Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after ...SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration.
A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population.
A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11–3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33–0.92).
Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.
Purpose
To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC).
Methods
We ...analysed AEEC cross‐sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population‐based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL.
Results
Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was −0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11–1.24), more total near work (OR = 1.05; 95% CI, 1.02–1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75–0.88) were associated with myopia (p’s < 0.05). These factors were similarly associated with SE and AL (p’s < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83).
Conclusion
In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.
Several kinase fusions are established targetable drivers in lung cancers. However, rapid and comprehensive detection remains challenging because of diverse partner genes and breakpoints. We assess ...the clinical utility and performance of a rapid microfluidic multiplex real-time PCR–based assay for simultaneous query of fusions involving ALK, ROS1, RET, and NTRK1/2/3, as well as MET exon 14 skipping, using a 3-hour automated process. Dual analytic strategies were utilized: fusion-specific amplification and 3′ to 5′ expression imbalance. One-hundred and forty-three independent, formalin-fixed, paraffin-embedded tumor samples (112 surgical specimens, 31 cytologic cell blocks) were analyzed: 133 with known kinase gene alterations and 10 negative samples based on clinically validated next-generation sequencing. Testing was successful in 142 (99%) cases. The assay demonstrated a sensitivity of 97% (28/29), 100% (31/31), 92% (22/24), 81% (22/27), and 100% (20/20) for ALK, RET, ROS1, and NTRK1/2/3 rearrangements and MET exon 14 skipping alterations, respectively, with 100% specificity for all. Concordant results were achieved in specimens aged up to 5 years, with >10% tumor, and inputs of at least 9 mm2 (surgical specimens) and 9000 cells (cytologic cell blocks). The assay enables rapid screening for clinically actionable kinase alterations with quicker turnaround and lower tissue requirements compared with immunohistochemistry and molecular methods, while also circumventing the infrastructure dependencies associated with next-generation sequencing and fluorescence in situ hybridization.
Abstract
Background
Drug regimens that include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in tuberculous meningitis (TBM). Safety data on their use ...in combination and in the context of human immunodeficiency virus (HIV) are needed to inform clinical trial design.
Methods
We conducted a phase 2, open-label, parallel-design, randomized, controlled trial to assess the safety of high-dose rifampicin, linezolid, and high-dose aspirin in HIV-associated TBM. Participants were randomized (1.4:1:1) to 3 treatment arms (1, standard of care SOC; 2, SOC + additional rifampicin up to 35 mg/kg/d + linezolid 1200 mg/d reducing after 28 days to 600 mg/d; 3, as per arm 2 + aspirin 1000 mg/d) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed.
Results
A total of 52 participants with HIV-associated TBM were randomized; 59% had mild disease (British Medical Research Council (MRC) grade 1) vs 39% (grade 2) vs 2% (grade 3). AESI or death occurred in 10 of 16 (63%; arm 3) vs 4 of 14 (29%; arm 2) vs 6 of 20 (30%; arm 1; P = .083). The cumulative proportion of AESI or death (Kaplan–Meier) demonstrated worse outcomes in arm 3 vs arm 1 (P = .04); however, only 1 event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) between arms.
Conclusions
High-dose rifampicin and adjunctive linezolid can safely be added to the standard of care in HIV-associated TBM. Larger studies are required to determine whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit.
Clinical Trials Registration
NCT03927313.
In this phase 2A, randomized, controlled trial, we demonstrate that high-dose rifampicin and adjunctive linezolid is safe in adult human immunodeficiency virus–associated tuberculous meningitis. Larger studies are required to evaluate potential toxicity with high-dose aspirin in relation to benefit on morbidity and mortality.
Squamous cell carcinoma (SCC) is uncommon in African Americans (AAs), with an incidence of approximately 0.003%. However, it is the most common skin cancer in that patient population. In AAs, SCC ...typically arises in sun-protected areas and mainly affects patients older than 50 years. We report a case of giant SCC in an AA man in his 40s with long-standing folliculitis decalvans on the scalp. Three previous skin biopsies were inconclusive. A wide excision was performed and the defect was reconstructed with an anterolateral thigh free flap. Histological analysis of the resected specimen revealed a well-moderately differentiated keratinising SCC with clear cell changes, severe mixed inflammation, folliculitis and dermal scar. He was discharged 2 weeks later and has been followed up closely. Four months later, the patient presents with metastatic SCC to an occipital lymph node.
New cyanobacteria-derived bifunctional analogues of doscadenamide A, a LasR-dependent quorum sensing (QS) activator in Pseudomonas aeruginosa, characterized by dual acylation of the pyrrolinone core ...structure and the pendant side chain primary amine to form an imide/amide hybrid are reported. The identities of doscadenamides B–J were confirmed through total synthesis and a strategic focused library with different acylation and unsaturation patterns was created. Key molecular interactions for binding with LasR and a functional response through mutation studies coupled with molecular docking were identified. The structure–activity relationships (SARs) were probed in various Gram-negative bacteria, including P. aeruginosa and Vibrio harveyi, indicating that the pyrrolinone-N acyl chain is critical for full agonist activity, while the other acyl chain is dispensable or can result in antagonist activity, depending on the bacterial system. Since homoserine lactone (HSL) quorum sensing activators have been shown to act in synergy with TRAIL to induce apoptosis in cancer cells, selected doscadenamides were tested in orthogonal eukaryotic screening systems. The most potent QS agonists, doscadenamides S10–S12, along with doscadenamides F and S4 with partial or complete saturation of the acyl side chains, exhibited the most pronounced synergistic effects with TRAIL in triple negative MDA-MB-231 breast cancer cells. The overall correlation of the SAR with respect to prokaryotic and eukaryotic targets may hint at coevolutionary processes and intriguing host–bacteria relationships. The doscadenamide scaffold represents a non-HSL template for combination therapy with TRAIL pathway stimulators.
Induction of an antibody response capable of recognizing highly diverse strains is a major obstacle to the development of vaccines for viruses such as HIV and influenza. Here, we report the dynamics ...of B cell expansion and evolution at the single-cell level after vaccination with a replication-competent adenovirus type 4 recombinant virus expressing influenza H5 hemagglutinin. Fluorescent H1 or H5 probes were used to quantitate and isolate peripheral blood B cells and their antigen receptors. We observed increases in H5-specific antibody somatic hypermutation and potency for several months beyond the period of active viral replication that was not detectable at the serum level. Individual broad and potent antibodies could be isolated, including one stem-specific antibody that is part of a new multidonor class. These results demonstrate prolonged evolution of the B cell response for months after vaccination and should be considered in efforts to evaluate or boost vaccine-induced immunity.
A phylogeny of the fungal phylum Basidiomycota is presented based on a survey of 160 taxa and five nuclear genes. Two genes,
rpb2, and
tef1, are presented in detail. The
rpb2 gene is more variable ...than
tef1 and recovers well-supported clades at shallow and deep taxonomic levels. The
tef1 gene recovers some deep and ordinal-level relationships but with greater branch support from nucleotides compared to amino acids. Intron placement is dynamic in
tef1, often lineage-specific, and diagnostic for many clades. Introns are fewer in
rpb2 and tend to be highly conserved by position. When both protein-coding loci are combined with sequences of nuclear ribosomal RNA genes, 18 inclusive clades of Basidiomycota are strongly supported by Bayesian posterior probabilities and 16 by parsimony bootstrapping. These numbers are greater than produced by single genes and combined ribosomal RNA gene regions. Combination of nrDNA with amino acid sequences, or exons with third codon positions removed, produces strong measures of support, particularly for deep internodes of Basidiomycota, which have been difficult to resolve with confidence using nrDNA data alone. This study produces strong boostrap support and significant posterior probabilities for the first time for the following monophyletic groups: (1) Ustilaginomycetes plus Hymenomycetes, (2) an inclusive cluster of hymenochaetoid, corticioid, polyporoid, Thelephorales, russuloid, athelioid, Boletales, and euagarics clades, (3) Thelephorales plus the polyporoid clade, (4) the polyporoid clade, and (5) the cantharelloid clade. Strong support is also recovered for the basal position of the Dacrymycetales in the Hymenomycetidae and paraphyly of the Exobasidiomycetidae.
We sought to develop and validate age-specific instruments for measuring early childhood resilience at ages 3, 5 and 8 in the Taiwan Birth Cohort Study, a national longitudinal study.
Using data from ...18,553 mother-infant pairs, we conducted exploratory factor analysis (EFA) on a simple random half of our sample. We then used the remaining half of these data for confirmatory factor analysis (CFA) to further assess the fit of 3 CFA models (ie, first-order, second-order, and bifactor). Psychometric properties, distributions, and inter-item and inter-factor correlations of each instrument were also evaluated.
EFA and CFA showed that the bifactor model of resilience (which included a general resilience factor and 5 specific factors) had the best fit for all 3 resilience scales, with 19 items at year 3, 18 items at year 5, and 19 items at year 8. All 3 resilience scales showed good psychometric properties, including construct validity, internal consistency, and normal distributions. For predictive validity, we found that in the face of adversity (measured by the High Risk Family Score), individuals with high resilience scores at age 3 had better general health scores at ages 3, 5, and 8 compared to those with low resilience scores.
We describe the development and validation of age-appropriate survey instruments to assess resilience in young children at the population level. These instruments can be used to better understand how resilience can impact child health over time, and to identify key factors that can foster resilience.
