Variability and bias in microbiome metagenomic sequencing: an interlaboratory study comparing experimental protocols.

Several studies have documented the significant impact of methodological choices in microbiome analyses. The myriad of methodological options available complicate the replication of results and generally limit the comparability of findings between independent studies that use differing techniques and measurement pipelines. Here we describe the Mosaic Standards Challenge (MSC), an international interlaboratory study designed to assess the impact of methodological variables on the results. The MSC did not prescribe methods but rather asked participating labs to analyze 7 shared reference samples (5 × human stool samples and 2 × mock communities) using their standard laboratory methods. To capture the array of methodological variables, each participating lab completed a metadata reporting sheet that included 100 different questions regarding the details of their protocol. The goal of this study was to survey the methodological landscape for microbiome metagenomic sequencing (MGS) analyses and the impact of methodological decisions on metagenomic sequencing results. A total of 44 labs participated in the MSC by submitting results (16S or WGS) along with accompanying metadata; thirty 16S rRNA gene amplicon datasets and 14 WGS datasets were collected. The inclusion of two types of reference materials (human stool and mock communities) enabled analysis of both MGS measurement variability between different protocols using the biologically-relevant stool samples, and MGS bias with respect to ground truth values using the DNA mixtures. Owing to the compositional nature of MGS measurements, analyses were conducted on the ratio of Firmicutes: Bacteroidetes allowing us to directly apply common statistical methods. The resulting analysis demonstrated that protocol choices have significant effects, including both bias of the MGS measurement associated with a particular methodological choices, as well as effects on measurement robustness as observed through the spread of results between labs making similar methodological choices. In the analysis of the DNA mock communities, MGS measurement bias was observed even when there was general consensus among the participating laboratories. This study was the result of a collaborative effort that included academic, commercial, and government labs. In addition to highlighting the impact of different methodological decisions on MGS result comparability, this work also provides insights for consideration in future microbiome measurement study design.

Spatiotemporal link between El Niño Southern Oscillation (ENSO), extreme heat, and thermal stress in the Asia-Pacific region.

Climate change is closely monitored and numerous studies reports increasing air temperature and weather extremes across the globe. As a direct consequence of the increase of global temperature, the increased heat stress is becoming a global threat to public health. While most climate change and epidemiological studies focus on air temperature to explain the increasing risks, heat strain can be predicted using comprehensive indices such as Universal Thermal Climate Index (UTCI). The Asia-Pacific region is prone to thermal stress and the high population densities in the region impose high health risk. This study evaluated the air temperature and UTCI trends between 1990 and 2019 and found significant increasing trends for air temperature for the whole region while the increases of UTCI are not as pronounced and mainly found in the northern part of the region. These results indicate that even though air temperature is increasing, the risks of heat stress when assessed using UTCI may be alleviated by other factors. The associations between El Niño Southern Oscillation (ENSO) and heat stress was evaluated on a seasonal level and the strongest regional responses were found during December-January (DJF) and March-May (MAM).

Edible flora in pre-Columbian Caribbean coprolites: Expected and unexpected data.

Coprolites, or mummified feces, are valuable sources of information on ancient cultures as they contain ancient DNA (aDNA). In this study, we analyzed ancient plant DNA isolated from coprolites belonging to two pre-Columbian cultures (Huecoid and Saladoid) from Vieques, Puerto Rico, using shotgun metagenomic sequencing to reconstruct diet and lifestyles. We also analyzed DNA sequences of putative phytopathogenic fungi, likely ingested during food consumption, to further support dietary habits. Our findings show that pre-Columbian Caribbean cultures had a diverse diet consisting of maize (Zea mays), sweet potato (Ipomoea batatas), chili peppers (Capsicum annuum), peanuts (Arachis spp.), papaya (Carica papaya), tomato (Solanum lycopersicum) and, very surprisingly cotton (Gossypium barbadense) and tobacco (Nicotiana sylvestris). Modelling of putative phytopathogenic fungi and plant interactions confirmed the potential consumption of these plants as well as edible fungi, particularly Ustilago spp., which suggest the consumption of maize and huitlacoche. These findings suggest that a variety of dietary, medicinal, and hallucinogenic plants likely played an important role in ancient human subsistence and societal customs. We compared our results with coprolites found in Mexico and the United States, as well as present-day faeces from Mexico, Peru, and the United States. The results suggest that the diet of pre-Columbian cultures resembled that of present-day hunter-gatherers, while agriculturalists exhibited a transitional state in dietary lifestyles between the pre-Columbian cultures and larger scale farmers and United States individuals. Our study highlights differences in dietary patterns related to human lifestyles and provides insight into the flora present in the pre-Columbian Caribbean area. Importantly, data from ancient fecal specimens demonstrate the importance of ancient DNA studies to better understand pre-Columbian populations.

Incidence of opioid misuse by cigarette smoking status in the United States.

BACKGROUND: The combination of opioid misuse and cigarette smoking contributes to increased morbidity and mortality compared to each substance use alone. We estimated the incidence of opioid misuse for persons who currently or formerly smoked versus never smoked. METHODS: Data came from the 2015-2020 National Surveys on Drug Use and Health cross-sectional surveys of US civilians aged 12+ (n = 315,661). Weighted opioid misuse incidence and average time between cigarette use initiation and opioid misuse initiation were calculated annually by smoking status. Logistic regression models tested time trends in incidence by smoking status. RESULTS: Overall, 0.75% of persons initiated opioid misuse per year; opioid misuse incidence was 1.35% for those who currently smoked cigarettes, 0.54% for those who formerly smoked, and 0.67% for those who never smoked. For persons who currently smoked and misused opioids (1.50%), 95.08% smoked prior to opioid use. The average time between smoking followed by opioid misuse was 12.93 years and for opioid misuse followed by smoking was 4.36 years. Persons who currently smoked were more likely to initiate opioid misuse than those who had never smoked (AOR = 1.81, 95% CI: 1.60, 2.06). There was a decrease in the opioid misuse incidence over time (AOR = 0.90; 95% CI: 0.85, 0.92), which did not differ by smoking status. CONCLUSIONS: Persons who currently smoked cigarettes, relative to those who never smoked, were more likely to initiate opioid misuse. As most individuals smoked before opioid misuse, it may be useful for primary prevention efforts to decrease opioid misuse initiation by focusing on smoking status.

Accelerating Gut Microbiome Research with Robust Sample Collection.

Background: Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods: We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bioinformatic analyses were used to examine the microbiome composition. Results: The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also resulted in varying microbiome profiles. Homogenization and stabilization at 4°C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely because of the freeze/thaw. Conclusion: The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization and stabilization at 4°C for 24 hours provides a neat, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease.

Longitudinal associations between receiving E-cigarette price promotions and subsequent E-cigarette use among U.S. Young adult cigarette smokers.

INTRODUCTION: E-cigarette price promotions (EPPs; i.e., marketed reductions in cost) may influence young adult cigarette smokers to try, dual use with, or completely transition to e-cigarettes. We assessed whether receiving EPPs was associated with subsequent e-cigarette use among this group. METHODS: Data were from Waves 4 (2016-2018) and 5 (2018-2019) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study survey. Analysis was restricted to participants who were young adult (18-34 years) established, current cigarette smokers who did not use e-cigarettes at Wave 4 (baseline; n = 2,664; Sample 1), and a subsample of those who tried to quit smoking completely in the past year at Wave 5 (follow-up; n = 948; Sample 2). Multivariable logistic regressions were used to examine associations between receiving EPPs at baseline and past year use of e-cigarettes in general (Sample 1) and to help quit smoking (Sample 2) at follow-up, controlling for covariates. RESULTS: Overall, 4.1% and 4.9% of Sample 1 and 2 participants received EPPs, respectively; At follow-up, 33.4% of Sample 1 participants used e-cigarettes, and 12.0% of Sample 2 participants used e-cigarettes to quit smoking. Receiving EPPs was associated with subsequent past-year e-cigarette use in general (AOR = 2.07; 95% CI = 1.31 to 3.27), and past-year e-cigarette use to help with quitting smoking (AOR = 3.20; 95% CI = 1.48 to 6.90). DISCUSSION: EPPs may increase e-cigarette use among established, current smokers and may be used to quit smoking. Research is needed to understand how EPPs may be differentially associated with complete product transition versus dual/poly use among young adult smokers.

Associations between living in localities with e-cigarette sales restrictions and e-cigarette use change among young adults in Los Angeles County.

INTRODUCTION: Local e-cigarette sales restrictions (ESRs) may impact e-cigarette use. This study examined the associations between living in localities with various ESR policies and changes in e-cigarette use among young adults in Los Angeles (LA) County, California, USA. METHODS: Data were from a cohort of LA County young adults (18-21 years; n=2100) who completed two waves of surveys (Fall 2018-Summer 2019 and Summer-Fall 2020). Local flavoured (n=9) and comprehensive (n=2) ESRs in LA County implemented between June 2019 and May 2020 were identified, coded and merged with the baseline data. Multivariable logistic regressions were used to examine the associations between living in ESR localities and e-cigarette use at follow-up, controlling for covariates and stratified by cigarette smoking at baseline. RESULTS: Overall, 20.9% and 14.3% of participants lived in localities with flavoured and comprehensive ESRs, respectively. Participants who were non-Hispanic, had higher socioeconomic statuses and were currently using e-cigarettes were generally more likely to live in ESR localities than their counterparts. The associations between living in ESR localities and e-cigarette use at follow-up were not found among baseline non-e-cigarette users regardless of their cigarette smoking status; a positive relationship was found among baseline e-cigarette users who also smoked cigarettes but not among non-smokers. DISCUSSION: Participants who lived in localities with various ESR policies were different in their baseline e-cigarette use and socioeconomic backgrounds. Future research examining the potential impact of ESRs on e-cigarette use change should consider the localities' overall sociodemographic and tobacco-using characteristics and individuals' cigarette smoking histories.

Longitudinal associations between U.S. youth exposure to E-cigarette marketing and E-cigarette use harm perception and behavior change.

E-cigarette marketing tactics to reach and appeal to youth are rapidly changing. This study examined to what extent youth e-cigarette marketing exposure was associated with e-cigarette use behavior change one year later, during a time when youth e-cigarette use was starting to surge in the U.S. Using nationally representative longitudinal public-use data from the Population Assessment of Tobacco and Health (PATH) Study, we examined associations between recalled e-cigarette marketing exposure (2016-2018) at Wave (W) 4 and e-cigarette use harm perception and behavior change (ever, current, and regular use) one year later (W4.5; 2017-2018) among W4 never tobacco users (n = 9405). Recall of exposure to e-cigarette marketing through different channels was also examined in multivariable models controlling for socio-demographic factors and established e-cigarette use risk factors. Results show that the most frequently recalled channels of e-cigarette marketing exposure were retail stores (50.3%), television (22.2%), and websites/social media (20.2%). Over one year, 21.2%, 7.8%, 3.4%, and 1.2% of respondents reported reduced harm perceptions, and ever, current, and regular use of e-cigarettes, respectively, at follow-up. Recalled exposure to e-cigarette marketing was associated with reduced e-cigarette harm perception (AOR = 1.20; 95% CI = 1.05-1.37) and ever (AOR = 1.26; 95% CI = 1.01-1.56) and current use (AOR = 1.40; 95% CI = 1.02-1.92) at follow-up. E-cigarette marketing exposure through websites/social media was associated with reduced harm perceptions and all stages of e-cigarette use change, including regular use. Identifying marketing techniques and channels that change youth e-cigarette harm perceptions and influence e-cigarette use progression is essential to inform e-cigarette regulatory policies and prevention campaigns.

Comparison of a formatted versus traditional sign out process for physicians in the emergency department.

INTRODUCTION: Frequent interruptions, critically ill patients, and high patient turnover can make Emergency Department (ED) physician transitions of care (TOCs) challenging. Currently, there is no strict format for TOC in the ED. We structured a formatted ED TOC and evaluated the comparative effects from traditional TOC practice on the perceived quality of sign-out among physicians working in the ED. METHODS: We performed a prospective pre/post-interventional study utilizing convenience sampling in an urban community teaching hospital. The primary outcome was perceived quality of sign-out, as evaluated by the incoming physician one-hour after TOC, using the handoff-Clinical Evaluation Exercise (h-CEX) score with a 9-point scale for each category: Organized/Efficient, Communications Skills, Included Pertinent Information, Clinical Judgment, Patient Focused, Setting, and Overall Sign-Out Quality. Additional evaluation of unexpected tasks and errors from TOC w performed. RESULTS: We included 344 patient TOC observed, of which 147 (43%) were formatted interventions while 197 (57%) were standard TOCs. After analysis in a random effects model, statistically significant improvements among resident physicians were seen for the formatted TOC: patient focused (mean difference 0.40), setting (mean difference 1.05), and overall (mean difference 0.68). The rate of unexpected tasks and errors were higher in the standard TOC, though not statistically significant. CONCLUSION: Resident physicians saw improvement in several h-CEX categories with a formatted TOC. Consistent with prior studies, a formatted TOC for emergency medicine should be strongly considered, especially among learners.

Visual Attention to Health Warning Labels on Waterpipe Venue Menus in Immersive Virtual Reality.

INTRODUCTION: This study examined how health warning labels (HWL) on a waterpipe venue menu captured and held the attention of consumers and influenced waterpipe tobacco smoking (WTS) attitudes, beliefs, and behaviors. AIMS AND METHODS: A randomized experiment (N = 96) of young adult waterpipe smokers was conducted in an immersive virtual reality laboratory. Participants viewed one of two virtual reality scenarios, a menu with an HWL and nicotine concentration or menu without an HWL and nicotine concentration. Eye-tracking metrics were collected, and participants completed posttest questionnaires on demographics, tobacco use history, and WTS attitudes, beliefs, and behaviors. T-tests were used to assess group differences, and a mediation analysis conducted to examine the relationship between the HWL and intention to quit WTS. RESULTS: Participants in the HWL group demonstrated greater visual attention to the warning and nicotine areas and less visual attention to the flavor and ingredients areas of the menu compared to the control group. The HWL group demonstrated greater negative attitudes toward WTS (p = .002), greater perceived risk of decreased lung function (p = .026), and greater intention to quit WTS (p = 0.003). The mediation model indicated the relationship between the HWL on a menu and intention to quit WTS was mediated by an increase in negative attitudes toward WTS. CONCLUSIONS: The HWLs on a menu captured and held the attention of consumers and increased negative attitudes, perceptions of health risk, and intention to quit WTS indicating potential benefit of including a warning label or nicotine concentration on menus to correct misperceptions of WTS. IMPLICATIONS: The study contributes to the broader literature on communicating the harms and risks of WTS. The findings suggest that HWL and nicotine concentration on waterpipe venue menus attract attention from consumers in environments comparable to the real world and the strategy warrants further exploration as a targeted policy intervention to educate the public and reduce the health burden of WTS.

A mobile lab for ancient DNA extraction in Perug.

We report the use of a mobile laboratory set up to extract ancient DNA (aDNA) from 34 human coprolites (fossilized faeces) samples. Our approach enabled the rapid genetic characterization of 5,000 years old archeological samples. It is useful for the on-site screening of museums and freshly excavated samples for DNA. This approach is accessible to other investigators as the mobile laboratory was set up using commercially available instruments.

Health Information on Waterpipe Lounge Menus to Educate Young Adults: Pilot Study Findings.

BACKGROUND: For years, tobacco risk communication has largely focused on cigarette smoking. New strategies must be developed to adapt to emerging tobacco products, such as waterpipe tobacco smoking (WTS). AIMS: The purpose of this pilot study was to determine the preliminary effects of health information on waterpipe lounge menus on the perceptions of harm and risk from WTS and inform future efficacy interventions for health communication (i.e., educating populations on the risks, harms, and health consequences of WTS). METHOD: Participants aged 18 to 24 years (n = 213) who smoked waterpipe at least monthly were randomized to one of four waterpipe lounge menu groups using a two-by-two experimental design with "warning message" and "nicotine content" as factors. RESULTS: Those who viewed waterpipe lounge menus that included a warning message had greater perceived relative harm to health and perceived risk of decreased lung function from WTS. Those who viewed waterpipe lounge menus that included nicotine content had greater perceived risk of heart attack from WTS. DISCUSSION: Participants who were exposed to health warnings of WTS and information on the nicotine content of waterpipe tobacco increased on measures of perceived relative harm and risk of health consequences. CONCLUSION: The pilot test results indicate promise for providing health information on waterpipe lounge menus to educate young adults on the harms and risks of WTS.

Forecasting COVID-19 Cases Based on Social Distancing in Maryland, USA: A Time-Series Approach.

OBJECTIVE: Our objective is to forecast the number of coronavirus disease 2019 (COVID-19) cases in the state of Maryland, United States, using transfer function time series (TS) models based on a Social Distancing Index (SDI) and determine how their parameters relate to the pandemic mechanics. METHODS: A moving window of 2 mo was used to train the transfer function TS model that was then tested on the next week data. After accounting for a secular trend and weekly cycle of the SDI, a high correlation was documented between it and the daily caseload 9 days later. Similar patterns were also observed on the daily COVID-19 cases and incorporated in our models. RESULTS: In most cases, the proposed models provide a reasonable performance that was, on average, moderately better than that delivered by TS models based only on previous observations. The model coefficients associated with the SDI were statistically significant for most of the training/test sets. CONCLUSIONS: Our proposed models that incorporate SDI can forecast the number of COVID-19 cases in a region. Their parameters have real-life interpretations and, hence, can help understand the inner workings of the epidemic. The methods detailed here can help local health governments and other agencies adjust their response to the epidemic.

Impact of irrigation water type and sampling frequency on Microbial Water Quality Profiles required for compliance with U.S. Food Safety Modernization Act Produce Safety Rule standards.

The U.S. Food Safety Modernization Act (FSMA) Produce Safety Rule (PSR) requires that farmers generate a Microbial Water Quality Profile (MWQP) from 20 samples per agricultural water source, taken over 2-4 years and five annual samples thereafter. Farmers must use the MWQP to ascertain a geometric mean (GM) of ≤126 CFU/100 mL and statistical threshold value (STV) of ≤410 CFU/100 mL of generic Escherichia coli. Farmers are responsible for collecting samples and paying for testing, incurring a financial and time burden. To determine if testing frequency can be reduced without compromising accuracy, water samples (n = 279) were collected from twelve sites in the U.S. Mid-Atlantic region from 2016 to 2018 comprising tidal brackish river, non-tidal fresh river, pond, vegetable processing, and reclaimed water. The GM and STV were calculated for all sites and water types using all samples, and for multiple sub-samples of <20 from each site and water type. A Monte Carlo simulation was used to determine the proportion of sub-sample sizes that yielded the same determination as the entire sample size of PSR standard compliance. Four sites, two pond and two reclaimed water sites, complied with PSR GM and STV requirements when using the entire sample set. When a water source's calculated GM and STV using the entire sample set hovered close to the PSR thresholds, sub-sample sizes approached the recommended 20 samples to reach a congruent compliance determination. However, 99% agreement was obtained with a sub-sample of five when the absolute difference between the GM and STV from total samples and the PSR thresholds was ≥2.6 and 4.5 log CFU/100 mL E. coli, respectively. These findings suggest that under certain conditions the MWQP may be generated with well below 20 samples, reducing the economic burden on farmers while still maintaining a representative MWQP.

El Niño Southern Oscillation, monsoon anomaly, and childhood diarrheal disease morbidity in Nepal.

Climate change is adversely impacting the burden of diarrheal diseases. Despite significant reduction in global prevalence, diarrheal disease remains a leading cause of morbidity and mortality among young children in low- and middle-income countries. Previous studies have shown that diarrheal disease is associated with meteorological conditions but the role of large-scale climate phenomena such as El Niño-Southern Oscillation (ENSO) and monsoon anomaly is less understood. We obtained 13 years (2002-2014) of diarrheal disease data from Nepal and investigated how the disease rate is associated with phases of ENSO (El Niño, La Niña, vs. ENSO neutral) monsoon rainfall anomaly (below normal, above normal, vs. normal), and changes in timing of monsoon onset, and withdrawal (early, late, vs. normal). Monsoon season was associated with a 21% increase in diarrheal disease rates (Incident Rate Ratios [IRR]: 1.21; 95% CI: 1.16-1.27). El Niño was associated with an 8% reduction in risk while the La Niña was associated with a 32% increase in under-5 diarrheal disease rates. Likewise, higher-than-normal monsoon rainfall was associated with increased rates of diarrheal disease, with considerably higher rates observed in the mountain region (IRR 1.51, 95% CI: 1.19-1.92). Our findings suggest that under-5 diarrheal disease burden in Nepal is significantly influenced by ENSO and changes in seasonal monsoon dynamics. Since both ENSO phases and monsoon can be predicted with considerably longer lead time compared to weather, our findings will pave the way for the development of more effective early warning systems for climate sensitive infectious diseases.

Manual Palpation vs. Femoral Arterial Doppler Ultrasound for Comparison of Pulse Check Time During Cardiopulmonary Resuscitation in the Emergency Department: A Pilot Study.

BACKGROUND: Manual palpation (MP) is frequently employed for pulse checks, but studies have shown that trained medical personnel have difficulty accurately identifying pulselessness or return of spontaneous circulation (ROSC) using MP. Any delays in identifying pulselessness can lead to significant delays in starting or resuming high-quality chest compressions. OBJECTIVES: This study explored whether femoral arterial Doppler ultrasound (FADU) decreases pulse check duration during cardiopulmonary resuscitation (CPR) compared with MP among patients in the emergency department (ED) receiving CPR directed by emergency medicine physicians who had received minimal additional didactic ultrasound training. METHODS: We performed a prospective observational cohort study from October 2018 to May 2019 at an urban community ED. Using convenience sampling, we enrolled patients arriving at our ED or who decompensated during their ED stay and received CPR. For continuous data, median (interquartile range [IQR]) were calculated, and medians were compared using Kruskal-Wallis test. RESULTS: Fifty-two eligible patients were enrolled and 135 pulse checks via MP and 35 via FADU were recorded. MP observations had a median (IQR) of 11.00 (7.36-15.48) s, whereas FADU had a median (IQR) of 8.98 (5.45-13.85) s. There was a difference between the two medians of 2.02 s (p = 0.05). CONCLUSIONS: In this study, the use of FADU was superior to MP in achieving shorter pulse check times. Further research is needed to confirm the accuracy of FADU for identifying ROSC as well as to determine whether FADU can improve clinical outcomes.

Racial and Sex Differences between Urinary Phthalates and Metabolic Syndrome among U.S. Adults: NHANES 2005-2014.

Phthalates, plasticizers ubiquitous in household and personal care products, have been associated with metabolic disturbances. Despite the noted racial differences in phthalate exposure and the prevalence of metabolic syndrome (MetS), it remains unclear whether associations between phthalate metabolites and MetS vary by race and sex. A cross-sectional analysis was conducted among 10,017 adults from the National Health and Nutritional Examination Survey (2005-2014). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated for the association between 11 urinary phthalate metabolites and MetS using weighted sex and race stratified multivariable logistic regression. Higher MCOP levels were significantly associated with increased odds of MetS among women but not men, and only remained significant among White women (POR Q4 vs. Q1 = 1.68, 95% CI: 1.24, 2.29; p-trend = 0.001). Similarly, the inverse association observed with MEHP among women, persisted among White women only (POR Q4 vs. Q1 = 0.53, 95% CI: 0.35, 0.80; p-trend = 0.003). However, ΣDEHP metabolites were associated with increased odds of MetS only among men, and this finding was limited to White men (POR Q4 vs. Q1 = 1.54, 95% CI: 1.01, 2.35; p-trend = 0.06). Among Black men, an inverse association was observed with higher MEP levels (POR Q4 vs. Q1 = 0.43, 95% CI: 0.24, 0.77; p-trend = 0.01). The findings suggest differential associations between phthalate metabolites and MetS by sex and race/ethnicity.

Biomarker Categorization in Transcriptomic Meta-Analysis by Concordant Patterns With Application to Pan-Cancer Studies.

With the increasing availability and dropping cost of high-throughput technology in recent years, many-omics datasets have accumulated in the public domain. Combining multiple transcriptomic studies on related hypothesis via meta-analysis can improve statistical power and reproducibility over single studies. For differential expression (DE) analysis, biomarker categorization by DE pattern across studies is a natural but critical task following biomarker detection to help explain between study heterogeneity and classify biomarkers into categories with potentially related functionality. In this paper, we propose a novel meta-analysis method to categorize biomarkers by simultaneously considering the concordant pattern and the biological and statistical significance across studies. Biomarkers with the same DE pattern can be analyzed together in downstream pathway enrichment analysis. In the presence of different types of transcripts (e.g., mRNA, miRNA, and lncRNA, etc.), integrative analysis including miRNA/lncRNA target enrichment analysis and miRNA-mRNA and lncRNA-mRNA causal regulatory network analysis can be conducted jointly on all the transcripts of the same category. We applied our method to two Pan-cancer transcriptomic study examples with single or multiple types of transcripts available. Targeted downstream analysis identified categories of biomarkers with unique functionality and regulatory relationships that motivate new hypothesis in Pan-cancer analysis.

Public Compliance With Social Distancing Measures and SARS-CoV-2 Spread : A Quantitative Analysis of 5 States.

OBJECTIVE: We quantified the association between public compliance with social distancing measures and the spread of SARS-CoV-2 during the first wave of the epidemic (March-May 2020) in 5 states that accounted for half of the total number of COVID-19 cases in the United States. METHODS: We used data on mobility and number of COVID-19 cases to longitudinally estimate associations between public compliance, as measured by human mobility, and the daily reproduction number and daily growth rate during the first wave of the COVID-19 epidemic in California, Illinois, Massachusetts, New Jersey, and New York. RESULTS: The 5 states mandated social distancing directives during March 19-24, 2020, and public compliance with mandates started to decrease in mid-April 2020. As of May 31, 2020, the daily reproduction number decreased from 2.41-5.21 to 0.72-1.19, and the daily growth rate decreased from 0.22-0.77 to -0.04 to 0.05 in the 5 states. The level of public compliance, as measured by the social distancing index (SDI) and daily encounter-density change, was high at the early stage of implementation but decreased in the 5 states. The SDI was negatively associated with the daily reproduction number (regression coefficients range, -0.04 to -0.01) and the daily growth rate (from -0.009 to -0.01). The daily encounter-density change was positively associated with the daily reproduction number (regression coefficients range, 0.24 to 1.02) and the daily growth rate (from 0.05 to 0.26). CONCLUSIONS: Social distancing is an effective strategy to reduce the incidence of COVID-19 and illustrates the role of public compliance with social distancing measures to achieve public health benefits.