miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

Women's empowerment and child nutrition in a context of shifting livelihoods in Eastern Oromia, Ethiopia.

Agriculture, and particularly livestock and animal source foods, has been closely linked to improvements in human nutrition. Production, income, and women's empowerment improve household food security and child nutritional outcomes in interacting ways. Khat production in Eastern Ethiopia is changing the economic and livelihood landscape for communities that have traditionally relied upon small-scale mixed agriculture and livestock production. How this shifting livelihood landscape and the empowerment of women in these communities are affecting nutritional outcomes has not been investigated. Using cross-sectional data collected during formative research for the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project, we developed models to examine the roles of livelihood activities, including livestock production, staple crop production, and khat production, and women's empowerment in child nutrition outcomes. Survey participants were randomly selected mothers of children aged 10-15 months from Haramaya district, Eastern Hararghe, Oromia, Ethiopia. Nested logistic regression models were performed for each nutrition outcome: children's animal source food consumption, children's dietary diversity, and child stunting, wasting, and underweight. Explanatory variables included those for livelihood (tropical livestock unit, crop production, and khat production ladder) and women's empowerment (as indicated by domains of the Women's Empowerment in Agriculture Index), and covariates including child sex, mother's age, mother's education, assets, income, and kebele. Results indicated that khat production and tropical livestock units were not significantly associated with any of the child nutrition outcomes. However, results did indicate that the odds of reporting child animal source food consumption in households where the mother was empowered in the leadership domain was 3.33 times that in households where the mother wasn't (p < 0.05). In addition, the odds of having a stunted child in households where the mother was empowered in the time domain was 2.68 times that in households where the mother wasn't (p < 0.05). The results from this study both support and complicate the existing literature on the associations between women's empowerment in agriculture and child nutrition outcomes, underscoring the important role that livelihood, contextual factors, and location may have on the complex relationship between empowerment domains and nutritional outcomes.

Prevalence and Load of the Campylobacter Genus in Infants and Associated Household Contacts in Rural Eastern Ethiopia: a Longitudinal Study from the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) Project.

In our previous cross-sectional study, multiple species of Campylobacter were detected (88%) in stool samples from children (12 to 14 months of age) in rural eastern Ethiopia. This study assessed the temporal fecal carriage of Campylobacter in infants and identified putative reservoirs associated with these infections in infants from the same region. The prevalence and load of Campylobacter were determined using genus-specific real-time PCR. Stool samples from 106 infants (n = 1,073) were collected monthly from birth until 376 days of age (DOA). Human stool samples (mothers and siblings), livestock feces (cattle, chickens, goats, and sheep), and environmental samples (soil and drinking water) from the 106 households were collected twice per household (n = 1,644). Campylobacter was most prevalent in livestock feces (goats, 99%; sheep, 98%; cattle, 99%; chickens, 93%), followed by human stool samples (siblings, 91%; mothers, 83%; infants, 64%) and environmental samples (soil, 58%; drinking water, 43%). The prevalence of Campylobacter in infant stool samples significantly increased with age, from 30% at 27 DOA to 89% at 360 DOA (1% increase/day in the odds of being colonized) (P < 0.001). The Campylobacter load increased linearly (P < 0.001) with age from 2.95 logs at 25 DOA to 4.13 logs at 360 DOA. Within a household, the Campylobacter load in infant stool samples was positively correlated with the load in mother stool samples (r2 = 0.18) and soil collected inside the house (r2 = 0.36), which were in turn both correlated with Campylobacter loads in chicken and cattle feces (0.60 < r2 < 0.63) (P < 0.01). In conclusion, a high proportion of infants are infected with Campylobacter in eastern Ethiopia, and contact with the mother and contaminated soil may be associated with early infections. IMPORTANCE A high Campylobacter prevalence during early childhood has been associated with environmental enteric dysfunction (EED) and stunting, especially in low-resource settings. Our previous study demonstrated that Campylobacter was frequently found (88%) in children from eastern Ethiopia; however, little is known about potential Campylobacter reservoirs and transmission pathways leading to infection of infants by Campylobacter during early growth. In the longitudinal study presented here, Campylobacter was frequently detected in infants within the 106 surveyed households from eastern Ethiopia, and the prevalence was age dependent. Furthermore, preliminary analyses highlighted the potential role of the mother, soil, and livestock in the transmission of Campylobacter to the infant. Further work will explore the species and genetic composition of Campylobacter in infants and putative reservoirs using PCR and whole-genome and metagenomic sequencing. The findings from these studies can lead to the development of interventions to minimize the risk of transmission of Campylobacter to infants and, potentially, EED and stunting.

Geographical distribution and space-time clustering of human illnesses with major Salmonella serotypes in Florida, USA, 2017-2018.

Nontyphoidal salmonellosis is the leading reported foodborne illness in Florida. Although the diversity of Salmonella serotypes circulating in Florida has been identified, the geographical characteristics of the major serotypes are poorly described. Here we examined the geospatial patterns of 803 whole-genome sequenced Salmonella isolates within seven major serotypes (Enteritidis, Newport, Javiana, Sandiego, Braenderup, Typhimurium and I 4,[5],12:i:-) with the metadata obtained from Florida Department of Health during 2017-2018. Geographically, the distribution of incidence rates varied distinctively between serotypes. Illnesses with Enteritidis and Newport serotypes were widespread in Florida. The incidence rate for Javiana was relatively higher in the north compared to the south. Typhimurium was concentrated in the northwest, while I 4,[5],12:i:-, the monophasic variant of Typhimurium was limited to the south. We also evaluated space-time clustering of isolates at the zip code level using scan statistic models. Space-time clusters were detected for each major serotype during 2017-2018. The multinomial scan statistic found the risk of illness with Javiana was higher in the north and southwest in the fall of 2017 compared to other major serotypes. This serotype-specific clustering analysis will assist in further unpacking the associations between distinct reservoirs and illnesses with major serotypes in Florida.

Unravelling the reservoirs for colonisation of infants with Campylobacter spp. in rural Ethiopia: protocol for a longitudinal study during a global pandemic and political tensions.

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for Campylobacter bacteria, which are recognised as risk factors for child malnutrition. Increasing livestock production may be beneficial for improving nutrition of children but these benefits may be negated by increased exposure to Campylobacter and research is needed to evaluate the complex pathways of Campylobacter exposure and infection applicable to low-income and middle-income countries. We aim to identify reservoirs of infection with Campylobacter spp. of infants in rural Eastern Ethiopia and evaluate interactions with child health (environmental enteric dysfunction and stunting) in the context of their sociodemographic environment. METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water and soil. These samples are analysed by a range of phenotypic and genotypic microbiological methods to characterise the genetic structure of the Campylobacter population in each of these reservoirs, which will support inference about the main sources of exposure for infants. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Florida Internal Review Board (IRB201903141), the Haramaya University Institutional Health Research Ethics Committee (COHMS/1010/3796/20) and the Ethiopia National Research Ethics Review Committee (SM/14.1/1059/20). Written informed consent is obtained from all participating households. Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals and through the Feed the Future Innovation Lab for Livestock Systems.

Integration of Biobanking Architecture with Genomics Data: Genomics Integrated Biobanking Ontology (GIBO).

Integration of clinical-pathological information of Biobanks with genomics-epidemiological data/inferences in a structured and consistent manner, mitigating inherent heterogeneities of sites/sources of data/sample collection, processing, and information storage hurdles, is primary to achieving an automated surveillance system. Genomics Integrated Biobanking Ontology (GIBO) presents a solution for preserving the contextual meaning of heterogeneous data, while interlinking different genomics and epidemiological concepts in machine comprehensible format with the biobank framework. GIBO an OWL ontology introduces 84 new classes to integrate genomics data relevant to public health.

Assessing the Need for Semantic Data Integration for Surgical Biobanks-A Knowledge Representation Perspective.

To improve patient outcomes after trauma, the need to decrypt the post-traumatic immune response has been identified. One prerequisite to drive advancement in understanding that domain is the implementation of surgical biobanks. This paper focuses on the outcomes of patients with one of two diagnoses: post-traumatic arthritis and osteomyelitis. In creating surgical biobanks, currently, many obstacles must be overcome. Roadblocks exist around scoping of data that is to be collected, and the semantic integration of these data. In this paper, the generic component model and the Semantic Web technology stack are used to solve issues related to data integration. The results are twofold: (a) a scoping analysis of data and the ontologies required to harmonize and integrate it, and (b) resolution of common data integration issues in integrating data relevant to trauma surgery.

Understanding the Gap Between Information Models and Realism-Based Ontologies Using the Generic Component Model.

The wide-spread use of Common Data Models and information models in biomedical informatics encourages assumptions that those models could provide the entirety of what is needed for knowledge representation purposes. Based on the lack of computable semantics in frequently used Common Data Models, there appears to be a gap between knowledge representation requirements and these models. In this use-case oriented approach, we explore how a system-theoretic, architecture-centric, ontology-based methodology can help to better understand this gap. We show how using the Generic Component Model helps to analyze the data management system in a way that allows accounting for data management procedures inside the system and knowledge representation of the real world at the same time.

Molecular Epidemiology of Salmonellosis in Florida, USA, 2017-2018.

The state of Florida reports a high burden of non-typhoidal Salmonella enterica with approximately two times higher than the national incidence. We retrospectively analyzed the population structure and molecular epidemiology of 1,709 clinical isolates from 2017 and 2018. We found 115 different serotypes. Rarefaction suggested that the serotype richness did not differ between children under 2 years of age and older children and adults and, there are ~22 well-characterized dominant serotypes. There were distinct differences in dominant serotypes between Florida and the USA as a whole, even though S. Enteritidis and S. Newport were the dominant serotypes in Florida and nationally. S. Javiana, S. Sandiego, and S. IV 50:z4, z23:- occurred more frequently in Florida than nationally. Legacy Multi Locus Sequence Typing (MLST) was of limited use for differentiating clinical Salmonella isolates beyond the serotype level. We utilized core genome MLST (cgMLST) hierarchical clusters (HC) to identify potential outbreaks and compared them to outbreaks detected by Pulse Field Gel Electrophoresis (PFGE) surveillance for five dominant serotypes (Enteritidis, Newport, Javiana, Typhimurium, and Bareilly). Single nucleotide polymorphism (SNP) phylogenetic-analysis of cgMLST HC at allelic distance 5 or less (HC5) corroborated PFGE detected outbreaks and generated well-segregated SNP distance-based clades for all studied serotypes. We propose "combination approach" comprising "HC5 clustering," as efficient tool to trigger Salmonella outbreak investigations, and "SNP-based analysis," for higher resolution phylogeny to confirm an outbreak. We also applied this approach to identify case clusters, more distant in time and place than traditional outbreaks but may have been infected from a common source, comparing 176 Florida clinical isolates and 1,341 non-clinical isolates across USA, of most prevalent serotype Enteritidis collected during 2017-2018. Several clusters of closely related isolates (0-4 SNP apart) within HC5 clusters were detected and some included isolates from poultry from different states in the US, spanning time periods over 1 year. Two SNP-clusters within the same HC5 cluster included isolates with the same multidrug-resistant profile from both humans and poultry, supporting the epidemiological link. These clusters likely reflect the vertical transmission of Salmonella clones from higher levels in the breeding pyramid to production flocks.

Detecting Foodborne Disease Outbreaks in Florida through Consumer Complaints.

ABSTRACT: The Florida Complaint and Outbreak Reporting System (FL-CORS) database is used by the Florida Department of Health's Food and Waterborne Disease Program as one of the tools to detect foodborne disease outbreaks (FBOs). We present a descriptive and spatial network analysis of FL-CORS data collected during 2015 to 2018. We also quantified FBOs that were investigated and confirmed because of a filed complaint and the etiological agents involved in these outbreaks. An increasing number of unique complaints filed in FL-CORS was observed during 2015 to 2018, with a sharp increase during 2017 to 2018 and a different seasonal pattern in 2018. The preferred mechanism of reporting varied by age group, with younger people more frequently filing complaints online and older people preferring reporting in person or by phone. Spatial network analysis revealed that 87% of complaints had the same county of residence and county of presumed exposure. Frequency of complaints was negatively associated with linear distance between place of residence and place of exposure at the zip code level. Counties located in North and Central Florida, as well as some coastal areas in South Florida, had higher incidence rates of complaints. Those counties tend to have a large population density, and some are popular vacation destinations. On average, 96 FBOs were reported in Florida annually, of which 60% were confirmed with successful identification of the causative agent. The 56% of the confirmed FBOs were triggered by a complaint. Throughout the years, 2.4 to 2.8 FBOs and 1.4 confirmed FBOs were identified per 100 complaints. Ciguatera toxin was the cause of 40% of all FBOs in Florida, and only 28% of outbreaks were detected through complaints. In contrast, complaints were the main source of identifying outbreaks of norovirus, nontyphoidal Salmonella enterica, and scombroid food poisoning, as well as rare outbreaks of Clostridium perfringens, Cryptosporidium spp., Shigella spp., and Vibrio vulnificus.

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome.

High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360-498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41-60%) by PCR and 88% (80-93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5-12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

Spatial Epidemiology of Salmonellosis in Florida, 2009-2018.

Non-typhoidal Salmonella enterica infections cause a high disease burden in the United States with an estimated 1.2 million illnesses annually. The state of Florida consistently has a relatively high incidence compared to other states in the United States. Nevertheless, studies regarding the epidemiology of nontyphoidal salmonellosis and its spatial and temporal patterns in Florida were rarely reported. We examined the spatial and temporal patterns of 62,947 salmonellosis cases reported to FL Health Charts between 2009 and 2018. Dominant serotypes circulating in Florida were also explored using whole genome sequencing (WGS) based serotype-prediction for 2,507 Salmonella isolates sequenced by the Florida Department of Health during 2017 and 2018. The representativeness of laboratory-sequenced isolates for reported cases was determined by regression modeling. The annual incidence rate of salmonellosis decreased from 36.0 per 100,000 population in 2009 to 27.8 per 100,000 in 2016, and gradually increased in 2017 and 2018. Increased use of culture-independent testing did not fully explain this increase. The highest incidence rate was observed in children, contributing 40.9% of total reported cases during this period. A seasonal pattern was observed with the incidence peaking in September and October, later than the national average pattern. Over these 10 years, the Northeast and Northwest regions of the state had higher reported incidence rates, while reported rates in the Southeast and South were gradually increasing over time. Serotypes were predicted based on WGS data in the EnteroBase platform. The top-five most prevalent serotypes in Florida during 2017-2018 were Enteritidis, Newport, Javiana, Sandiego and Braenderup. The highest percentage of isolates was from children under 5 years of age (41.4%), and stool (84.7%) was the major source of samples. A zero-inflated negative binomial regression model showed that the reported case number was a strong predictor for the number of lab-sequenced isolates in individual counties, and the geospatial distribution of sequenced isolates was not biased by other factors such as age group. The spatial and temporal patterns identified in this study along with the prevalence of different serotypes will be helpful for the development of efficient prevention and control strategies for salmonellosis in Florida.

Campylobacter Colonization, Environmental Enteric Dysfunction, Stunting, and Associated Risk Factors Among Young Children in Rural Ethiopia: A Cross-Sectional Study From the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) Project.

Livestock farming provides a possible mechanism by which smallholder farmers can meet their household need for animal source foods (ASF), which may reduce the risk of stunting. However, direct/indirect contacts with domestic animals may increase colonization by Campylobacter spp., which has been associated with Environmental Enteric Dysfunction (EED) and stunting. A cross-sectional study involving 102 randomly selected children between 12 and 16 months of age was conducted in rural eastern Ethiopia to establish prevalence rates of Campylobacter colonization, EED, and stunting, and evaluate potential risk factors. Data were collected between September and December 2018. The prevalence of EED and stunting was 50% (95% CI: 40-60%) and 41% (95% CI: 32-51%), respectively. Among enrolled children, 56% had consumed some ASF in the previous 24 h; 47% had diarrhea and 50% had fever in the past 15 days. 54, 63, 71 or 43% of households owned at least one chicken, cow/bull, goat, or sheep; 54 (53%) households kept chickens indoors overnight and only half of these confined the animals. Sanitation was poor, with high levels of unimproved latrines and open defecation. Most households had access to an improved source of drinking water. The prevalence of Campylobacter colonization was 50% (95% CI: 41-60%) by PCR. In addition to the thermotolerant species Campylobacter jejuni, Campylobacter coli and Campylobacter upsaliensis, non-thermotolerant species related to Campylobacter hyointestinalis and Campylobacter fetus were frequently detected by Meta-total RNA sequencing (MeTRS). Current breastfeeding and ASF consumption increased the odds of Campylobacter detection by PCR, while improved drinking water supply decreased the odds of EED. No risk factors were significantly associated with stunting. Further studies are necessary to better understand reservoirs and transmission pathways of Campylobacter spp. and their potential impact on child health.

An ANN-GA model based promoter prediction in Arabidopsis thaliana using tilling microarray data.

Identification of promoter region is an important part of gene annotation. Identification of promoters in eukaryotes is important as promoters modulate various metabolic functions and cellular stress responses. In this work, a novel approach utilizing intensity values of tilling microarray data for a model eukaryotic plant Arabidopsis thaliana, was used to specify promoter region from non-promoter region. A feed-forward back propagation neural network model supported by genetic algorithm was employed to predict the class of data with a window size of 41. A dataset comprising of 2992 data vectors representing both promoter and non-promoter regions, chosen randomly from probe intensity vectors for whole genome of Arabidopsis thaliana generated through tilling microarray technique was used. The classifier model shows prediction accuracy of 69.73% and 65.36% on training and validation sets, respectively. Further, a concept of distance based class membership was used to validate reliability of classifier, which showed promising results. The study shows the usability of micro-array probe intensities to predict the promoter regions in eukaryotic genomes.

A comparative study on the molecular descriptors for predicting drug-likeness of small molecules.

Screening of " drug-like" molecule from the molecular database produced through high throughput techniques and their large repositories requires robust classification. In our work, a set of heuristically chosen nine molecular descriptors including four from Lipinski's rule, were used as classification parameter for screening "drug-like" molecules. The robustness of classification was compared with four fundamental descriptors of Lipinski. Back propagation neural network based classifier was applied on a database of 60000 molecules for classification of, " drug-like" and "non drug-like" molecules. Classification result using nine descriptors showed high classification accuracy of 96.1% in comparison to that using four Lipinski's descriptors which yielded an accuracy of 82.48%. Also a significant decrease of false positives resulted while using nine descriptors causing a sharp 18% increase of specificity of classification. From this study it appeared that Lipinski's descriptors which mainly deal with pharmacokinetic properties of molecules form the basis for identification of "drug-like" molecules that can be substantially improved by adding more descriptors representing pharmaco-dynamics properties of molecules.

Interposition arthroplasty in post-traumatic temporomandibular joint ankylosis: A retrospective study.

Temporomandibular joint ankylosis which is most frequently caused by trauma, presents with restriction in mouth opening in early stages and if children are the victim and not treated early, it presents with growth retardation of the involved mandibular side. Various methods are available for surgical correction. We have reviewed our experience with the efficacy of different interpositional materials in post-traumatic cases in our set up with special reference to temporal fascia over last three years. Twenty seven patients with history of trauma, mostly fall from height, have been studied. They were evaluated clinically and by computed tomography (CT) scan, orthopantogram and x- ray lateral oblique view. The most common age group was 10-15 years with mean 12.5 years and male to female ratio 1:2. Preoperative mouth opening (inter incisor distance) was 1-2 mm in 17 cases and 2-4 mm in 10 cases. We have used temporalis fascia in nine, costochondral graft in seven, silastic sheets in five and T-plates in six cases. Post-operatively, adequate mouth opening of 30-50 mm was observed in six months follow-up and more than 50 mm at one year follow up in 21 cases out of which nine cases have interpositional material as temporalis fascia alone. The postoperative period was uneventful in all cases and none required re-operation for recurrences. We conclude that interpositional arthroplasty, especially with pedicled temporal fascia, is the best method to prevent recurrences and establish good mouth opening and full range of jaw movements.