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Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.

Strongyloides stercoralis is an intestinal parasitic nematode that causes hyperinfection and/or a dissemination syndrome in hosts, which is often difficult to diagnose. This study aims to compare the diagnostic efficacy of four conventional methods used to diagnose strongyloidiasis with real-time polymerase chain reaction (qPCR) to detect S. stercoralis in fecal samples. We analyzed 143 fecal samples collected from Colombian regions with varying degrees of risk for intestinal infections caused by S. stercoralis to assess the validity, performance, overall efficiency, and concordance of the qPCR using a direct stool test, modified Ritchie concentration technique, agar plate culture, and Harada-Mori technique as reference tests. While four fecal samples were positive for S. stercoralis using conventional methods, 32 were positive via qPCR. The diagnostic sensitivity of the qPCR was 75% [95% confidence interval (CI): 20.07-100%], whereas its specificity, negative predictive value, negative likelihood ratio, and Youden's J index were 78.42% (95% CI: 71.22-85.62%), 99.09% (95% CI: 96.86-100%), 0.32 (95% CI: 0.06-1.74), and 0.53, respectively. In addition, the estimated kappa index between the qPCR and the conventional methods was 0.12 (95% CI: -0.020-0.26). The diagnostic sensitivity of qPCR to detect strongyloidiasis is analogous to that of conventional parasitology methods, with an additional advantage of being capable of identifying the parasite DNA at low sample concentrations.

Introducción: Las parasitosis intestinales humanas se consideran un grave problema de salud pública en países de bajos ingresos; ellas además presentan nexos clínicos y epidemiológicos con la anemia y la desnutrición, especialmente en comunidades indígenas. Objetivo: Determinar la prevalencia de parasitosis intestinal, anemia y desnutrición en niños de un resguardo indígena Nasa de Caldono, en el Departamento del Cauca, y su distribución según variables clínicas, sociodemográficas y de infraestructura sanitaria. Métodos: Estudio transversal con fuente de información primaria. La muestra de estudio estuvo formada por 62 niños a quienes se les hicieron evaluación parasitológica en materia fecal, mediciones antropométricas para evaluar el estado nutricional y determinar la prevalencia de diferentes tipos de desnutrición, medición de hemoglobina para establecer la anemia. La descripción del grupo se realizó con medidas de resumen para la edad y frecuencias para las demás variables, se calculó la prevalencia de los tres eventos (parasitosis, desnutrición, anemia) y se exploró su asociación con variables independientes mediante pruebas de hipótesis. Se usó el programa SPSS 22.0. Resultados: Se encontró una prevalencia de parasitosis intestinal de 95,2%, anemia de 21,0% y desnutrición crónica de 35,5%. A pesar de no hallar asociación estadística con las condiciones sociodemográficas y sanitarias, se encontró elevada frecuencia de factores de riesgo para los tres eventos como la baja escolaridad de los padres, baja disponibilidad de acueducto y alcantarillado, así como una elevada morbilidad sentida. Conclusión: La comunidad indígena evaluada presentó altas prevalencias de parasitosis intestinal, anemia y desnutrición, lo que representa implicaciones prácticas para la orientación de los programas de salud indígena; la exploración de asociaciones requiere estudios con mayor tamaño de muestra que garantice una mayor potencia estadística.

BackgroundUnderstanding mechanisms of immune evasion to therapeutics or during responses to cancer, autoimmunity and infectious diseases requires high-dimensional functional profiling at the single-cell level. Measurement of functional immune cell signatures that include both inflammation and immunosuppression provides key insights into several facets of cancer research and therapy. If single-cell detection of cytokines spanning many cell lineages was possible, 1) determining mechanisms underlying success/failure of checkpoint blockade, 2) defining immunosuppressive activity of the tumor-resident cell subsets and 3) identifying immunological biomarkers that predict clinical outcomes would be within reach. Based on previous demonstration of superior signal resolution for intracellular readouts when compared with fluorescent cytometry, we used CyTOF™ technology to achieve this goal of high-parameter cross-functional profiling. Through the application of this orthogonal technology, we circumvent the limitations of fluorescence-based cytometry, such as signal spillover, autofluorescence, compensation errors and spectral unmixing complications.MethodsA 50-marker CyTOF panel that achieves comprehensive phenotyping of immune subpopulations with detection of 20-plus intracellular cytokines spanning Th1, Th2, Th17 and Treg lineages for functional profiling was developed. PBMC were cultured with an array of stimulation conditions, stained and acquired on the CyTOF XT system. Datasets were analyzed using PhenoGraph clustering and visualized with opt-SNE to determine cellular functional diversity.ResultsOur findings show clear detection of IL-5-, IL-10- and IL-13-producing cells, found in surprising co-expression patterns with pro-inflammatory cytokines such as IFNγ. More significantly, we were able to detect expression of several secretory analytes that are historically difficult to identify by flow cytometry at a single-cell level, including the immunosuppressive cytokine TGF-β. Furthermore, deeper analyses of functional immune capacity unveiled unique, previously unidentified subpopulations of potential interest.ConclusionsMass cytometry, in concert with this comprehensive cytokine profiling panel, provides a far wider lens of visualization of the functional diversity of human immune cells than has been achieved previously. We predict that using this panel, novel immune regulatory mechanisms that abate/prevent cellular responses in tumors will be revealed. Furthermore, given the ease of panel design and customization offered by mass cytometry, this panel provides a scaffold for easily constructing additional panels to address research-specific needs. In sum, our findings indicate that the CyTOF XT platform is well positioned as a catalyst for seminal discoveries in immune profiling to drive therapeutic design and advanced disease monitoring in cancer.For Research Use Only. Not for use in diagnostic procedures.

Off the shelf CD4+ T cell therapies, particularly those with immunoregulatory or cell repair functions, could be transformative in CAR therapies for cancers and treatment of chronic inflammatory diseases. However, progress is stunted in this area due to challenges generating human CD4+ T cells from induced pluripotent stem cells. Here we describe a key role for the withdrawal of Notch ligand during the final step of stimulation through the T cell receptor to prompt T cell maturation allowing access to the CD4 lineage in iPSC T cells (iCD4+ T cells). Functional analyses of iCD4+ T cells using a novel high-parameter CyTOF intracellular cytokine staining panel revealed both canonical Th1 cytokine signatures and cells producing varying combinations of other cytokines including IL-4, IL-8, and IL-13. Single cell RNA sequencing of iCD4+ T cells demonstrated a transcriptional signature similar to human blood CD4+ T cells. We believe this robust yet simple platform represents a key step towards the generation of off the shelf iCD4+ T cell therapies with utility for the treatment of a panoply of diseases including cancer and inflammatory autoimmune disorders. T cell receptor stimulation of iPSC CD4+/CD8+ T cell progenitors on coating without Notch ligand allows access to the CD4+ T cell lineage iPSC derived CD4+ T cells express varied cytokines in response to stimulation

Unraveling biological complexity, whether it be immune subset distribution in infectious disease(s), autoimmunity or tumor heterogeneity, requires technologies capable of single-cell proteomic analysis, such as flow cytometry. Surface immunophenotyping alone is often insufficient, as interrogating functional capacity is required to determine cellular mechanisms and effectively inform diagnostic biomarker discovery, therapeutics and vaccine development. However, large panels with intracellular markers are subject to numerous challenges, including spectral overlap and background cellular autofluorescence, reducing resolving power for rare subsets or populations defined by low-abundance expression. We posited that mass cytometry may overcome such limitations; to address this, 3 small (11 or 12-plex) clone-matched antibody panels were evaluated by spectral flow and mass cytometry. Panels were comprised of surface and intracellular targets (phospho-epitopes, transcription factors or cytokines) and designed to minimize fluorescence spectral overlap. CyTOF technology offered superior signal resolution across the range of intracellular targets. Improved signal-to-noise provided better resolution of phospho-events and transcription factor expression, in particular TOX and T-bet. Most strikingly, stimulation-specific IL-10+ and IL-13+ cells were only detected by CyTOF. Superior resolution of these cytokines enabled accurate population clustering, permitting more unique immune cell signatures to be found, including Tr1 and Tc2 populations, thus providing a more comprehensive picture of the immuno-diversity present. Our findings indicate that CyTOF technology could catalyze seminal discoveries in functional immune profiling, driving therapeutic design and diagnostics.

Watermelon [Citrullus lanatus (Thunb) Matsun & Nakai] vine decline has caused great economic losses in the southwestern region of Puerto Rico. During 2007 and 2008 fields trials were conducted at the Agricultural Experiment Station at Juana Díaz, Puerto Rico, to determine watermelon susceptibility and vectors role in the disease. In a randomized complete block design with four replicates, cultivar Royal Sweet was planted with application of insecticides were compared with UV reflective plastic mulch treatment and an untreated control. The treatment with insecticide and fungicide increased yield in a 40% when compared to the control. Cultivars Royal Sweet, Starbright, Sangría, Regency XR-212 were planted with no application of insecticides or fungicides. The disease was present and because of the severity of the disease there was no commercial production of fruit. Serological tests identified mixed infections of the same viruses. The most important vector was whitefly, Bemisia tabaci. Aphis gossypii. Weed species infected with potyvirus were: Momordica charantia, Cuccumis anguria, C. dipsaceus, Cissus verticellata, Ipomea ochracea, I. trifolia and Merremia umbellate. The disease was transmitted by mechanic inoculation to healthy plants and were positive for a potyvirus different from ZYMV and PRSV. This was corroborated with RT-PCR and PCR.

This paper develops an actionable interdisciplinary model that quantifies and assesses uncertainties in water resource allocation under climate change. To achieve this objective, we develop an innovative socio-ecological grand ensemble that combines climate, hydrological, and microeconomic ensemble experiments with a widely used decision support system for water resource planning and management. Each system is populated with multiple models (multi-model), which we use to evaluate the impacts of multiple climate scenarios and policies (multi-scenario, multi-forcing) across systems so as to identify plausible futures where water management policies meet or miss their objectives and to explore potential tipping points. The application of the methods is exemplified by a study conducted in the Douro River basin (DRB), an agricultural basin located in central Spain. Our results show how marginal climate changes can trigger non-linear water allocation changes in the decision support systems (DSSs) and/or non-linear adaptive responses of irrigators to water shortages. For example, while some irrigators barely experience economic losses (average profit and employment fall by < 0.5 %) under mild water allocation reductions of 5 % or lower, profit and employment fall by up to 12 % (∼ 24 ×) when water allocation is reduced by 10 % or less (∼ 2×). This substantiates the relevance of informing the potential natural and socio-economic impacts of adaptation strategies and related uncertainties for identifying robust decisions.

Inhibitory regulation of the heart is determined by both cholinergic M 2 receptors (M 2 R) and adenosine A 1 receptors (A 1 R) that activate the same signaling pathway, the ACh-gated inward rectifier K + (K ACh ) channels via G i/o proteins. Previously, we have shown that the agonist-specific voltage sensitivity of M 2 R underlies several voltage-dependent features of I KACh , including the ‘relaxation’ property, which is characterized by a gradual increase or decrease of the current when cardiomyocytes are stepped to hyperpolarized or depolarized voltages, respectively. However, it is unknown whether membrane potential also affects A 1 R and how this could impact I KACh . Upon recording whole-cell currents of guinea-pig cardiomyocytes, we found that stimulation of the A 1 R-G i/o - I KACh pathway with adenosine only caused a very slight voltage dependence in concentration-response relationships (~1.2-fold EC 50 increase with depolarization) that was not manifested in the relative affinity, as estimated by the current deactivation kinetics (τ = 4074 ± 214 ms at -100 mV and τ = 4331 ± 341 ms at +30 mV; P = 0.31). Moreover, I KACh did not exhibit relaxation. Contrarily, activation of the M 2 R-G i/o - I KACh pathway with acetylcholine induced the typical relaxation of the current, which correlated with the clear voltage-dependent effect observed in the concentration-response curves (~2.8-fold EC 50 increase with depolarization) and in the I KACh deactivation kinetics (τ = 1762 ± 119 ms at -100 mV and τ = 1503 ± 160 ms at +30 mV; P = 0.01). Our findings further substantiate the hypothesis of the agonist-specific voltage dependence of GPCRs and that the I KACh relaxation is consequence of this property.