The efficacy of whole human genome capture on ancient dental calculus and dentin

Objectives: Dental calculus is among the richest known sources of ancient DNA in the archaeological record. Although most DNA within calculus is microbial, it has been shown to contain sufficient human DNA for the targeted retrieval of whole mitochondrial genomes. Here, we explore whether calculus is also a viable substrate for whole human genome recovery using targeted enrichment techniques. Materials and methods: Total DNA extracted from 24 paired archaeological human dentin and calculus samples was subjected to whole human genome enrichment using in-solution hybridization capture and high-throughput sequencing. Results: Total DNA from calculus exceeded that of dentin in all cases, and although the proportion of human DNA was generally lower in calculus, the absolute human DNA content of calculus and dentin was not significantly different. Whole genome enrichment resulted in up to fourfold enrichment of the human endogenous DNA content for both dentin and dental calculus libraries, albeit with some loss in complexity. Recovering more on-target reads for the same sequencing effort generally improved the quality of downstream analyses, such as sex and ancestry estimation. For nonhuman DNA, comparison of phylum-level microbial community structure revealed few differences between precapture and postcapture libraries, indicating that off-target sequences in human genome-enriched calculus libraries may still be useful for oral microbiome reconstruction. Discussion: While ancient human dental calculus does contain endogenous human DNA sequences, their relative proportion is low when compared with other skeletal tissues. Whole genome enrichment can help increase the proportion of recovered human reads, but in this instance enrichment efficiency was relatively low when compared with other forms of capture. We conclude that further optimization is necessary before the method can be routinely applied to archaeological samples

Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification.

To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli 341-534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non-targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon sequencing. Through comparisons of microbial taxonomic counts from paired amplicon (V3 U341F/534R) and shotgun sequencing datasets, we demonstrate that extensive length polymorphisms in the V3 region are a consistent and major cause of differential amplification leading to taxonomic bias in ancient microbiome reconstructions based on amplicon sequencing. We conclude that systematic amplification bias confounds attempts to accurately reconstruct microbiome taxonomic profiles from 16S rRNA V3 amplicon data generated using universal primers. Because in silico analysis indicates that alternative 16S rRNA hypervariable regions will present similar challenges, we advocate for the use of a shotgun metagenomics approach in ancient microbiome reconstructions

Ancient dental calculus preserves signatures of biofilm succession and interindividual variation independent of dental pathology

Dental calculus preserves oral microbes, enabling comparative studies of the oral microbiome and health through time. However, small sample sizes and limited dental health metadata have hindered health-focused investigations to date. Here, we investigate the relationship between tobacco pipe smoking and dental calculus microbiomes. Dental calculus from 75 individuals fromthe 19th century Middenbeemster skeletal collection (Netherlands) were analyzed by metagenomics. Demographic and dental health parameters were systematically recorded, including the presence/number of pipe notches. Comparative data sets fromEuropean populations before and after the introduction of tobaccowere also analyzed. Calculus species profileswere comparedwith oral pathology to examine associations between microbiome community, smoking behavior, and oral health status. The Middenbeemster individuals exhibited relatively poor oral health,with a high prevalence of periodontal disease, caries, heavy calculus deposits, and antemortem tooth loss. No associations between pipe notches and dental pathologies, or microbial species composition,were found. Calculus samples before and after the introduction of tobacco showed highly similar species profiles. Observed interindividual microbiome differences were consistent with previously described variation in human populations from the Upper Paleolithic to the present. Dental calculus may not preserve microbial indicators of health and disease status as distinctly as dental plaque

Relation between the food environment and oral health-systematic review

BACKGROUND: There is increasing evidence that the food environment, i.e. the availability, accessibility, price and promotion of foods and beverages, has a significant influence on oral health through food consumption. With this systematic literature review, we systematically summarize the available evidence on relations between the food environment and oral health outcomes in children and adults. METHODS: English-language studies were identified through a systematic literature search, executed by a medical information specialist, on OVID/Medline, Embase, Web of Science and CINAHL. Title and abstract screening, full-text screening and quality assessment [using the Quality Assessment with Diverse Studies (QuADS) tool] were done independently by two authors. RESULTS: Twenty-three studies were included, of which 1 studied the consumer food environment (food labeling), 3 the community food environment (e.g. number of food stores in the community), 5 the organizational food environment (availability of healthy foods and beverages in schools), 2 the information environment (television advertisements) and 13 government and industry policies related to the food environment (e.g. implementation of a sugar-sweetened beverage tax). Almost all studies found that unhealthy food and beverage environments had adverse effects on oral health, and that policies improving the healthiness of food and beverage environments improved-or would improve in case of a modeling study-oral health. CONCLUSIONS: This systematic literature review provides evidence, although of low to moderate quality and available in a low quantity only, that several aspects of the food environment, especially policies affecting the food environment, are associated with oral health outcomes

A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension

Rationale The blood is a rich source of potential biomarkers for the diagnosis of idiopathic and hereditary pulmonary arterial hypertension (iPAH and hPAH, referred to as “PAH”). While a lot of biomarkers have been identified for PAH, the clinical utility of these biomarkers often remains unclear. Here, we performed an unbiased meta-analysis of published biomarkers to identify biomarkers with the highest performance for detection of PAH. Methods A literature search (in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and Wiley/Cochrane Library) was performed up to 28 January 2021. Primary end points were blood biomarker levels in PAH versus asymptomatic controls or patients suspected of pulmonary hypertension (PH) with proven normal haemodynamic profiles. Results 149 articles were identified by the literature search. Meta-analysis of 26 biomarkers yielded 17 biomarkers that were differentially expressed in PAH and non-PH control subjects. Red cell distribution width, low density lipid-cholesterol, d-dimer, N-terminal prohormone of brain natriuretic protein (NT-proBNP), interleukin-6 (IL-6) and uric acid were biomarkers with the largest observed differences, largest sample sizes and a low risk of publication bias. Receiver operating characteristic curves and sensitivity/ specificity analyses demonstrated that NT-proBNP had a high sensitivity, but low specificity for PAH. For the other biomarkers, insufficient data on diagnostic accuracy with receiver operating characteristic curves were available for meta-analysis. Conclusion This meta-analysis validates NT-proBNP as a biomarker with high sensitivity for PAH, albeit with low specificity. The majority of biomarkers evaluated in this meta-analysis lacked either external validation or data on diagnostic accuracy. Further validation studies are required as well as studies that test combinations of biomarkers to improve specificity

Oral-Functioning Questionnaires in Patients with Head and Neck Cancer: A Scoping Review

Background: Oral-functioning impairment can negatively affect the quality of life (QoL) of head and neck cancer (HNC) patients after receiving radiotherapy (RT). Assessment of patient-reported oral functioning throughout treatment can improve patient care. This scoping review aims to propose a definition for oral functioning for HNC patients and to map out the available questionnaires measuring patient-reported oral functioning in RT-treated HNC patients. Methods: A literature search in relevant databases was performed. Each questionnaire was scored on the domains validity, reliability, and responsiveness. Furthermore, the items from the questionnaires were analyzed to define the common denominators for oral functioning in HNC patients. Results: Of the 6434 articles assessed, 16 met the inclusion criteria and employed 16 distinct instruments to evaluate QoL. No questionnaire covered all oral-health-related QoL items nor assessed all aspects of validity, reliability, and responsiveness. Chewing, speaking, and swallowing were the common denominators for oral functioning. Conclusions: Based on the included studies, we suggest using the VHNSS 2.0 questionnaire to assess oral functioning in HNC patients. Furthermore, we suggest to more clearly define oral functioning in HNC patients by focusing on masticatory function (chewing and grinding), mouth opening, swallowing, speaking, and salivation

Systematic Review and Comparison of Publicly Available ICU Data Sets-A Decision Guide for Clinicians and Data Scientists.

OBJECTIVE As data science and artificial intelligence continue to rapidly gain traction, the publication of freely available ICU datasets has become invaluable to propel data-driven clinical research. In this guide for clinicians and researchers, we aim to: 1) systematically search and identify all publicly available adult clinical ICU datasets, 2) compare their characteristics, data quality, and richness and critically appraise their strengths and weaknesses, and 3) provide researchers with suggestions, which datasets are appropriate for answering their clinical question. DATA SOURCES A systematic search was performed in Pubmed, ArXiv, MedRxiv, and BioRxiv. STUDY SELECTION We selected all studies that reported on publicly available adult patient-level intensive care datasets. DATA EXTRACTION A total of four publicly available, adult, critical care, patient-level databases were included (Amsterdam University Medical Center data base [AmsterdamUMCdb], eICU Collaborative Research Database eICU CRD], High time-resolution intensive care unit dataset [HiRID], and Medical Information Mart for Intensive Care-IV). Databases were compared using a priori defined categories, including demographics, patient characteristics, and data richness. The study protocol and search strategy were prospectively registered. DATA SYNTHESIS Four ICU databases fulfilled all criteria for inclusion and were queried using SQL (PostgreSQL version 12; PostgreSQL Global Development Group) and analyzed using R (R Foundation for Statistical Computing, Vienna, Austria). The number of unique patient admissions varied between 23,106 (AmsterdamUMCdb) and 200,859 (eICU-CRD). Frequency of laboratory values and vital signs was highest in HiRID, for example, 5.2 (±3.4) lactate values per day and 29.7 (±10.2) systolic blood pressure values per hour. Treatment intensity varied with vasopressor and ventilatory support in 69.0% and 83.0% of patients in AmsterdamUMCdb versus 12.0% and 21.0% in eICU-CRD, respectively. ICU mortality ranged from 5.5% in eICU-CRD to 9.9% in AmsterdamUMCdb. CONCLUSIONS We identified four publicly available adult clinical ICU datasets. Sample size, severity of illness, treatment intensity, and frequency of reported parameters differ markedly between the databases. This should guide clinicians and researchers which databases to best answer their clinical questions

Exploring the development, evaluation and implementation of complex health interventions to prevent early childhood caries in preschool children: A scoping review protocol

OBJECTIVE: This scoping review aims to identify complex health interventions (CHI's) to prevent early childhood caries (ECC), explore the level of complexity of the identified CHI's, and explore the details of their development, evaluation, and implementation. INTRODUCTION: Many interventions to prevent ECC have multiple interacting components and can be seen as CHI's. Recent reviews on these interventions have found inconclusive effects, which may be due to differences in the development, evaluation, and implementation of CHI's. INCLUSION CRITERIA: This scoping review will consider clinical trials reporting CHI's to prevent ECC that starts during pregnancy or in the first year of life. Studies in the English language will be included regardless of the country of origin, sociocultural setting, or context. METHODS: This review will follow the Joanna Briggs Institute methodology for scoping reviews. An initial search of PubMed identified keywords and Medical Subject Headings terms. A second search of PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, ClinicalTrials.gov, and the Wiley/Cochrane Library will follow. Two independent reviewers will perform title and abstract screening, retrieve and review full-text studies, and extract data. The reference lists of all included sources will be screened for additional CHI's or relevant publications about a specific CHI. Data charting will be utilised based on study characteristics and intervention complexity. A 39-item instrument will be used to explore the details in the description of the CHI's development, evaluation, and implementation. The results will be presented in tables, visual outputs, and a narrative summary in response to the review questions. DISCUSSION: The proposed review will generate evidence which may provide a direction for the future design of studies on CHI's to prevent ECC and more complete information for those who want to adopt successful interventions to prevent ECC