastewater B.1.1.7 profile correlates with its clinical counterpart and benefits from a near real-time and facile data collection and reporting pipeline. This assay can be quickly implemented within a current SARS-CoV-2 WBE framework with minimal cost; allowing early and contemporaneous estimates of B.1.1.7 community transmission prior to, or in lieu of, clinical screening and identification. Our study demonstrates that this strategy can provide public health units with an additional and much needed tool to rapidly triangulate VOC incidence/prevalence with high sensitivity and lineage specificity.

COVID-19 wastewater surveillance in rural communities: Comparison of lagoon and pumping station samples.

Wastewater-based epidemiology/wastewater surveillance has been a topic of significant interest over the last year due to its application in SARS-CoV-2 surveillance to track prevalence of COVID-19 in communities. Although SARS-CoV-2 surveillance has been applied in more than 50 countries to date, the application of this surveillance has been largely focused on relatively affluent urban and peri-urban communities. As such, there is a knowledge gap regarding the implementation of reliable wastewater surveillance in small and rural communities for the purpose of tracking rates of incidence of COVID-19 and other pathogens or biomarkers. This study examines the relationships existing between SARS-CoV-2 viral signal from wastewater samples harvested from an upstream pumping station and from an access port at a downstream wastewater treatment lagoon with the community's COVID-19 rate of incidence (measured as percent test positivity) in a small, rural community in Canada. Real-time quantitative polymerase chain reaction (RT-qPCR) targeting the N1 and N2 genes of SARS-CoV-2 demonstrate that all 24-h composite samples harvested from the pumping station over a period of 5.5 weeks had strong viral signal, while all samples 24-h composite samples harvested from the lagoon over the same period were below the limit of quantification. RNA concentrations and integrity of samples harvested from the lagoon were both lower and more variable than from samples from the upstream pumping station collected on the same date, indicating a higher overall stability of SARS-CoV-2 RNA upstream of the lagoon. Additionally, measurements of PMMoV signal in wastewater allowed normalizing SARS-CoV-2 viral signal for fecal matter content, permitting the detection of actual changes in community prevalence with a high level of granularity. As a result, in sewered small and rural communities or low-income regions operating wastewater lagoons, samples for wastewater surveillance should be harvested from pumping stations or the sewershed as opposed to lagoons.

Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary end point was serologic response to HepB-CpG (anti-hepatitis B surface antibodies ≥10 mIU/mL) and RZV (≥fourfold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8%; 95% confidence interval [CI], 0.7-18.9) than patients who were TN (28.1%; 95% CI, 15.6-45.4; P = .017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5%; 95% CI, 27.8-56.6) and TN cohorts (59.1%; 95% CI, 38.7-76.7; P = .2). BTKi's were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. These trials were registered at www.clinicaltrials.gov as #NCT03685708 (Hep-CpG) and #NCT03702231 (RZV).

The impact of the COVID-19 pandemic on pediatric operations: a retrospective study of Chinese children.

BACKGROUND: The aim of this study was to quantify the impact of coronavirus disease 2019 (COVID-19) on pediatric operations, and establish preoperative, intraoperative, and postoperative protocols to improve the pediatric operations. METHODS: We here compare the number of patients who underwent surgery in Chongqing Medical University Affiliated Children's Hospital during the pandemic (January 23-March 11), after the pandemic (March 12-April 30), after our measures were put in place (May 1-May 21), and the equivalent period in 2019. RESULT: During the COVID-19 pandemic, 62.68% fewer patients underwent surgery than during the homologous period of time 1 year earlier (P < 0.01). After the COVID-19 pandemic, the number of orchidopexy cases increased significantly from 175.14 to 504.57 per week (P < 0.01). The large number of patients that accrued in our hospital may have increased the risk of COVID-19 transmission. In response, hospitals and clinics have made protocols and reorganized healthcare facilities (e.g., performing nucleic acid tests (NAT), adding adequate personal protective equipment (PPE)) from May 1, 2020. After the measures were implemented, the number of operations performed remained stable and comparable to the pre-pandemic period. COVID-19 RNA detection was performed in 5104 cases and there were no new confirmed cases in our hospital. CONCLUSION: This outbreak of COVID-19 has affected not only individuals with COVID-19 but also patients seeking surgical operations. Understanding the present situation helps clinicians provide a high level of treatment to all children.