Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs.

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.

User-Centered Design and Implementation of an Interoperable FHIR Application for Pediatric Pneumonia Prognostication in a Randomized Trial.

OBJECTIVE: To support a pragmatic, electronic health record (EHR)-based randomized controlled trial, we applied user-centered design (UCD) principles, evidence-based risk communication strategies, and interoperable software architecture to design, test, and deploy a prognostic tool for children in emergency departments (EDs) with pneumonia. METHODS: Risk for severe in-hospital outcomes was estimated using a validated ordinal logistic regression model to classify pneumonia severity. To render the results usable for ED clinicians, we created an integrated SMART on FHIR web application built for interoperable use in two pediatric EDs using different EHR vendors: Epic and Cerner. We followed a UCD framework, including problem analysis and user research, conceptual design and early prototyping, user interface development, formative evaluation, and post-deployment summative evaluation. RESULTS: Problem analysis and user research from 39 clinicians and nurses revealed user preferences for risk aversion, accessibility, and timing of risk communication. Early prototyping and iterative design incorporated evidence-based design principles, including numeracy, risk framing, and best-practice visualization techniques. After rigorous unit and end-to-end testing, the application was successfully deployed in both EDs, which facilitatd enrollment, randomization, model visualization, data capture, and reporting for trial purposes. CONCLUSIONS: The successful implementation of a custom application for pneumonia prognosis and clinical trial support in two health systems on different EHRs demonstrates the importance of UCD, adherence to modern clinical data standards, and rigorous testing. Key lessons included the need for understanding users' real-world needs, regular knowledge management, application maintenance, and the recognition that FHIR applications require careful configuration for interoperability.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Tunnel-Oriented VO2 (B) Cathode for High-Rate Aqueous Zinc-Ion Batteries.

Tunnel-type vanadium oxides are promising cathodes for aqueous zinc ion batteries. However, unlike layer-type cathodes with adjustable layer distances, enhancing ion-transport kinetics in tunnels characterized by fixed sizes poses a considerable challenge. This study highlights that the macroscopic arrangement of the electrode crucially determines tunnel orientation, thereby influencing ion transport. By changing the material morphology, the tunnel orientation can be optimized to facilitate rapid ion diffusion. In a proof-of-concept demonstration, it is revealed that (00l) facets-dominated VO2 (B) nanobelts with dispersive morphology (VO2-D) tend to adopt a stacking pattern with directional ion transport along the c-axis on the electrode and guarantee fast ion diffusion. Compared with the aggregated sample (VO2-A) that tends to random arrangement on the electrode with isotropic and slow ion transfer behavior, the electrode featuring dispersive (00l) facets-dominated VO2 (B) nanobelts displays directional and fast ion diffusion behavior, thus exhibits an ultrahigh-rate performance (420.8 and 344.8 mAh g-1 at 0.1 and 10 A g-1, respectively) and long cycling stability (84.3% capacity retention under 5000 cycles at 10 A g-1). The results suggest that simultaneous manipulation of exposed crystal facet and morphology-related electrode arrangement should be promising for boosting the ion-transport kinetics in tunnel-type vanadium oxide cathodes.

Ultrastable Iodinated Oil-Based Pickering Emulsion Enables Locoregional Sustained Codelivery of Hypoxia Inducible Factor-1 Inhibitor and Anticancer Drugs for Tumor Combination Chemotherapy.

Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis.

BACKGROUND: Prolonged SARS-CoV-2 infections in people who are immunocompromised might predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection have not been systematically investigated. We aimed to assess risk factors for prolonged SARS-CoV-2 infection and associated intrahost evolution. METHODS: In this multicentre, prospective analysis, participants were enrolled at five US medical centres. Eligible patients were aged 18 years or older, were SARS-CoV-2-positive in the previous 14 days, and had a moderately or severely immunocompromising condition or treatment. Nasal specimens were tested by real-time RT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. FINDINGS: From April 11, 2022, to Oct 1, 2022, 156 patients began the enrolment process, of whom 150 were enrolled and included in the analyses. Participants had B-cell malignancy or anti-B-cell therapy (n=18), solid organ transplantation or haematopoietic stem-cell transplantation (HSCT; n=59), AIDS (n=5), non-B-cell malignancy (n=23), and autoimmune or autoinflammatory conditions (n=45). 38 (25%) participants were real-time RT-PCR-positive and 12 (8%) were culture-positive 21 days or longer after initial SARS-CoV-2 detection or illness onset. Compared with the group with autoimmune or autoinflammatory conditions, patients with B-cell dysfunction (adjusted hazard ratio 0·32 [95% CI 0·15-0·64]), solid organ transplantation or HSCT (0·60 [0·38-0·94]), and AIDS (0·28 [0·08-1·00]) had longer duration of infection, defined as time to last positive real-time RT-PCR test. There was no significant difference in the non-B-cell malignancy group (0·58 [0·31-1·09]). Consensus de novo spike mutations were identified in five individuals who were real-time RT-PCR-positive longer than 56 days; 14 (61%) of 23 were in the receptor-binding domain. Mutations shared by multiple individuals were rare (<5%) in global circulation. INTERPRETATION: In this cohort, prolonged replication-competent omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting longer than 56 days accumulated spike mutations, which were distinct from those seen globally. Populations at high risk should be targeted for repeated testing and treatment and monitored for the emergence of antiviral resistance. FUNDING: US Centers for Disease Control and Prevention.

Characterization of the physicochemical properties of Lipu Colocasia esculenta (L.) Schott starch: A potential new food ingredient.

The physicochemical properties of Lipu taro starch (LTS), cassava starch (CS) and wheat starch (WS) were analyzed. These starches exhibited a comparable starch content (86 %). However, LTS had a significantly lower amylose content (15.93 %) compared to CS (26.62 %) and WS (33.53 %). Moreover, LTS demonstrated an irregular polygonal cubic morphology with a smaller particle size of 2.55 µm while possessed an A-type crystal structure with high crystallinity at 25.07 %. In contrast, CS and WS had larger particle sizes of 13.33 µm and 16.68 µm, respectively, with lower crystallinities of 22.52 % and 20.33 %. Due to these physicochemical properties, LTS exhibited superior emulsification properties with a higher emulsifying activity index of 8.63 m2/g and an emulsion stability index of 69.18 min, whereas CS and WS had values of 2.35 m2/g and 25.15 min, and 0.37 m2/g and 11.48 min, respectively. LTS also demonstrated enhanced thermal stability, characterized by higher gelatinization temperature (indicated by To, Tp, Tc, and ΔT) and reduced paste viscosity (indicated by PV, TV, FV, SBV, and BDV) compared to CS. However, the mechanical strength of the gel made from LTS (indicated by hardness, adhesiveness, springiness, gumminess, and chewiness) was comparatively inferior to those from CS and WS.

Molecular mechanisms and physiological responses of rice leaves co-exposed to submicron-plastics and cadmium: Implication for food quality and security.

The effects of co-exposure to aged submicron particles (aSMPs) and Cd as model contaminants on rice leaves via the foliar route were investigated. Thirty-day-old rice seedlings grown in soil were exposed to Cd (nitrate) through foliar spraying at concentrations of 1, 10, 50, 100, and 500 µM, with or without aSMP at a rate of 30 µg d-1. It was observed that Cd translocated from leaves to roots via stems even without co-exposure to SMP. Co-exposure can reduce cadmium levels in leaves. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis confirmed a significant reduction (29.3 - 77.9%) in Cadmium accumulation in the leaves of rice plants during co-exposure. Exposure to Cd resulted in physiological, transcriptomic, and metabolomic changes in rice leaves, disrupting 28 metabolism pathways, and impacting crop yield and quality. Exposure to both Cd and aSMPs can interfere with the Cd distribution in plants. Rice leaves exposed solely to Cd exhibit higher toxicity and Cd accumulation, compared to those co-exposed to Cd and aSMPs. The accumulation of Cd in plant leaves is enhanced with aSMPs, which may lead to more pronounced gene expression regulation and changes in metabolic pathways, compared to Cd exposure. Our study found that the independent Cd exposure group had higher Cd accumulation and toxicity in rice leaves compared to the combined exposure of Cd and aSMPs. We hypothesize that aged negatively charged SMPs can capture Cd and reduce its exposure in the free state while jointly inhibiting Cd-induced oxidative and chloroplast damage, thereby reducing the potential risk of Cd exposure in rice plants.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Sex differences in COVID-19 symptom severity and trajectories among ambulatory adults.

Background: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood. Methods: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model. Results: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males (p < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed. Conclusions: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males.

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

SARS-CoV-2 shedding and evolution in immunocompromised hosts during the Omicron period: a multicenter prospective analysis.

Background: Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear. Methods: Adults aged ≥18 years were enrolled at 5 hospitals and followed from 4/11/2022 - 2/1/2023. Eligible patients were SARS-CoV-2-positive in the previous 14 days and had a moderate or severely immunocompromising condition or treatment. Nasal specimens were tested by rRT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. Results: We enrolled 150 patients with: B cell malignancy or anti-B cell therapy (n=18), solid organ or hematopoietic stem cell transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) were rRT-PCR-positive and 12 (8%) were culture-positive ≥21 days after initial SARS-CoV-2 detection or illness onset. Patients with B cell dysfunction had longer duration of rRT-PCR-positivity compared to those with autoimmune/autoinflammatory conditions (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations were identified in 5 individuals who were rRT-PCR-positive >56 days; 61% were in the receptor-binding domain (RBD). Mutations shared by multiple individuals were rare (<5%) in global circulation. Conclusions: In this cohort, prolonged replication-competent Omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting >56 days accumulated spike mutations, which were distinct from those seen globally.

Sludge-derived iron-carbon material enhancing the removal of refractory organics in landfill leachate: Characteristics optimization, removal mechanism, and molecular-level investigation.

Mature landfill leachate is a refractory organic wastewater, and needs physical and chemical pretreatments contemporaneously, e.g. iron-carbon micro-electrolysis (IC-ME). In this study, a novel iron-carbon (Fe-C) material was synthesized from waste activated sludge to be utilized in IC-ME for landfill leachate treatment. The pyrolysis temperature, mass ratio of iron to carbon, and solid-liquid ratio in leachate treatment were optimized as 900 °C with 1.59 and 34.7 g/L. Under these optimal conditions, the chemical oxygen demand (COD) removal efficiency reached 79.44 %, which was 2.6 times higher than that of commercial Fe-C material (30.1%). This excellent COD removal performance was indicated to a better mesoporous structure, and uniform distribution of zero-valent iron in novel Fe-C material derived from sludge. The contribution order of COD removal in IC-ME treatment for landfill leachate was proven as coagulation, adsorption, and redox effects by a contrast experiment. The removal of COD includes synthetic organic compounds, e.g. carcinogens, pharmaceuticals and personal care products. The contents of CHO, CHON, and CHOS compounds of dissolved organic matter (DOM) in the leachate were decreased, and both the molecular weight and unsaturation of lipids, lignin, and tannic acids concentration were also reduced. Some newly generated small molecular DOM in the treated leachate further confirmed the existence of the redox effect to degrade DOM in leachate. The total cost of sludge-derived Fe-C material was only USD$ 152.8/t, which could save 76% of total compared with that of commercial Fe-C materials. This study expands the prominent source of Fe-C materials with excellent performance, and deepens the understanding of its application for leachate treatment.

Estimating the Burden of Influenza Hospitalizations Across Multiple Seasons Using Capture-Recapture.

INTRODUCTION: Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. METHODS: Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-17 through 2019-20. EIP identified cases through surveillance of laboratory results for hospitalized children and adults. HAIVEN and NVSN recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. RESULTS: Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10,000 persons in 2016-17 to 40 per 10,000 persons in 2017-18. Adults age ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10,000 persons during the 2017-18 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. CONCLUSION: Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates.

Validation of Childhood Pneumonia Prognostic Models for Use in Emergency Care Settings.

BACKGROUND: Unwarranted variation in disposition decisions exist among children with pneumonia. We validated three prognostic models for predicting pneumonia severity among children in the emergency department (ED) and hospital. METHODS: We performed a two-center, prospective study of children 6 months to <18 years presenting to the ED with pneumonia from January 2014 to May 2019. We evaluated three previously developed disease-specific prognostic models which use demographic, clinical, and diagnostic predictor variables, with each model estimating risk for Very Severe (mechanical ventilation or shock), Severe (ICU without very severe features), and Moderate/Mild (Hospitalization without severe features or ED discharge) pneumonia. Predictive accuracy was measured using discrimination (concordance or c-statistic) and re-calibration. RESULTS: There were 1088 children included in one or more of the three models. Median age was 3.6 years and the majority of children were male (53.7%) and identified as non-Hispanic White (63.7%). The distribution for the ordinal severity outcome was mild or moderate (79.1%), severe (15.9%), and very severe (4.9%). The three models each demonstrated excellent discrimination (C-statistic range across models [0.786-0.803]) with no appreciable degradation in predictive accuracy from the derivation cohort. CONCLUSIONS: All three prognostic models accurately identified risk for three clinically meaningful levels of pneumonia severity and demonstrated very good predictive performance. Physiologic variables contributed the most to model prediction. Application of these objective tools may help standardize and improve disposition and other management decisions for children with pneumonia.

Early efficacy of postoperative rehabilitation training for lumbar disc herniation.

OBJECTIVE: To investigate the early clinical efficacy of rehabilitation training after unilateral biportal endoscopy for lumbar disc herniation and to analyze the prognostic factors. METHODS: A total of 100 patients with lumbar disc herniation who underwent unilateral biportal endoscopy at The Sixth Affiliated Hospital of Nantong University from January 2019 to January 2021 were retrospectively analyzed. The control group was given a standard home-based exercise program, while the intervention group was given a substituted rehabilitation training opposed to a standard home-based exercise program. The early postoperative pain relief and quality of life values were compared between the two groups, and the independent risk factors affecting the prognosis of patients were analyzed. RESULTS: There were no significant differences in sex, age, smoking, drinking, BMI, course of disease, type of disc herniation, preoperative VAS, ODI or SF-36 between the two groups (P > 0.05). There was no significant difference in preoperative and postoperative VAS and ODI scores at 3 months between the two groups (P > 0.05), yet there were significant differences in postoperative VAS and ODI at 12 months (P < 0.05). The SF-36 score of the intervention group was lower than that of the control group at 12 months, and the difference was statistically significant (P < 0.05). The excellent rate of the Macnab standard modification used in the intervention group was 88.00% at 12 months, and that in the control group was 62.00%. The difference between the two groups was considered to indicate a statistically significant (P < 0.05). The results of logistic multivariate regression model analysis showed that rehabilitation training (95% CI: 1.360-12.122, P = 0.012), the type of intervertebral disc (95% CI: 0.010-0.676, P = 0.020), and age (95% CI: 1.056-8.244, P = 0.039) were independent risk factors affecting the prognosis of patients. CONCLUSION: Postoperative rehabilitation training can effectively relieve pain and improve quality of life; thus, it is highly recommended in the clinic. Postoperative rehabilitation training, intervertebral disc type and age are independent risk factors for the postoperative prognosis of lumbar intervertebral disc herniation.