Publications by authors named "Vasilis Vasiliou"

193 Publications

A Novel Technique for Redox Lipidomics Using Mass Spectrometry: Application on Vegetable Oils Used to Fry Potatoes.

J Am Soc Mass Spectrom 2021 Jun 7. Epub 2021 Jun 7.

School of Nutrition, Kinesiology and Psychological Science, University of Central Missouri, Warrensburg, Missouri 64093, United States.

Vegetables oils, rich in polyunsaturated fatty acids, are vulnerable to oxidation during manufacturing, processing, and food preparation. Currently, individual oxidation products are not well characterized, and hence, the health impacts of these unique lipid species remain unknown. Here, we introduce an extensive oxidized lipidomics tandem mass spectrometry library and integrate these libraries within a user-friendly software covering a comprehensive redox lipidomics workflow. We apply this workflow to olive, soy, and walnut cooking oil; comparing unheated oil, oil after deep frying potatoes, and oil after oven frying potatoes. We annotated over a thousand oxidized triglycerides across 273 features (many coeluted). This software was validated against traditional chemical assays of oxidation, known oxidized lipids in castor oil, synthesized standards, and an alternate software LPPtiger. Development of these new software programs for redox lipidomics opens the door to characterize health implications of individual oxidation products.
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http://dx.doi.org/10.1021/jasms.1c00150DOI Listing
June 2021

Reducing drug-use harms among higher education students: MyUSE contextual-behaviour change digital intervention development using the Behaviour Change Wheel.

Harm Reduct J 2021 May 20;18(1):56. Epub 2021 May 20.

Student Health Department, University College Cork, Ardpatrick College Road, Cork, Ireland.

Background: Digital harm-reduction interventions typically focus on people with severe drug-use problems, yet these interventions have moderate effectiveness on drug-users with lower levels of risk of harm. The difference in effectiveness may be explained by differences in behavioural patterns between the two groupings. Harnessing behavioural theories to understand what is at the core of drug-use behaviours and mapping the content of new interventions, may improve upon the effectiveness of interventions for lower-risk drug-users. To the best of our knowledge, this is the first study to systematically apply the Behaviour Change Wheel (BCW) approach to understand the components, influencing capabilities, opportunities, and motivations (COM-B) of higher education students to change their drug-use behaviors. It is also the first study which identifies specific patterns of behaviours that are more responsive to harm reduction practices through the use of the Theoretical Domain Framework (TDF).

Methods: We employed an explanatory sequential mix-method design. We first conducted an on-line survey and a Delphi exercise to understand the factors influencing COM-B components of higher education students to change their drug-use. Subsequently, we mapped all evidence onto the COM-B components and the TDF domains to identify clusters of behaviours to target for change, using a pattern-based discourse analysis. Finally, a series of multidisciplinary group meetings identified the intervention functions-the means by which the intervention change targeted behaviours and the Behavioural Change Techniques (BCTs) involved using the behaviour change technique taxonomy (v.1).

Results: Twenty-nine BCTs relevant to harm-reduction practices were identified and mapped across five intervention functions (education, modelling, persuasion, incentivization, and training) and five policy categories (communication/marketing, guidelines, regulation, service provision, and environmental/social planning). These BCTs were distributed across eight identified saturated clusters of behaviours MyUSE intervention attempts to change.

Conclusions: The BCTs, identified, will inform the development of a digitally delivered behaviour change intervention that focuses on increasing mindful decision-making with respect to drug-use and promotes alternatives to drug-use activities. The findings can also inform implementation scientists in applying context-specific harm-reduction practices in higher education. We present examples of how the eight identified clusters of target behaviours are mapped across the COM-B components and the TDF, along with suggestions of implementation practices for harm reduction at student population level.
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http://dx.doi.org/10.1186/s12954-021-00491-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136195PMC
May 2021

COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy.

Hum Genomics 2021 05 10;15(1):27. Epub 2021 May 10.

Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, Queensland, 4878, Australia.

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.
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http://dx.doi.org/10.1186/s40246-021-00326-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107019PMC
May 2021

Illness Perceptions of COVID-19 in Europe: Predictors, Impacts and Temporal Evolution.

Front Psychol 2021 14;12:640955. Epub 2021 Apr 14.

Department of Psychology, University of Cyprus, Nicosia, Cyprus.

Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors. This was a time-series-cross-section study of 7,032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors. There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context. The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution.
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http://dx.doi.org/10.3389/fpsyg.2021.640955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079952PMC
April 2021

In Silico Exploration of the Potential Role of Acetaminophen and Pesticides in the Etiology of Autism Spectrum Disorder.

Toxics 2021 Apr 27;9(5). Epub 2021 Apr 27.

Environmental Health Sciences Department, Yale School of Public Health, New Haven, CT 06510, USA.

Recent epidemiological studies suggest that prenatal exposure to acetaminophen (APAP) is associated with increased risk of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder affecting 1 in 59 children in the US. Maternal and prenatal exposure to pesticides from food and environmental sources have also been implicated to affect fetal neurodevelopment. However, the underlying mechanisms for ASD are so far unknown, likely with complex and multifactorial etiology. The aim of this study was to explore the potential effects of APAP and pesticide exposure on development with regards to the etiology of ASD by highlighting common genes and biological pathways. Genes associated with APAP, pesticides, and ASD through human research were retrieved from molecular and biomedical literature databases. The interaction network of overlapping genetic associations was subjected to network topology analysis and functional annotation of the resulting clusters. These genes were over-represented in pathways and biological processes (FDR < 0.05) related to apoptosis, metabolism of reactive oxygen species (ROS), and carbohydrate metabolism. Since these three biological processes are frequently implicated in ASD, our findings support the hypothesis that cell death processes and specific metabolic pathways, both of which appear to be targeted by APAP and pesticide exposure, may be involved in the etiology of ASD. This novel exposures-gene-disease database mining might inspire future work on understanding the biological underpinnings of various ASD risk factors.
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http://dx.doi.org/10.3390/toxics9050097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146009PMC
April 2021

Patterns of Psychological Responses among the Public during the Early Phase of COVID-19: A Cross-Regional Analysis.

Int J Environ Res Public Health 2021 04 14;18(8). Epub 2021 Apr 14.

Clinic for Psychiatry, Clinical Center of Montenegro, 81110 Podgorica, Montenegro.

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all s = 0.001-0.021). Seeking social support was the significant mediator across subgroups (all s range = <0.001-0.005) except from the Hong Kong sample ( = 0.06) and the North and South American sample ( = 0.53). No mediation was found for problem-solving (except from the Northern European sample, = 0.009). Prosociality was the significant mediator in the Hong Kong sample ( = 0.016) and the Eastern European sample ( = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions.
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http://dx.doi.org/10.3390/ijerph18084143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070933PMC
April 2021

Evolution of the liver biopsy and its future.

Transl Gastroenterol Hepatol 2021 5;6:20. Epub 2021 Apr 5.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.

Liver biopsies are commonly used to evaluate a wide variety of medical disorders, including neoplasms and post-transplant complications. However, its use is being impacted by improved clinical diagnosis of disorders, and non-invasive methods for evaluating liver tissue and as a result the indications of a liver biopsy have undergone major changes in the last decade. The evolution of highly effective treatments for some of the common indications for liver biopsy in the last decade (e.g., viral hepatitis B and C) has led to a decline in the number of liver biopsies in recent years. At the same time, the emergence of better technologies for histologic evaluation, tissue content analysis and genomics are among the many new and exciting developments in the field that hold great promise for the future and are going to shape the indications for a liver biopsy in the future. Recent advances in slide scanners now allow creation of "digital/virtual" slides that have image of the entire tissue section present in a slide [whole slide imaging (WSI)]. WSI can now be done very rapidly and at very high resolution, allowing its use in routine clinical practice. In addition, a variety of technologies have been developed in recent years that use different light sources and/or microscopes allowing visualization of tissues in a completely different way. One such technique that is applicable to liver specimens combines multiphoton microscopy (MPM) with advanced clearing and fluorescent stains known as Clearing Histology with MultiPhoton Microscopy (CHiMP). Although it has not yet been extensively validated, the technique has the potential to decrease inefficiency, reduce artifacts, and increase data while being readily integrable into clinical workflows. Another technology that can provide rapid and in-depth characterization of thousands of molecules in a tissue sample, including liver tissues, is matrix assisted laser desorption/ionization (MALDI) mass spectrometry. MALDI has already been applied in a clinical research setting with promising diagnostic and prognostic capabilities, as well as being able to elucidate mechanisms of liver diseases that may be targeted for the development of new therapies. The logical next step in huge data sets obtained from such advanced analysis of liver tissues is the application of machine learning (ML) algorithms and application of artificial intelligence (AI), for automated generation of diagnoses and prognoses. This review discusses the evolving role of liver biopsies in clinical practice over the decades, and describes newer technologies that are likely to have a significant impact on how they will be used in the future.
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http://dx.doi.org/10.21037/tgh.2020.04.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829074PMC
April 2021

Yale School of Public Health Symposium: An overview of the challenges and opportunities associated with per- and polyfluoroalkyl substances (PFAS).

Sci Total Environ 2021 Jul 3;778:146192. Epub 2021 Mar 3.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA. Electronic address:

On December 13, 2019, the Yale School of Public Health hosted a symposium titled "Per- and Polyfluoroalkyl Substances (PFAS): Challenges and Opportunities" in New Haven, Connecticut. The meeting focused on the current state of the science on these chemicals, highlighted the challenges unique to PFAS, and explored promising opportunities for addressing them. It brought together participants from Yale University, the National Institute of Environmental Health Sciences, the University of Massachusetts Amherst, the University of Connecticut, the Connecticut Agricultural Experiment Station, the Connecticut Departments of Public Health and Energy and Environmental Protection, and the public and private sectors. Presentations during the symposium centered around several primary themes. The first reviewed the current state of the science on the health effects associated with PFAS exposure and noted key areas that warranted future research. As research in this field relies on specialized laboratory analyses, the second theme considered commercially available methods for PFAS analysis as well as several emerging analytical approaches that support health studies and facilitate the investigation of a broader range of PFAS. Since mitigation of PFAS exposure requires prevention and cleanup of contamination, the third theme highlighted new nanotechnology-enabled PFAS remediation technologies and explored the potential of green chemistry to develop safer alternatives to PFAS. The fourth theme covered collaborative efforts to assess the vulnerability of in-state private wells and small public water supplies to PFAS contamination by adjacent landfills, and the fifth focused on strategies that promote successful community engagement. This symposium supported a unique interdisciplinary coalition established during the development of Connecticut's PFAS Action Plan, and discussions occurring throughout the symposium revealed opportunities for collaborations among Connecticut scientists, state and local officials, and community advocates. In doing so, it bolstered the State of Connecticut's efforts to implement the ambitious initiatives that its PFAS Action Plan recommends.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146192DOI Listing
July 2021

Identification of dose-dependent DNA damage and repair responses from subchronic exposure to 1,4-dioxane in mice using a systems analysis approach.

Toxicol Sci 2021 Mar 10. Epub 2021 Mar 10.

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06250, USA.

1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.
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http://dx.doi.org/10.1093/toxsci/kfab030DOI Listing
March 2021

Standardized nomenclature and open science in Human Genomics.

Hum Genomics 2021 Feb 22;15(1):13. Epub 2021 Feb 22.

Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, Queensland, 4878, Australia.

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http://dx.doi.org/10.1186/s40246-021-00312-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898730PMC
February 2021

Use of Untargeted Metabolomics to Explore the Air Pollution-Related Disease Continuum.

Curr Environ Health Rep 2021 03 9;8(1):7-22. Epub 2021 Jan 9.

Department of Surgery, School of Medicine, Yale University, New Haven, USA.

Purpose Of Review: The purpose of this review is to summarize the application of untargeted metabolomics to identify the perturbation of metabolites or metabolic pathways associated with air pollutant exposures.

Recent Findings: Twenty-three studies were included in this review, in adults, children, or pregnant women. The most commonly measured air pollutant is particulate matter smaller than 2.5 μm. Size-fractioned particles, particle chemical species, gas pollutants, or organic compounds were also investigated. The reviewed studies used a wide range of air pollution measurement techniques and metabolomics analyses. Identified metabolites were primarily related to oxidative stress and inflammatory responses, and a few were related to the alterations of steroid metabolic pathways. The observed metabolic perturbations can differ by disease status, sex, and age. Air pollution-related metabolic changes were also associated with health outcomes in some studies. Our review shows that air pollutant exposures are associated with metabolic pathways primarily related to oxidative stress, inflammation, as assessed through untargeted metabolomics in 23 studies. More metabolomic studies with larger sample sizes are needed to identify air pollution components most responsible for adverse health effects, elaborate on mechanisms for subpopulation susceptibility, and link air pollution exposure to specific adverse health effects.
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http://dx.doi.org/10.1007/s40572-020-00298-xDOI Listing
March 2021

Alcohol consumption and risk of stomach cancer: A meta-analysis.

Chem Biol Interact 2021 Feb 4;336:109365. Epub 2021 Jan 4.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Stomach cancer is one of the most common cancers in the world. The relationship between alcohol consumption and the risk of stomach cancer remains unclear. Epidemiology studies investigating this relationship have shown inconsistent findings. A meta-analysis was performed to explore the association between alcohol consumption and increased stomach cancer risk. Eighty-one epidemiology studies, including 68 case-control studies and 13 cohort studies, were included in this study. A significant association was found between alcohol consumption and increased risk of stomach cancer (OR = 1.20, 95% CI 1.12-1.27). To explore the source of the significant heterogeneity (p < 0.05, I = 86%), analysis was stratified by study type (case-control study and cohort study), control type (hospital-based control and population-based control), gender (male, female, and mix), race (White and Asian), region (United States, Sweden, China, Japan), subsite of stomach cancer, and type of alcohol. The stratified analyses found that region and cancer subsite are major sources of the high heterogeneity. The inconsistent results in different regions and different subsites might be related to smoking rates, Helicobacter pylori infection, obesity, and potential genetic susceptibility. The positive association between drinking and increased risk of stomach cancer is consistent in stratified analyses. The dose-response analysis showed a clear trend that a higher daily intake of alcohol is associated with a higher risk of stomach cancer.
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http://dx.doi.org/10.1016/j.cbi.2021.109365DOI Listing
February 2021

Network machine learning maps phytochemically rich "Hyperfoods" to fight COVID-19.

Hum Genomics 2021 01 2;15(1). Epub 2021 Jan 2.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, SW7 2AZ, UK.

In this paper, we introduce a network machine learning method to identify potential bioactive anti-COVID-19 molecules in foods based on their capacity to target the SARS-CoV-2-host gene-gene (protein-protein) interactome. Our analyses were performed using a supercomputing DreamLab App platform, harnessing the idle computational power of thousands of smartphones. Machine learning models were initially calibrated by demonstrating that the proposed method can predict anti-COVID-19 candidates among experimental and clinically approved drugs (5658 in total) targeting COVID-19 interactomics with the balanced classification accuracy of 80-85% in 5-fold cross-validated settings. This identified the most promising drug candidates that can be potentially "repurposed" against COVID-19 including common drugs used to combat cardiovascular and metabolic disorders, such as simvastatin, atorvastatin and metformin. A database of 7694 bioactive food-based molecules was run through the calibrated machine learning algorithm, which identified 52 biologically active molecules, from varied chemical classes, including flavonoids, terpenoids, coumarins and indoles predicted to target SARS-CoV-2-host interactome networks. This in turn was used to construct a "food map" with the theoretical anti-COVID-19 potential of each ingredient estimated based on the diversity and relative levels of candidate compounds with antiviral properties. We expect this in silico predicted food map to play an important role in future clinical studies of precision nutrition interventions against COVID-19 and other viral diseases.
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http://dx.doi.org/10.1186/s40246-020-00297-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775839PMC
January 2021

Impact of COVID-19 pandemic on mental health: An international study.

PLoS One 2020 31;15(12):e0244809. Epub 2020 Dec 31.

Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.

Background: The COVID-19 pandemic triggered vast governmental lockdowns. The impact of these lockdowns on mental health is inadequately understood. On the one hand such drastic changes in daily routines could be detrimental to mental health. On the other hand, it might not be experienced negatively, especially because the entire population was affected.

Methods: The aim of this study was to determine mental health outcomes during pandemic induced lockdowns and to examine known predictors of mental health outcomes. We therefore surveyed n = 9,565 people from 78 countries and 18 languages. Outcomes assessed were stress, depression, affect, and wellbeing. Predictors included country, sociodemographic factors, lockdown characteristics, social factors, and psychological factors.

Results: Results indicated that on average about 10% of the sample was languishing from low levels of mental health and about 50% had only moderate mental health. Importantly, three consistent predictors of mental health emerged: social support, education level, and psychologically flexible (vs. rigid) responding. Poorer outcomes were most strongly predicted by a worsening of finances and not having access to basic supplies.

Conclusions: These results suggest that on whole, respondents were moderately mentally healthy at the time of a population-wide lockdown. The highest level of mental health difficulties were found in approximately 10% of the population. Findings suggest that public health initiatives should target people without social support and those whose finances worsen as a result of the lockdown. Interventions that promote psychological flexibility may mitigate the impact of the pandemic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774914PMC
January 2021

COVID-19 update: the first 6 months of the pandemic.

Hum Genomics 2020 12 23;14(1):48. Epub 2020 Dec 23.

Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, 4878, Australia.

The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.
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http://dx.doi.org/10.1186/s40246-020-00298-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757844PMC
December 2020

Acetaminophen Attenuates invasion and alters the expression of extracellular matrix enzymes and vascular factors in human first trimester trophoblast cells.

Placenta 2021 01 5;104:146-160. Epub 2020 Dec 5.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, 06510, USA; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06510, USA. Electronic address:

Acetaminophen is one of the most common medications taken during pregnancy, considered safe for maternal health and fetal development. However, recent epidemiological studies have associated prenatal acetaminophen use with several developmental disorders in offspring. As acetaminophen can freely cross into and through the placenta, epidemiological associations with prenatal acetaminophen use may reflect direct actions on the fetus and/or the impact of altered placental functions. In the absence of rigorous mechanistic studies, our understanding of how prenatal acetaminophen exposure can cause long-term effects in offspring is limited. The objective of this study was to determine whether acetaminophen can alter key functions of a major placental cell type by utilizing immortalized human first trimester trophoblast cells. This study employed a comparative analysis with the nonsteroidal, anti-inflammatory drug aspirin, which has established effects in first trimester trophoblast cells. We report that immortalized trophoblast cells express the target proteins of acetaminophen and aspirin: cyclooxygenase (COX) -1 and -2. Unlike aspirin, acetaminophen significantly repressed the expression of angiogenesis and vascular remodeling genes in HTR-8/SVneo cells. Moreover, acetaminophen impaired trophoblast invasion by over 80%, while aspirin had no effect on invasion. Acetaminophen exposure reduced the expression of matrix metalloproteinase (MMP)-2 and -9 and increased the expression of tissue inhibitors of matrix metalloproteinases 2, leading to an imbalance in the ratio of proteolytic enzymes. Finally, a bioinformatic approach identified novel acetaminophen-responsive gene networks associated with key trophoblast functions and disease. Together these results suggest that prenatal acetaminophen use may interfere with critical trophoblast functions early in gestation, which may subsequently impact fetal development.
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http://dx.doi.org/10.1016/j.placenta.2020.12.002DOI Listing
January 2021

Bringing Big Data to Bear in Environmental Public Health: Challenges and Recommendations.

Front Artif Intell 2020 May 15;3. Epub 2020 May 15.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, United States.

Understanding the role that the environment plays in influencing public health often involves collecting and studying large, complex data sets. There have been a number of private and public efforts to gather sufficient information and confront significant unknowns in the field of environmental public health, yet there is a persistent and largely unmet need for findable, accessible, interoperable, and reusable (FAIR) data. Even when data are readily available, the ability to create, analyze, and draw conclusions from these data using emerging computational tools, such as augmented and artificial inteligence (AI) and machine learning, requires technical skills not currently implemented on a programmatic level across research hubs and academic institutions. We argue that collaborative efforts in data curation and storage, scientific computing, and training are of paramount importance to empower researchers within environmental sciences and the broader public health community to apply AI approaches and fully realize their potential. Leaders in the field were asked to prioritize challenges in incorporating big data in environmental public health research: inconsistent implementation of FAIR principles in data collection and sharing, a lack of skilled data scientists and appropriate cyber-infrastructures, and limited understanding of possibilities and communication of benefits were among those identified. These issues are discussed, and actionable recommendations are provided.
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http://dx.doi.org/10.3389/frai.2020.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654840PMC
May 2020

Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data.

Nat Biotechnol 2021 02 9;39(2):169-173. Epub 2020 Nov 9.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.
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http://dx.doi.org/10.1038/s41587-020-0700-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971188PMC
February 2021

Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer.

Chem Biol Interact 2020 Nov 29;331:109274. Epub 2020 Sep 29.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06510, United States. Electronic address:

Background: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Mutations in the adenomatous polyposis coli (APC) gene are pivotal in colorectal tumorigenesis. Recently, we demonstrated that aldehyde dehydrogenase 1B1 (ALDH1B1) knockdown dramatically reduced colon tumor growth in a mouse xenograft model. The purpose of the present preliminary study is to examine the effect of loss of ALDH1B1 in CRC development in an inducible colon-specific Apc mouse model.

Methods: ApcCdx2 mice develop uni-allelic inactivation of Apc specifically in colon epithelial cells following tamoxifen treatment. Aldh1b1 KO mice were crossed with ApcCdx2 mice. Six-month-old male ApcCdx2/Aldh1b1, and ApcCdx2/Aldh1b1 mice were treated with tamoxifen (50 mg/kg, i.p.) for three consecutive days. Apc/Aldh1b1 and Apc/Aldh1b1 mice were treated with corn oil (i.e., tamoxifen vehicle control) for three consecutive days. Eighteen days later, mice were sacrificed and their colons examined microscopically, macroscopically and histologically for the presence of adenoma.

Results: All ApcCdx2/Aldh1b1 and ApcCdx2/Aldh1b1 mice treated with tamoxifen developed colorectal adenoma. The ApcCdx2/Aldh1b1 mice showed a significant decrease in the total volume of all ileal and colonic adenomas, and decreased incidence of large colonic adenoma compared to ApcCdx2/Aldh1b1 mice. Immunohistochemical analysis of p53 and β-catenin showed a trend toward decreased expression score in colonic adenomas of ApcCdx2/Aldh1b1 mice.

Conclusion: The present preliminary study suggests that deletion of ALDH1B1 may protect against the full development of colorectal cancer. Further mechanistic studies are required to elucidate how ALDH1B1 contributes for colorectal cancer.
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http://dx.doi.org/10.1016/j.cbi.2020.109274DOI Listing
November 2020

A Digital Substance-Use Harm Reduction Intervention for Students in Higher Education (MyUSE): Protocol for Project Development.

JMIR Res Protoc 2020 Aug 27;9(8):e17829. Epub 2020 Aug 27.

Student Health Department, University College Cork, Cork, Ireland.

Background: Digital interventions have been identified as a possible tool for reducing the harm caused by illicit drug use among students attending higher education (ie, college students). However, the success of interventions in this area has been hampered by a lack of user involvement and behavior change theory in their design. The My Understanding of Substance use Experiences (MyUSE) project combines a rigorous user-centered design (UCD) methodology and a robust behavioral change framework to develop a digitally delivered harm reduction intervention for illicit drug use among students in higher education.

Objective: This project aims to design and develop a digital intervention that targets drug use-related harm among students in higher education.

Methods: The MyUSE project will take place over 3 phases. The first phase was exploratory in nature, involving 3 systematic reviews, a large survey, and student workshops to gather a comprehensive evidence base to guide the project. The second phase is the development stage of the project, involving the use of the Behavior Change Wheel theoretical framework to determine the behavior change techniques of the intervention and the use of the UCD methodology to guide the development of the digital intervention. The third phase is the evaluation stage, whereby the intervention will undergo a 5-stage evaluation process to comprehensively evaluate its impacts.

Results: The exploratory phase 1 of the MyUSE project was completed in December 2018. Phase 2 is currently underway, and phase 3 is due to begin in September 2020.

Conclusions: Higher education institutions (HEIs) are ideally placed to intervene and support students in the area of illicit drug use but are constrained by limited resources. Current digital interventions in this area are sparse and have several weaknesses. The MyUSE project combines a UCD approach with a robust behavior change framework to develop a digitally delivered intervention that is economically viable, effective in changing behavior, usable and acceptable to students, and able to sustain long-term implementation in HEIs.

International Registered Report Identifier (irrid): DERR1-10.2196/17829.
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http://dx.doi.org/10.2196/17829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484779PMC
August 2020

Toward Comprehensive Per- and Polyfluoroalkyl Substances Annotation Using FluoroMatch Software and Intelligent High-Resolution Tandem Mass Spectrometry Acquisition.

Anal Chem 2020 08 6;92(16):11186-11194. Epub 2020 Aug 6.

Center for Environmental and Human Toxicology & Department of Physiological Sciences, University of Florida, Gainesville, Florida 32611, United States.

Thousands of per- and polyfluoroalkyl substances (PFAS) exist in the environment and pose a potential health hazard. Suspect and nontarget screening with liquid chromatography (LC)-high-resolution tandem mass spectrometry (HRMS/MS) can be used for comprehensive characterization of PFAS. To date, no automated open source PFAS data analysis software exists to mine these extensive data sets. We introduce FluoroMatch, which automates file conversion, chromatographic peak picking, blank feature filtering, PFAS annotation based on precursor and fragment masses, and annotation ranking. The software library currently contains ∼7 000 PFAS fragmentation patterns based on rules derived from standards and literature, and the software automates a process for users to add additional compounds. The use of intelligent data-acquisition methods (iterative exclusion) nearly doubled the number of annotations. The software application is demonstrated by characterizing PFAS in landfill leachate as well as in leachate foam generated to concentrate the compounds for remediation purposes. FluoroMatch had wide coverage, returning 27 PFAS annotations for landfill leachate samples, explaining 71% of the all-ion fragmentation (CF) related fragments. By improving the throughput and coverage of PFAS annotation, FluoroMatch will accelerate the discovery of PFAS posing significant human risk.
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http://dx.doi.org/10.1021/acs.analchem.0c01591DOI Listing
August 2020

Overview of PAX gene family: analysis of human tissue-specific variant expression and involvement in human disease.

Hum Genet 2021 Mar 29;140(3):381-400. Epub 2020 Jul 29.

Department of Environmental Health Sciences, Yale School of Public Health, 60 College Street, New Haven, CT, 06510, USA.

Paired-box (PAX) genes encode a family of highly conserved transcription factors found in vertebrates and invertebrates. PAX proteins are defined by the presence of a paired domain that is evolutionarily conserved across phylogenies. Inclusion of a homeodomain and/or an octapeptide linker subdivides PAX proteins into four groups. Often termed "master regulators", PAX proteins orchestrate tissue and organ development throughout cell differentiation and lineage determination, and are essential for tissue structure and function through maintenance of cell identity. Mutations in PAX genes are associated with myriad human diseases (e.g., microphthalmia, anophthalmia, coloboma, hypothyroidism, acute lymphoblastic leukemia). Transcriptional regulation by PAX proteins is, in part, modulated by expression of alternatively spliced transcripts. Herein, we provide a genomics update on the nine human PAX family members and PAX homologs in 16 additional species. We also present a comprehensive summary of human tissue-specific PAX transcript variant expression and describe potential functional significance of PAX isoforms. While the functional roles of PAX proteins in developmental diseases and cancer are well characterized, much remains to be understood regarding the functional roles of PAX isoforms in human health. We anticipate the analysis of tissue-specific PAX transcript variant expression presented herein can serve as a starting point for such research endeavors.
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http://dx.doi.org/10.1007/s00439-020-02212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939107PMC
March 2021

Acceptance and Commitment Therapy for Primary Headache Sufferers: A Randomized Controlled Trial of Efficacy.

J Pain 2021 02 17;22(2):143-160. Epub 2020 Jul 17.

Department of Psychology, ACThealthy Laboratory, University of Cyprus, Nicosia, Cyprus. Electronic address:

Prevention of headaches via avoidance of triggers remains the main behavioral treatment suggestion for headache management despite trigger avoidance resulting in increases in potency, lifestyle restrictions, internal locus of control decreases, pain exacerbation and maintenance. New approaches, such as Acceptance and Commitment Therapy (ACT), instead emphasize acceptance and valued living as alternatives to avoidance. Though ACT is an empirically supported treatment for chronic pain, there is limited evidence for headache management while preliminary outcome studies are afflicted with methodological limitations. This study compared an ACT-based group headache-specific intervention to wait-list control, in a randomized clinical trial, on disability, distress, medical utilization, functioning, and quality of life. Ninety-four individuals with primary headache (84% women; Mage = 43 years; 87.35% migraine diagnosis) were randomized into 2 groups (47 in each). Assessments occurred: before, immediately after, and at 3 months following treatment end. Only the ACT group was additionally assessed at 6- and 12-month follow-up. Results (intent to treat analyses corroborated by linear mixed model analyses) showed substantial improvements in favor of ACT compared to control, on disability, quality of life, functional status, and depression at 3-, 6-, and 12-month follow-up. Improvements were maintained in the ACT group at 6- and 12-month follow-up. At 3-month follow-up, clinical improvement occurred in headache-related disability (63%) and 65% in quality of life in ACT versus 37% and 35% in control. These findings offer new evidence for the utility and efficacy of ACT in localized pain conditions and yields evidence for both statistical and clinical improvements over a years' period. PERSPECTIVE: An Acceptance and Commitment Therapy approach focusing on acceptance and values-based activities was found to improve disability, functioning, and quality of life among patients with primary headaches.
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http://dx.doi.org/10.1016/j.jpain.2020.06.006DOI Listing
February 2021

Genomics of COVID-19: molecular mechanisms going from susceptibility to severity of the disease.

Hum Genomics 2020 06 10;14(1):22. Epub 2020 Jun 10.

Australia Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, Australia.

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http://dx.doi.org/10.1186/s40246-020-00273-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283035PMC
June 2020

COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission.

Hum Genomics 2020 05 12;14(1):17. Epub 2020 May 12.

Department of Environmental Health Sciences, School of Public Health, Yale University, New Haven, CT, 06510, USA.

The recent coronavirus disease (COVID-19), caused by SARS-CoV-2, is inarguably the most challenging coronavirus outbreak relative to the previous outbreaks involving SARS-CoV and MERS-CoV. With the number of COVID-19 cases now exceeding 2 million worldwide, it is apparent that (i) transmission of SARS-CoV-2 is very high and (ii) there are large variations in disease severity, one component of which may be genetic variability in the response to the virus. Controlling current rates of infection and combating future waves require a better understanding of the routes of exposure to SARS-CoV-2 and the underlying genomic susceptibility to this disease. In this mini-review, we highlight possible genetic determinants of COVID-19 and the contribution of aerosol exposure as a potentially important transmission route of SARS-CoV-2.
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http://dx.doi.org/10.1186/s40246-020-00267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214856PMC
May 2020

Summary of the 2019 alcohol and immunology research interest group (AIRIG) meeting: Alcohol-mediated mechanisms of multiple organ injury.

Alcohol 2020 09 28;87:89-95. Epub 2020 Apr 28.

Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA; Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA; Immunology Graduate Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

On November 15, 2019, the 24th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Society for Leukocyte Biology meeting in Boston, Massachusetts. The 2019 meeting focused on alcohol, immunity, and organ damage, and included two plenary sessions. The first session highlighted new research exploring the mechanisms of alcohol-induced inflammation and liver disease, including effects on lipidomics and lipophagy, regulatory T cells, epigenetics, epithelial cells, and age-related changes in the gut. The second session covered alcohol-induced injury of other organs, encompassing diverse areas of research ranging from neurodegeneration, to lung barrier function, to colon carcinogenesis, to effects on viral infection. The discussions also highlighted current laboratory and clinical research used to identify biomarkers of alcohol use and disease.
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http://dx.doi.org/10.1016/j.alcohol.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483664PMC
September 2020

Environmental lipidomics: understanding the response of organisms and ecosystems to a changing world.

Metabolomics 2020 04 19;16(5):56. Epub 2020 Apr 19.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, 1333 Center Drive, Gainesville, FL, 32610, USA.

Background: Understanding the interaction between organisms and the environment is important for predicting and mitigating the effects of global phenomena such as climate change, and the fate, transport, and health effects of anthropogenic pollutants. By understanding organism and ecosystem responses to environmental stressors at the molecular level, mechanisms of toxicity and adaptation can be determined. This information has important implications in human and environmental health, engineering biotechnologies, and understanding the interaction between anthropogenic induced changes and the biosphere. One class of molecules with unique promise for environmental science are lipids; lipids are highly abundant and ubiquitous across nearly all organisms, and lipid profiles often change drastically in response to external stimuli. These changes allow organisms to maintain essential biological functions, for example, membrane fluidity, as they adapt to a changing climate and chemical environment. Lipidomics can help scientists understand the historical and present biofeedback processes in climate change and the biogeochemical processes affecting nutrient cycles. Lipids can also be used to understand how ecosystems respond to historical environmental changes with lipid signatures dating back to hundreds of millions of years, which can help predict similar changes in the future. In addition, lipids are direct targets of environmental stressors, for example, lipids are easily prone to oxidative damage, which occurs during exposure to most toxins.

Aim Of Review: This is the first review to summarize the current efforts to comprehensively measure lipids to better understand the interaction between organisms and their environment. This review focuses on lipidomic applications in the arenas of environmental toxicology and exposure assessment, xenobiotic exposures and health (e.g., obesity), global climate change, and nutrient cycles. Moreover, this review summarizes the use of and the potential for lipidomics in engineering biotechnologies for the remediation of persistent compounds and biofuel production.

Key Scientific Concept: With the preservation of certain lipids across millions of years and our ever-increasing understanding of their diverse biological roles, lipidomic-based approaches provide a unique utility to increase our understanding of the contemporary and historical interactions between organisms, ecosystems, and anthropogenically-induced environmental changes.
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http://dx.doi.org/10.1007/s11306-020-01665-3DOI Listing
April 2020

Zinc Levels and Birth Weight in Pregnant Women with Gestational Diabetes Mellitus: A Matched Cohort Study in China.

J Clin Endocrinol Metab 2020 07;105(7)

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.

Background: Zinc (Zn) has been suggested to impact fetal growth. However, the effect may be complicated by gestational diabetes mellitus (GDM) due to its impact on fetal growth and placental transport. This study aims to investigate whether GDM modifies the association between Zn levels and birth weight.

Method: A cohort matched by GDM was established in Taiyuan, China, between 2012 and 2016, including 752 women with GDM and 744 women without. Dietary Zn intake was assessed during pregnancy. Maternal blood (MB) and cord blood (CB) Zn levels were measured at birth. Birth weight was standardized as the z score and categorized as high (HBW, >4000 g) and low (LBW, <2500 g) groups. Multivariate linear regression and multinomial logistic regression were used to examine the association between Zn levels and birth weight in offspring born to women with or without GDM.

Results: 88.8% (N = 1328) of the population had inadequate Zn intake during pregnancy. In women with GDM, MB Zn level was inversely associated with birth weight (β = -.17; 95% confidence interval (CI), -0.34 to -0.01), while CB Zn level was positively associated with birth weight (β = .38; 95% CI, 0.06-0.70); suggestive associations were observed between MB Zn level and LBW (odds ratio 2.01; 95% CI, 0.95-4.24) and between CB Zn level and HBW (odds ratio 2.37; 95% CI, 1.08-5.21).

Conclusions: GDM may modify the associations between MB and CB Zn levels and birth weight in this population characterized by insufficient Zn intake. These findings suggest a previously unidentified path of adverse effects of GDM.
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http://dx.doi.org/10.1210/clinem/dgaa171DOI Listing
July 2020

Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function.

Cell Metab 2020 05 25;31(5):920-936.e7. Epub 2020 Mar 25.

Cancer Metabolism Group, Department of Oncology, 84 Val Fleuri, Luxembourg, Luxembourg.

Regulatory T cells (Tregs) maintain immune homeostasis and prevent autoimmunity. Serine stimulates glutathione (GSH) synthesis and feeds into the one-carbon metabolic network (1CMet) essential for effector T cell (Teff) responses. However, serine's functions, linkage to GSH, and role in stress responses in Tregs are unknown. Here, we show, using mice with Treg-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that GSH loss in Tregs alters serine import and synthesis and that the integrity of this feedback loop is critical for Treg suppressive capacity. Although Gclc ablation does not impair Treg differentiation, mutant mice exhibit severe autoimmunity and enhanced anti-tumor responses. Gclc-deficient Tregs show increased serine metabolism, mTOR activation, and proliferation but downregulated FoxP3. Limitation of cellular serine in vitro and in vivo restores FoxP3 expression and suppressive capacity of Gclc-deficient Tregs. Our work reveals an unexpected role for GSH in restricting serine availability to preserve Treg functionality.
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http://dx.doi.org/10.1016/j.cmet.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265172PMC
May 2020

Lipid Annotator: Towards Accurate Annotation in Non-Targeted Liquid Chromatography High-Resolution Tandem Mass Spectrometry (LC-HRMS/MS) Lipidomics Using A Rapid and User-Friendly Software.

Metabolites 2020 Mar 12;10(3). Epub 2020 Mar 12.

Agilent Technologies, 95051 Santa Clara, CA, USA.

Lipidomics has great promise in various applications; however, a major bottleneck in lipidomics is the accurate and comprehensive annotation of high-resolution tandem mass spectral data. While the number of available lipidomics software has drastically increased over the past five years, the reduction of false positives and the realization of obtaining structurally accurate annotations remains a significant challenge. We introduce Lipid Annotator, which is a user-friendly software for lipidomic analysis of data collected by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). We validate annotation accuracy against lipid standards and other lipidomics software. Lipid Annotator was integrated into a workflow applying an iterative exclusion MS/MS acquisition strategy to National Institute of Standards and Technology (NIST) SRM 1950 Metabolites in Frozen Human Plasma using reverse phase LC-HRMS/MS. Lipid Annotator, LipidMatch, and MS-DIAL produced consensus annotations at the level of lipid class for 98% and 96% of features detected in positive and negative mode, respectively. Lipid Annotator provides percentages of fatty acyl constituent species and employs scoring algorithms based on probability theory, which is less subjective than the tolerance and weighted match scores commonly used by available software. Lipid Annotator enables analysis of large sample cohorts and improves data-processing throughput as compared to previous lipidomics software.
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http://dx.doi.org/10.3390/metabo10030101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142889PMC
March 2020