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Methods for reviewing epidemiological signals are necessary to building and maintaining data-driven public health capabilities. We have developed a novel approach for assessing the plausibility of infectious disease forecasts and surveillance data. The PLANES ( PL ausibility AN alysis of E pidemiological S ignals) methodology is designed to be multi-dimensional and flexible, yielding an overall score based on individual component assessments that can be applied at various temporal and spatial granularities. Here we describe PLANES, provide a demonstration analysis, and discuss how to use the open-source rplanes R package. PLANES aims to enable modelers and public health end-users to evaluate forecast plausibility and surveillance data integrity, ultimately improving early warning systems and informing evidence-based decision-making.

The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explore the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identify a total of 1768 lncRNAs, of which 718 (~41%) are novels in P. falciparum . The subcellular localization and stage-specific expression of several putative lncRNAs are validated using RNA-FISH. Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs is explored using ChIRP. The results reveal that lncRNA occupancy sites are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis and sexual differentiation. Genomic and phenotypic analysis of one specific lncRNA demonstrate its importance in sexual differentiation and reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation, opening new avenues for targeted therapeutic strategies against the deadly malaria parasite. In eukaryotes, long non-coding RNAs (lncRNAs) are regulators of gene expression. Here the authors identify lncRNAs implicated in pathogenicity and sexual differentiation of the human malaria parasite, P. falciparum , opening novel avenues towards therapeutic strategies.

Mosquito-borne disease remains a significant burden on global health. In the United States, the major threat posed by mosquitoes is transmission of arboviruses, including West Nile virus by mosquitoes of the Culex genus. Virus metagenomic analysis of mosquito small RNA using deep sequencing and advanced bioinformatic tools enables the rapid detection of viruses and other infecting organisms, both pathogenic and non-pathogenic to humans, without any precedent knowledge. In this study, we sequenced small RNA samples from over 60 pools of Culex mosquitoes from two major areas of Southern California from 2017 to 2019 to elucidate the virome and immune responses of Culex . Our results demonstrated that small RNAs not only allowed the detection of viruses but also revealed distinct patterns of viral infection based on location, Culex species, and time. We also identified miRNAs that are most likely involved in Culex immune responses to viruses and Wolbachia bacteria, and show the utility of using small RNA to detect antiviral immune pathways including piRNAs against some pathogens. Collectively, these findings show that deep sequencing of small RNA can be used for virus discovery and surveillance. One could also conceive that such work could be accomplished in various locations across the world and over time to better understand patterns of mosquito infection and immune response to many vector-borne diseases in field samples.

Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the plus ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics in the different proliferative stages are not well understood. Genome-wide shared orthology analysis of Plasmodium spp. revealed the presence of two kinesin-8 motor proteins, kinesin-8X and kinesin-8B. Here we studied the biochemical properties of kinesin-8X and its role in parasite proliferation. In vitro, kinesin-8X has motility and depolymerization activities like other kinesin-8 motors. To understand the role of Plasmodium kinesin-8X in cell division, we used fluorescence-tagging and live cell imaging to define its location, and gene targeting to analyse its function, during all proliferative stages of the rodent malaria parasite P. berghei life cycle. The results revealed a spatio-temporal involvement of kinesin-8X in spindle dynamics and an association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the kinesin-8X gene revealed a defect in oocyst development, confirmed by ultrastructural studies, suggesting that this protein is required for oocyst development and sporogony. Transcriptome analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved mainly in microtubule-based processes, chromosome organisation and the regulation of gene expression, supporting a role for kinesin-8X in cell division. Kinesin-8X is thus required for parasite proliferation within the mosquito and for transmission to the vertebrate host.

There is consensus about the importance of developing a strong cadre of effective multilevel interventions to eliminate the impacts of unjust social processes, such as structural racism and other harmful social determinants of health (SDOH), on health inequities in the USA. However, the available cadre of rigorously evaluated evidence-based interventions for SDOH mitigation remains underdeveloped relative to the magnitude of historic and current health inequities. The proposed manuscript addresses this gap in two ways: first, by introducing a heuristic framework to inform decisions in multilevel intervention development, study design, and selection of analytic methods and, second, by providing a roadmap for future applications of the framework in multilevel intervention research through an exemplar application using the ongoing NIH-funded evaluation study of the Nurse-Community-Family Partnership (NCFP) intervention. NCFP leverages individual, family, institutional, and system factors to shape COVID-19 mitigation outcomes at the individual and household levels. NCFP takes an approach informed by the heuristic framework to addressing and mitigating unjust social processes and other harmful SDOH. We discuss the application of a two-arm parallel explanatory group randomized trial to evaluate the efficacy of NCFP in improving the primary (COVID-19 testing uptake) and secondary (adoption of COVID-19 control measures, COVID-19 vaccine uptake, mutual aid capacity, etc.) outcomes at the individual and household levels. The analysis approach relies on random-intercept models, and we calculate the variance partitioning coefficient to estimate the extent to which household- and individual-level variables contribute to the outcome, allowing examination of NCFP effects at multiple levels.

A class of small, non-coding RNAs, microRNAs (miRNAs), may play a pivotal role in the development of the neural crest (NC)- and mesoderm-derived skeleton. They are involved in a variety of biological processes that contribute to skeletal development, such as cell migration, Wnt signaling and specification of cellular fate towards osteogenesis. Identifying miRNAs involved with regulating genes that drive the two lineages that give rise to osteoblasts during development can provide distinct gene regulatory mechanisms that give rise to craniofacial deformities. Potential microRNA-to-gene target interaction (MTIs) pairs can then potentially be used as biomarkers for in utero diagnostic or treatments for skeletal deformities in the face or limbs. The aim of this study was to develop a set of miRNA biomarkers that correlate with NC and mesoderm cell differentiation into osteoblasts, and to identify miRNAs specific to these pathways. Our study was conducted in vitro using human embryonic stem cells (hESCs) that were differentiated into osteoblasts. Toxicants known to repress NC and mesoderm induction were supplied to the in vitro cultures and the RNA sequenced to obtain both small RNAs and mRNAs. To facilitate this analysis, an R Shiny web app was developed to implement the sequencing results of both microRNA and RNA. The app provides tools to separately display and visualize the results of the differential regulation of microRNAs and mRNAs. Gene ontology (GO) analysis revealed that the identified miRNA-target interactions were indeed involved in select GO pathways related to osteogenic, NC and mesoderm differentiation. The app narrowed down significantly correlated MTIs specific to each differentiation lineage. Within the NC lineage miR-30a, miR-148a and miR-195 were correlated with cadherin2 (CDH2), DNA methyltransferase 3 beta (DNMT3B) and transcription factor AP-2 alpha (TFAP2A), respectively. Within the mesoderm lineage miR-148a, miR-7 and miR-20a were correlated with DNMT3B, JARID2 and VANGL1, respectively. In the future, these miRNAs could be further validated as potential biomarkers in the context of neurocristopathies.

Purpose of Review Plaque erosion is the second leading cause of coronary thrombosis following plaque rupture and represents a key pathophysiological process underlying acute coronary syndromes that can culminate in sudden coronary death. While the precise mechanisms and risk factors driving plaque rupture are well-established, those for erosion have only recently been explored. This review summarizes current literature on the characteristics and risk factors favoring plaque erosion. Recent Findings Plaque erosion is characterized by a defective endothelial layer in the intima, promoting thrombus formation in the presence of an intact fibrous cap. It is more common in younger women (< 50 years) and smokers. Pathologic intimal thickening or fibroatheroma are common underlying lesions. Risk factors include gender, age, smoking, and disturbances in shear flow. Advances in pathogenic and molecular mechanisms, such as endothelial shear stress, neutrophil activation, and toll-like receptor-2 pathways, are discussed. Summary Understanding the major risk factors for plaque erosion can inform diagnostics and therapeutics to prevent the progression of arterial thrombosis.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021–22 and 2022–23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021–22 and 12 out of 18 models in 2022–23. Averaging across all forecast targets, the FluSight ensemble is the 2 nd most accurate model measured by WIS in 2021–22 and the 5 th most accurate in the 2022–23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change. This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

Emerging adulthood is a critical life stage when participation in higher education can facilitate the transition of young individuals into adulthood and independence. The barriers associated with low health literacy levels are higher among racial or ethnic groups facing health inequalities, including those enrolled in higher education institutions. The purpose of this basic qualitative study was to explore how health educators promoted the health literacy of Black and Latino emerging adult college students. The theoretical framework was based on Bandura’s social cognitive theory. Eight health professionals who served to promote health literacy across diverse college campuses and different states in the United States were interviewed. The interviews were coded manually to identify overarching themes from the health promotion practices and experiences noted by those engaging in college health promotion. Results showed higher education health professionals promoted health literacy by focusing on cultural awareness, using diverse strategies to engage their students, and seeking out internal and external supports to benefit their students’ health literacy levels. The results may promote social change by increasing college health professionals’ knowledge and practices to promote the health literacy of Black and Latino emerging adult college students.