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IntroductionAntiretroviral treatment regimens can effectively control HIV replication and some aspects of disease progression. However, molecular events in end-organ diseases such as central nervous system (CNS) disease are not yet fully understood, and routine eradication of latent reservoirs is not yet in reach. Brain tissue-derived extracellular vesicles (bdEVs) act locally in the source tissue and may indicate molecular mechanisms in HIV CNS pathology. Regulatory RNAs from EVs have emerged as important participants in HIV disease pathogenesis. Using brain tissue and bdEVs from the simian immunodeficiency virus (SIV) model of HIV disease, we profiled messenger RNAs (mRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), seeking to identify possible networks of RNA interaction in SIV infection and neuroinflammation.MethodsPostmortem occipital cortex tissue were collected from pigtailed macaques: uninfected controls and SIV-infected subjects (acute phase and chronic phase with or without CNS pathology). bdEVs were separated and characterized in accordance with international consensus standards. RNAs from bdEVs and source tissue were used for sequencing and qPCR to detect mRNA, miRNA, and circRNA levelsResultsMultiple dysregulated bdEV RNAs, including mRNAs, miRNAs, and circRNAs, were identified in acute infection and chronic infection with pathology. Most dysregulated mRNAs in bdEVs reflected dysregulation in their source tissues.These mRNAs are disproportionately involved in inflammation and immune responses, especially interferon pathways. For miRNAs, qPCR assays confirmed differential abundance of miR-19a-3p, let-7a-5p, and miR-29a-3p (acute SIV infection), and miR- 146a-5p and miR-449a-5p (chronic with pathology) in bdEVs. In addition, target prediction suggested that several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in small RNA levels in bdEVs during SIV infection.ConclusionsRNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use between October and December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance.

Blood transfusions are among the most common therapeutic procedures performed in hospitalized patients. This study evaluates contemporary national trends in red blood cell (RBC), plasma, platelet, and cryoprecipitate transfusions. National Inpatient Sample, the largest all-payer inpatient database representing 94% to 97% of the US population, was evaluated from the fourth quarter (Q4) of 2015 through 2018. Quarterly trends for the percentage of hospitalizations with a transfusion procedure were separately examined for each blood product using log binomial regression and reported as quarterly percent change (QPC). The percentage of hospitalizations with an RBC transfusion decreased from 4.22% (2015Q4) to 3.79% (2018Q4) (QPC = −0.72; 95% confidence interval [CI], −1.26 to −0.19; Ptrend = .008). Although plasma transfusions also decreased, QPC = −1.33 (95% CI, −2.00 to −0.65; Ptrend < .001), platelet transfusions remained stable QPC = −0.13 (95% CI, −0.99 to 0.73; Ptrend = .766). In contrast, hospitalizations with cryoprecipitate utilization significantly increased QPC = 2.01 (95% CI, 0.57 to 3.44; Ptrend = .006). Significant quarterly reductions in RBC transfusions were also seen among many, but not all, strata of sex, race/ethnicity, patient risk severity, and admission type (elective vs nonelective). Despite significant declines in RBC transfusions among older adults, there were no significant changes among pediatric age-group (

Background Lyme disease (LD) and babesiosis are increasing in the United States. We sought to characterize and compare their epidemiology and health burden using a nationally representative sample of hospitalizations. Methods Data were extracted from the National Inpatient Sample (NIS) pertaining to LD and babesiosis for 2018 and 2019. The NIS is a comprehensive database of all-payer inpatient hospitalizations, representing a stratified systematic random sample of discharges from US hospitals. Patient demographics, clinical outcomes, and admission costs were evaluated, in addition to hospital-level variables (eg, location/teaching status and census division). Annual incidence of hospitalizations was calculated using US Census Bureau data. Results The annual incidence of hospitalizations of LD-related and babesiosis-related hospitalizations were 6.98 and 2.03 per 1 000 000 persons/year. Of the 4585 LD hospitalizations in 2018–2019, 60.9% were among male patients, 85.3% were White, and 39.0% were ≥60 years. Of the 1330 babesiosis hospitalizations in 2018–2019, 72.2% were among male patients, 78.9% were White, and 74.1% were ≥60 years; 70.0% of LD and 91.7% of babesiosis hospitalizations occurred in Middle Atlantic or New England. Lower disease severity was noted in 81.8% of LD hospitalizations compared with 49.3% of babesiosis hospitalizations, whereas those suffering from high severity were 2.3% and 6.0%, respectively. The mean hospital charges for LD and babesiosis hospitalizations were $33 440.8 and $40 689.8, respectively. Conclusions Despite overlap between the 2 diseases, LD has a broader geographic range and a greater number of hospital admissions, whereas babesiosis is more severe, incurring longer hospital stays, higher inpatient costs, and deaths.

It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID-19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers.The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay.TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS-CoV-2.There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non-pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.

BACKGROUND: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients. METHODS: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion. RESULTS: There were 168,315 ED visits and 58,815 hospitalizations (age = 18–90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18–24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95% CI:4.15–5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10–2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission. CONCLUSIONS: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.

Two analogue small molecules, BDTP-2F with a difluorobenzene π-bridge and BDTP-4F with a tetrafluorobenzene π-bridge, are designed to investigate the impact of a fluorine substituted π-bridge on photovoltaic performance.

Currently, rational design of polymer acceptors is desirable but there is still a challenge to develop high-performance all-polymer solar cells (all-PSCs). In this work, brominated thienyl-fused malononitrile-based monomer is employed to copolymerize with indacenodithiophene (IDT) and benzodithiophene (BDT)-based linking units to develop two polymerized small molecule acceptors (PSMAs) PIDT and PBDT, respectively, for all-PSCs. The two PSMAs show similar absorption edges, while PBDT shows a slightly higher lowest unoccupied molecular orbital (LUMO) energy level than PIDT. Benefitted from the relatively high LUMO levels of the two polymer acceptors, notable open-circuit voltage (V

Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination.A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons.In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates0.05).A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs.

Data from the National Inpatient Sample demonstrate that methicillin-resistant Staphylococcus aureus (MRSA)–related septicemia hospitalizations increased from 1.67 (95% CI, 1.63–1.72) to 1.94 (95% CI, 1.88–2.00; Ptrend

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

Data from the National Inpatient Sample indicate that Clostridioides difficile prevalence decreased from 10.1 (95% confidence interval [CI] = 9.9–10.3) to 8.6 (95% CI = 8.5–8.8) per 1000 hospital discharges between 2016 and 2018, after accounting for age, sex, and race. There was heterogeneity in the prevalence and decrease in prevalence by geographic region in the United States.

Serologic, point-of-care tests to detect antibodies against SARS-CoV-2 are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a new method of COVID-19 antibody testing employing hemagglutination tested on a dry card, similar to that which is already available for rapid typing of ABO blood groups. A fusion protein linking red blood cells (RBCs) to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was placed on the card. 200 COVID-19 patient and 200 control plasma samples were reconstituted with O-negative RBCs to form whole blood and added to the dried protein, followed by a stirring step and a tilting step, 3-minute incubation, and a second tilting step. The sensitivity for the hemagglutination test, Euroimmun IgG ELISA test and RBD-based CoronaChek lateral flow assay was 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing pre-pandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (p

Background The efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors. Methods A cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher’s exact and Wilcoxon rank-sum tests, respectively. Results Among CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38–50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A (P Conclusions Heterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.

Modern production systems are the carriers that advanced manufacturing technologies can be realized. Accurate health state evaluation is the basis for ensuring stable operation of the production system and developing a maintenance strategy However, the most existing health evaluation techniques of production systems are based on the single source data. The multi-source data based hidden Markov model is proposed to evaluate health state (including machine performance data, process quality data, etc.). The operational features-based health definition of the production system of production systems is proposed. The modeling process of hidden Markov model based on multi-source data is given, and the multi-performance degradation law of production system is revealed. And taking the pre-grinding gear hob production system as an example, the accuracy and superiority of this proposed approach are verified.

With the increase in demand for metal resources, research on deep-sea polymetallic nodule mining has been reinvigorated, but the problem of its environmental impact cannot be ignored. No matter what method is used for mining, it will disturb the surface sediments of the seabed, thereby increasing the concentration of suspended solid particles and metal ions in the water body, changing the properties of the near-bottom water body and sediments, and affecting biological activity and the living environment. Focusing on the ecological and environmental impacts of deep-sea polymetallic nodule mining, taking as our main subject of focus the dynamic changes in sediments, we investigated the environmental impacts of nodule mining and their relationships with each other. On this basis, certain understandings are summarized relating to the ecological and environmental impacts of deep-sea polymetallic nodule mining, based on changes in the engineering geological properties of sediment, and solutions for current research problems are proposed.

This study assesses HIV and hepatitis C testing and treatment availability in US specialty substance use disorder treatment facilities that offered medication for opioid use disorder in 2017-2020, stratified between federally certified Opioid Treatment Programs (OTPs) and non-OTPs.

A polyvinyl chloride (PVC) membrane sensor was developed to accurately detect beef taste quality grades. The beef taste was identified by the Fisher discriminant and verified by sensory evaluation. The PVC membrane sensor with the maximum open circuit potential (OCP) value and excellent performance was composed of 0.4 mL of dibutyl phthalate (DBP), 0.25 mL of lauryl ether phosphate, 3.6 mg of magnesium stearate and 6 mg of thermoplastic polyurethanes (TPU). Texture analyzer tests showed that the membranes showed desired physical properties, and the elasticity, viscosity and cohesion of the PVC membrane sensor were 4.74 mm, 2.17 mJ and 1.89 respectively. Scanning electron microscopy (SEM) showed the electrode immersed for 6 h without separation with PVC membrane. The coefficient of variation was less than 10% with a storage period of 7 months. Sensory evaluation showed that the beef sensory rated grades array determination by the Fisher discriminant method to verify the sensitivity of ammonia-sensitive substance-modified PVC membrane sensor had an accuracy of 93.3%.

Geotechnical problems in extremely complex environments have become increasingly prominent, which raises the need to explore more efficient solutions. Multidisciplinary approaches show a new perspective to deal with these problems. In this study, the electrochemical impedance spectroscopy (EIS) was introduced to illustrate the structural characteristics of soil-rock mixtures (SRM), aiming at deducing the relationship between physical property indices such as the mass ratio indices (e.g., water content, soil-rock ratio, and stone particle size) and volume ratio indices (e.g., porosity and saturation) and equivalent circuit at the macro and micro levels. A three-level equivalent circuit corresponding with the physical characteristic of SRM was established to describe the cementation state. It shows that the degree of cementation of SRM increases with increasing water content, rock content, and median size of block stone; meanwhile, the real impedance coefficient of the non-cemented part is lower than that of the cemented part. The corresponding relationship between the imaginary impedance and the specific gravity has segmental characteristics. The density first increases and then decreases with the increase of water content; the water content and saturation threshold are 16% and 80 ± 2%, respectively. Moreover, the saturation (Sr and n∙Sr) decreases with the increase in the real impedance coefficient. In addition, the characteristics of the propagation mode and interfacial contact characteristics of the charged material inside SRM were examined, and the macro and micro mapping of the cementation state of SRM and the basic mass transfer mode (i.e., migration, diffusion, and convection) were obtained. The mapping relationship proposed in this study reflects the micro-scale cementation characteristics and the macro-scale physical characteristics of the SRM system, which provides new insight into the multi-scale research of SRM.

Particle Swarm Optimization is a member of swarm intelligence algorithms, which is inspired by the behavior of bird flocks. The inertia weight, one of the most important parameters of PSO, is crucial for PSO, for it balances the performance of exploration and exploitation of the algorithm. This paper proposes a new inertia weight control strategy and PSO with this new strategy is tested by four benchmark functions. The results shows that the new strategy provides the PSO with better performance.

The operation schedule of an oceangoing ship is influenced by wave and wind disturbances, and is therefore weather routing. The work shows the goal of finding a safe and time-saving route by meteorological obtained based on modified genetic algorithm. By improving selection operator of genetic algorithm the author achieves the goal of finding the optimal route more quickly and precisely. In the cross operation, in order to avoid damage of the excellent gene pattern, a new cross operator has been proposed. In order to avoid local convergence of genetic algorithm, an improved mutation operator has been proposed. In the end, simulation experiments of minimum sailing time and safety routes have been conducted to illustrate the advantages of modified genetic algorithm.

A general method was proposed to study the sound and vibration of a finite cylindrical shell with elastic theory. This method was developed through comprehensive analysis of the uncoupled Helmholtz equation obtained by the decomposition of elastic equations and the structure of the solution of a finite cylindrical shell analyzed by thin shell theory. The proposed method is theoretically suitable for arbitrary thickness of the shell and any frequency. Also, the results obtained through the method can be used to determine the range of application of the thin shell theory. Furthermore, the proposed method can deal with the problems limited by the thin shell theory. Additionally, the method can be suitable for several types of complex cylindrical shell such as the ring-stiffened cylindrical shell, damped cylindrical shell, and double cylindrical shell.

Statistical properties of Rayleigh backscattering in bidirectional fiber-to-the-home passive optical networks based on on–off keying (OOK), frequency-shift keying (FSK), and differential phase-shift keying (DPSK) modulation formats have been studied. The error probability (BER) for bidirectional transmission systems using FSK or DPSK format for downstream and OOK format for upstream has been examined in the optical line terminal (OLT) and optical network unit (ONU). Also, the probability density function of the received current for the bidirectional system using OOK format for both downstream and upstream transmission is derived, and the BER has been evaluated. Our results show that the required receiver power for bidirectional system using FSK/OOK and DPSK/OOK topology in OLT is lower than that for the system using OOK/OOK topology by about 9 and 10 dB m to reach the error probability of 10 −9 for nonreturn-to-zero (NRZ) signal, respectively. In addition, we have found that using return-to-zero (RZ) modulation format can lead to significant performance improvement for OOK/OOK, FSK/OOK, and DPSK/OOK topologies at the cost of increased bandwidth.