Journal of Geophysical Research最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils.

Objective: To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP.

Methods: Eighty-one subjects (18-70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test.

Results: Forty-three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction.

Conclusion: In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life.

This study aimed to estimate the allelopathic intensity of four Asteraceae invasive plant species (IPS), including Conyza canadensis (L.) Cronq., Erigeron annuus (L.) Pers., Bidens pilosa (L.), and Aster subulatus Michx., by testing the effect of leaf extracts on the seed germination and seedling growth (SGe and SGr) of lettuce (Lactuca sativa L.) in combination with two particle sizes of silver nanoparticles. These four IPS decreased the germination of lettuce seeds but increased the growth of lettuce seedlings. The allelopathic intensity of the four IPS decreased in the following order: B. pilosa > C. canadensis > E. annuus > A. subulatus. Silver nanoparticles decreased the SGe and SGr of lettuce. The 20 nm silver nanoparticles affected the competition intensity for water and the absorption of inorganic salts by lettuce more intensively than the 80 nm nanoparticles. Silver nanoparticles intensify the allelopathic intensity of the four invasive plant species on the SGe and SGr of lettuce. The allelopathic intensity of B. pilosa was higher than that of the other three IPS when they were polluted with silver nanoparticles. Thus, silver nanoparticles could facilitate the invasion process of the four IPS, particularly B. pilosa, via an increase in the intensity of allelopathy.

An ongoing pandemic of newly emerged SARS-CoV-2 has puzzled many scientists and health care policymakers around the globe. The appearance of the virus was accompanied by several distinct antigenic changes, specifically spike protein which is a key element for host cell entry of virus and major target of currently developing vaccines. Some of these mutations enable the virus to attach to receptors more firmly and easily. Moreover, a growing number of trials are demonstrating higher transmissibility and, in some of them, potentially more serious forms of illness related to novel variants. Some of these lineages, especially the Beta variant of concern, were reported to diminish the neutralizing activity of monoclonal and polyclonal antibodies present in both convalescent and vaccine sera. This could imply that these independently emerged variants could make antiviral strategies prone to serious threats. The rapid changes in the mutational profile of new clades, especially escape mutations, suggest the convergent evolution of the virus due to immune pressure. Nevertheless, great international efforts have been dedicated to producing efficacious vaccines with cutting-edge technologies. Despite the partial decrease in vaccines efficacy against worrisome clades, most current vaccines are still effective at preventing mild to severe forms of disease and hospital admission or death due to coronavirus disease 2019 (COVID-19). Here, we summarize existing evidence about newly emerged variants of SARS-CoV-2 and, notably, how well vaccines work against targeting new variants and modifications of highly flexible mRNA vaccines that might be required in the future.

Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19.

Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086.

Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion.

Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits.

Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

Agency wants to retool its surveys and decennial census to improve efficiency and generate better data.

Understanding the decay and maintenance of long-term SARS-CoV-2 neutralizing antibodies in infected or vaccinated people and how vaccines protect against other SARS-CoV-2 variants is critical for assessing public vaccination plans. Here, we measured different plasm antibody levels 2 and 12 months after disease onset, including anti-RBD, anti-N, total neutralizing antibodies, and two neutralizing-antibody clusters. We found that total neutralizing antibodies declined more slowly than total anti-RBD and anti-N IgG, and the two neutralizing-antibody clusters decayed even more slowly than total neutralizing antibodies. Interestingly, the level of neutralizing antibodies at 12 months after disease onset was significantly lower than that at 2 months but more broadly neutralized SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Lambda (C.37). Significant immune escape by the Omicron variant (B.1.1.529) was also observed 2 months post-recovery. Furthermore, we revealed that a high percentage of virus-specific CD4⁺ T cells and cTfh1 were associated with a slower decline in humoral immunity, accompanied by higher levels of CXCR3 ligands such as CXCL9 and CXCL10, higher frequency of cTfh1, and lower levels of cTfh2 and cTfh17. Our data highlight the importance of coordinating T-cell and humoral immunity to achieve long-term protective immunity.

Aim: The aim of this study was to evaluate the predictability and accuracy of the Short-Form Fonseca Anamnestic Index (SFAI) in relation to the modified Helkimo Index for the diagnosis of temporomandibular disorders (TMDs).

Materials and methods: A cross-sectional, prospective, and analytical predictive study was conducted in 240 students of a public institute of higher technological education in Ica, Peru during the months of February to May 2018. The SFAI of 10 closed questions and the Helkimo Index modified by Maglione (gold standard) were used as instruments to diagnose TMDs. For the analysis of concordance between both instruments, Cohen's Kappa Index was applied. To evaluate the association according to gender and age group, Pearson's chi-square test was used. For validity of the SFAI in relation to accuracy, sensitivity and specificity were calculated, and they were verified by receiver operating characteristics (ROC) to determine the best cutoff points (area under the curve [AUC]) considering a P value < 0.05. Regarding the predictability of the SFAI, the positive and negative predictive value was calculated by applying Bayes' theorem.

Results: The SFAI was highly significantly associated with the modified Helkimo Index according to gender (P < 0.001), age group (P < 0.001), and overall (P < 0.001) moderate overall agreement (k = 0.416; 95% confidence interval [CI] = 0.287-0.545); better concordance was obtained in individuals older than 20 years (k = 0.490, CI = 0.302-0.679) and women (k = 0.565, CI = 0.371-0.759). The ROC curve analysis of the SFAI showed good accuracy (0.852, CI = 0.800-0.905) and was highly significant (P < 0.001), with an optimal cutoff point of 17.5 and good sensitivity (80.10%) and specificity (74.36%). In addition, a very good positive predictive value (PPV) (94.15%) and a fair negative predictive value (NPV) (42.02%) were obtained.

Conclusions: Although there was moderate concordance between the SFAI and the modified Helkimo Index for the diagnosis of TMDs, the SFAI obtained good accuracy in the overall analysis of sensitivity and specificity. In addition, it demonstrated a high predictive efficacy for detecting positive TMD cases, whereas its ability to rule out positive cases was fair.

Introduction: In this paper, we describe the design of a touchless peritoneal dialysis connector system and how we evaluated its potential for preventing peritoneal dialysis-associated peritonitis, in comparison to the standard of care. The unique feature of this system is an enclosure within which patients can connect and disconnect for therapy, protecting their peritoneal catheters from touch or aerosols.

Methods: We simulated a worst-case contamination scenario by spraying 40mL of a standardized inoculum [ 1×10⁷ colony-forming units (CFU) per milliliter] of test organisms, Staphylococcus epidermidis ATCC1228 and Pseudomonas aeruginosa ATCC39327, while test participants made mock connections for therapy. We then compared the incidence of fluid path contamination by test organisms in the touchless connector system and the standard of care. 4 participants were recruited to perform a total of 56 tests, divided in a 1:1 ratio between both systems. Peritoneal dialysis fluid sample from each test was collected and maintained at body temperature (37° C) for 16 hours before being plated on Luria Bertani agar, Mannitol Salts Agar and Pseudomonas isolation agar for enumeration.

Results: No contamination was observed in test samples from the touchless connector system, compared to 65%, 75% and 70% incidence contamination for the standard of care on Luria Bertani agar, Mannitol Salts Agar and Pseudomonas isolation agar respectively.

Conclusion: Results show that the touchless connector system can prevent fluid path contamination even in heavy bacterial exposures and may help reduce peritoneal dialysis-associated peritonitis risks from inadvertent contamination with further development.

Objective: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics.

Methods: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis.

Results: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer.

Conclusion: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Hematopoietic stem cells (HSCs) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance, which is essential for the homeostasis of hematopoietic system. Dysregulation of quiescence causes HSC dysfunction and may result in aberrant hematopoiesis (e.g., myelodysplastic syndrome and bone marrow failure syndromes) and leukemia transformation. Accumulating evidence indicates that both intrinsic molecular networks and extrinsic signals regulate HSC quiescence, including cell-cycle regulators, transcription factors, epigenetic factors, and niche factors. Further, the transition between quiescence and activation of HSCs is a continuous developmental path driven by cell metabolism (e.g., protein synthesis, glycolysis, oxidative phosphorylation, and autophagy). Elucidating the complex regulatory networks of HSC quiescence will expand the knowledge of HSC hemostasis and benefit for clinical HSC use. Here, we review the current understanding and progression on the molecular and metabolic regulation of HSC quiescence, providing a more complete picture regarding the mechanisms of HSC quiescence maintenance.