Background. Concerns remain about lower effectiveness waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both ...the monovalent (RV1; 2-does series) and pentavalent (RV5; 3-does series) vaccines were introduced in 2010. Methods. A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth data and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness (1 – odds ratio of vaccination × 100%) was computed using logistic regression models. Results. We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2–3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval CI, 58%–84%) with hospital controls, and 52% (95% CI, 26%–69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6–11 months (74% 95% CI, 18%–92%) and children ≥12 months of age (71% 95% CI, 44%–85%) (P = .85), nor between complete courses of RV1 (63% 95% CI, 23%–82%) and RV5 (69% 95% CI, 29%−87%) (P = .96). An uncommon G12P8 strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. Conclusions. RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur.
Q-fever is a flu-like illness caused by Coxiella burnetii (Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune ...protection to Cb infection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control of Cb infection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response to Cb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response to Cb vaccine and challenge, which can inform the assessment of candidate vaccines for Cb.
We investigated the sensitivity of regional tumor response prediction to variability in voxel clustering techniques, imaging features, and machine learning algorithms in 25 patients with locally ...advanced non-small cell lung cancer (LA-NSCLC) enrolled on the FLARE-RT clinical trial. Metabolic tumor volumes (MTV) from pre-chemoradiation (PETpre) and mid-chemoradiation fluorodeoxyglucose-positron emission tomography (FDG PET) images (PETmid) were subdivided into K-means or hierarchical voxel clusters by standardized uptake values (SUV) and 3D-positions. MTV cluster separability was evaluated by CH index, and morphologic changes were captured by Dice similarity and centroid Euclidean distance. PETpre conventional features included SUVmean, MTV/MTV cluster size, and mean radiation dose. PETpre radiomics consisted of 41 intensity histogram and 3D texture features (PET Oncology Radiomics Test Suite) extracted from MTV or MTV clusters. Machine learning models (multiple linear regression, support vector regression, logistic regression, support vector machines) of conventional features or radiomic features were constructed to predict PETmid response. Leave-one-out-cross-validated root-mean-squared-error (RMSE) for continuous response regression (ΔSUVmean) and area-under-receiver-operating-characteristic-curve (AUC) for binary response classification were calculated. K-means MTV 2-clusters (MTVhi, MTVlo) achieved maximum CH index separability (Friedman p < 0.001). Between PETpre and PETmid, MTV cluster pairs overlapped (Dice 0.70-0.87) and migrated 0.6-1.1 cm. PETmid ΔSUVmean response prediction was superior in MTV and MTVlo (RMSE = 0.17-0.21) compared to MTVhi (RMSE = 0.42-0.52, Friedman p < 0.001). PETmid ΔSUVmean response class prediction performance trended higher in MTVlo (AUC = 0.83-0.88) compared to MTVhi (AUC = 0.44-0.58, Friedman p = 0.052). Models were more sensitive to MTV/MTV cluster regions (Friedman p = 0.026) than feature sets/algorithms (Wilcoxon signed-rank p = 0.36). Top-ranked radiomic features included GLZSM-LZHGE (large-zone-high-SUV), GTSDM-CP (cluster-prominence), GTSDM-CS (cluster-shade) and NGTDM-CNT (contrast). Top-ranked features were consistent between MTVhi and MTVlo cluster pairs but varied between MTVhi-MTVlo clusters, reflecting distinct regional radiomic phenotypes. Variability in tumor voxel cluster response prediction can inform robust radiomic target definition for risk-adaptive chemoradiation in patients with LA-NSCLC. FLARE-RT trial: NCT02773238.
The recent emergence of the mosquito-borne Zika virus (ZIKV) in the Americas has become a global public health concern. We describe a series of experimental infections designed to investigate whether ...animals within certain taxonomic groups in North America have the potential to serve as ZIKV amplifying or maintenance hosts. Species investigated included armadillos, cottontail rabbits, goats, mink, chickens, pigeons, ground hogs, deer mice, cattle, raccoons, ducks, Syrian Golden hamsters, garter snakes, leopard frogs, house sparrows, and pigs. Infectious virus was isolated from blood only in frogs and armadillos; however, the magnitude of viremia was low. In addition, neutralizing antibodies were detected after infection in goats, rabbits, ducks, frogs, and pigs. This study indicates that the animals tested to date are unlikely to act as animal reservoirs for ZIKV, but that rabbits and pigs could potentially serve as sentinel species. Understanding the transmission cycle and maintenance of ZIKV in animals will help in developing effective surveillance programs and preventative measures for future outbreaks.
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•Evolutionary consequences of hybridization in a coral reef fish complex.•Genetic analyses of 645 individuals from four species of surgeonfish sampled across the Indo-Pacific.•Recent ...separation between all species of 235,000–2.25million years.•Hybridization between all species at suture zones due to secondary contact.•Introgression levels vary among species producing different evolutionary outcomes.
Closely related species can provide valuable insights into evolutionary processes through comparison of their ecology, geographic distribution and the history recorded in their genomes. In the Indo-Pacific, many reef fishes are divided into sister species that come into secondary contact at biogeographic borders, most prominently where Indian Ocean and Pacific Ocean faunas meet. It is unclear whether hybridization in this contact zone represents incomplete speciation, secondary contact, an evolutionary dead-end (for hybrids) or some combination of the above. To address these issues, we conducted comprehensive surveys of two widely-distributed surgeonfish species, Acanthurus leucosternon (N=141) and A. nigricans (N=412), with mtDNA cytochrome b sequences and ten microsatellite loci. These surgeonfishes are found primarily in the Indian and Pacific Oceans, respectively, but overlap at the Christmas and Cocos-Keeling Islands hybrid zone in the eastern Indian Ocean. We also sampled the two other Pacific members of this species complex, A. achilles (N=54) and A. japonicus (N=49), which are known to hybridize with A. nigricans where their ranges overlap. Our results indicate separation between the four species that range from the recent Pleistocene to late Pliocene (235,000–2.25million years ago). The Pacific A. achilles is the most divergent (and possibly ancestral) species with mtDNA dcorr≈0.04, whereas the other two Pacific species (A. japonicus and A. nigricans) are distinguishable only at a population or subspecies level (ΦST=0.6533, P<0.001). Little population structure was observed within species, with evidence of recent population expansion across all four geographic ranges. We detected sharing of mtDNA haplotypes between species and extensive hybridization based on microsatellites, consistent with later generation hybrids but also the effects of allele homoplasy. Despite extensive introgression, 98% of specimens had concordance between mtDNA lineage and species identification based on external morphology, indicating that species integrity may not be eroding. The A. nigricans complex demonstrates a range of outcomes from incomplete speciation to secondary contact to decreasing hybridization with increasing evolutionary depth.
Abstract
Lignocellulosic biomass is composed of three major biopolymers: cellulose, hemicellulose and lignin. Analytical tools capable of quickly detecting both glycan and lignin deconstruction are ...needed to support the development and characterization of efficient enzymes/enzyme cocktails. Previously we have described nanostructure-initiator mass spectrometry-based assays for the analysis of glycosyl hydrolase and most recently an assay for lignin modifying enzymes. Here we integrate these two assays into a single multiplexed assay against both classes of enzymes and use it to characterize crude commercial enzyme mixtures. Application of our multiplexed platform based on nanostructure-initiator mass spectrometry enabled us to characterize crude mixtures of laccase enzymes from fungi
Agaricus bisporus
(
Ab
) and
Myceliopthora thermophila
(
Mt
) revealing activity on both carbohydrate and aromatic substrates. Using time-series analysis we determined that crude laccase from
Ab
has the higher GH activity and that laccase from
Mt
has the higher activity against our lignin model compound. Inhibitor studies showed a significant reduction in Mt GH activity under low oxygen conditions and increased activities in the presence of vanillin (common GH inhibitor). Ultimately, this assay can help to discover mixtures of enzymes that could be incorporated into biomass pretreatments to deconstruct diverse components of lignocellulosic biomass.
A novel reticular node in the brainstem synchronizes neonatal mouse crying with breathing Highlights d Speech is a stereotyped rhythmic behavior predicted to be driven by a CPG d Similar to speech, ...mouse cries have rhythmic syllables and a stereotyped motor program d The iRO has the connectivity and intrinsic rhythmicity to produce timed cries d The iRO is necessary and sufficient for cries and the embedded syllable structure
In the modern era, patients often resort to the internet for answers to their health-related concerns, and clinics face challenges to providing timely response to patient concerns. This has led to a ...need to investigate the capabilities of AI chatbots for ophthalmic diagnosis and triage. In this in silico study, 80 simulated patient complaints in ophthalmology with varying urgency levels and clinical descriptors were entered into both ChatGPT and Bard in a systematic 3-step submission process asking chatbots to triage, diagnose, and evaluate urgency. Three ophthalmologists graded chatbot responses. Chatbots were significantly better at ophthalmic triage than diagnosis (90.0% appropriate triage vs. 48.8% correct leading diagnosis;
< 0.001), and GPT-4 performed better than Bard for appropriate triage recommendations (96.3% vs. 83.8%;
= 0.008), grader satisfaction for patient use (81.3% vs. 55.0%;
< 0.001), and lower potential harm rates (6.3% vs. 20.0%;
= 0.010). More descriptors improved the accuracy of diagnosis for both GPT-4 and Bard. These results indicate that chatbots may not need to recognize the correct diagnosis to provide appropriate ophthalmic triage, and there is a potential utility of these tools in aiding patients or triage staff; however, they are not a replacement for professional ophthalmic evaluation or advice.
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