Effectiveness and minimum effective dose of app-based mobile health interventions for anxiety and depression symptom reduction: Systematic review and meta-analysis

BACKGROUND: Mobile health (mHealth) apps offer new opportunities to deliver psychological treatments for mental illness in an accessible, private format. The results of several previous systematic reviews support the use of app-based mHealth interventions for anxiety and depression symptom management. However, it remains unclear how much or how long the minimum treatment dose is for an mHealth intervention to be effective. Just-in-time adaptive intervention (JITAI) has been introduced in the mHealth domain to facilitate behavior changes and is positioned to guide the design of mHealth interventions with enhanced adherence and effectiveness. OBJECTIVE: Inspired by the JITAI framework, we conducted a systematic review and meta-analysis to evaluate the dose effectiveness of app-based mHealth interventions for anxiety and depression symptom reduction. METHODS: We conducted a literature search on 7 databases (ie, Ovid MEDLINE, Embase, PsycInfo, Scopus, Cochrane Library (eg, CENTRAL), ScienceDirect, and ClinicalTrials, for publications from January 2012 to April 2020. We included randomized controlled trials (RCTs) evaluating app-based mHealth interventions for anxiety and depression. The study selection and data extraction process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We estimated the pooled effect size using Hedge g and appraised study quality using the revised Cochrane risk-of-bias tool for RCTs. RESULTS: We included 15 studies involving 2627 participants for 18 app-based mHealth interventions. Participants in the intervention groups showed a significant effect on anxiety (Hedge g=-.10, 95% CI -0.14 to -0.06, I2=0%) but not on depression (Hedge g=-.08, 95% CI -0.23 to 0.07, I2=4%). Interventions of at least 7 weeks\u27 duration had larger effect sizes on anxiety symptom reduction. CONCLUSIONS: There is inconclusive evidence for clinical use of app-based mHealth interventions for anxiety and depression at the current stage due to the small to nonsignificant effects of the interventions and study quality concerns. The recommended dose of mHealth interventions and the sustainability of intervention effectiveness remain unclear and require further investigation

PhenDisco: phenotype discovery system for the database of genotypes and phenotypes.

The database of genotypes and phenotypes (dbGaP) developed by the National Center for Biotechnology Information (NCBI) is a resource that contains information on various genome-wide association studies (GWAS) and is currently available via NCBI's dbGaP Entrez interface. The database is an important resource, providing GWAS data that can be used for new exploratory research or cross-study validation by authorized users. However, finding studies relevant to a particular phenotype of interest is challenging, as phenotype information is presented in a non-standardized way. To address this issue, we developed PhenDisco (phenotype discoverer), a new information retrieval system for dbGaP. PhenDisco consists of two main components: (1) text processing tools that standardize phenotype variables and study metadata, and (2) information retrieval tools that support queries from users and return ranked results. In a preliminary comparison involving 18 search scenarios, PhenDisco showed promising performance for both unranked and ranked search comparisons with dbGaP's search engine Entrez. The system can be accessed at http://pfindr.net

Asynchrony of Gambierdiscus spp. abundance and toxicity in the U.S. Virgin Islands: implications for monitoring and management of Ciguatera

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Liefer, J. D., Richlen, M. L., Smith, T. B., DeBose, J. L., Xu, Y., Anderson, D. M., & Robertson, A. Asynchrony of Gambierdiscus spp. abundance and toxicity in the U.S. Virgin Islands: implications for monitoring and management of Ciguatera. Toxins, 13(6), (2021): 413, https://doi.org/10.3390/toxins13060413.Ciguatera poisoning (CP) poses a significant threat to ecosystem services and fishery resources in coastal communities. The CP-causative ciguatoxins (CTXs) are produced by benthic dinoflagellates including Gambierdiscus and Fukuyoa spp., and enter reef food webs via grazing on macroalgal substrates. In this study, we report on a 3-year monthly time series in St. Thomas, US Virgin Islands where Gambierdiscus spp. abundance and Caribbean-CTX toxicity in benthic samples were compared to key environmental factors, including temperature, salinity, nutrients, benthic cover, and physical data. We found that peak Gambierdiscus abundance occurred in summer while CTX-specific toxicity peaked in cooler months (February–May) when the mean water temperatures were approximately 26–28 °C. These trends were most evident at deeper offshore sites where macroalgal cover was highest year-round. Other environmental parameters were not correlated with the CTX variability observed over time. The asynchrony between Gambierdiscus spp. abundance and toxicity reflects potential differences in toxin cell quotas among Gambierdiscus species with concomitant variability in their abundances throughout the year. These results have significant implications for monitoring and management of benthic harmful algal blooms and highlights potential seasonal and highly-localized pulses in reef toxin loads that may be transferred to higher trophic levels.This work was funded in part by the National Oceanic and Atmospheric Administration, Ecology and Oceanography of Harmful Algal Blooms Program (ECOHAB publication number 984) through the CiguaHAB project (NA11NOS4780028), and also contributes to CIGUATOX (NA17NOS4780181) granted to coauthors AR, TBS, DMA, and MLR. Additional support was provided by NSF Partnerships in International Research and Education (1743802), and the Greater Caribbean Center for Ciguatera Research (NIH 1P01ES028949-01 and NSF 1841811). Financial support of YX was from the National Natural Science Foundation of China (41976155), the Natural Science Foundation of Guangxi Province (2020GXNSFDA297001)

LSU rDNA based RFLP assays for the routine identification of Gambierdiscus species

© The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Harmful Algae 66 (2017): 20-28, doi:10.1016/j.hal.2017.04.009.Gambierdiscus is a genus of benthic dinoflagellates commonly associated with ciguatera fish poisoning (CFP), which is generally found in tropical or sub-tropical regions around the world. Morphologically similar species within the genus can vary in toxicity; however, species identifications are difficult or sometimes impossible using light microscopy. DNA sequencing of ribosomal RNA genes (rDNA) is thus often used to identify and describe Gambierdiscus species and ribotypes, but the expense and time can be prohibitive for routine culture screening and/or large-scale monitoring programs. This study describes a restriction fragment length polymorphism (RFLP) typing method based on analysis of the large subunit ribosomal RNA gene (rDNA) that can successfully identify at least nine of the described Gambierdiscus species and two Fukuyoa species. The software programs DNAMAN 6.0 and Restriction Enzyme Picker were used to identify a set of restriction enzymes (SpeI, HpyCH4IV, and TaqαI) capable of distinguishing most of the known Gambierdiscus species for which DNA sequences were available. This assay was tested using in silico analysis and cultured isolates, and species identifications of isolates assigned by RFLP typing were confirmed by DNA sequencing. To verify the assay and assess intra-specific heterogeneity in RFLP patterns, identifications of 63 Gambierdiscus isolates comprising ten Gambierdiscus species, one ribotype, and two Fukuyoa species were confirmed using RFLP typing, and this method was subsequently employed in the routine identification of isolates collected from the Caribbean Sea. The RFLP assay presented here reduces the time and cost associated with morphological identification via scanning electron microscopy and/or DNA sequencing, and provides a phylogenetically sensitive method for routine Gambierdiscus species assignment.Funding for this study was provided by the U.S. National Oceanic and Atmospheric Administration ECOHAB program (CiguaHAB; Cooperative Agreement NA11NOS4780060, NA11NOS4780028), the China Scholarship Council and Natural Science Foundation of China (No. 41606137, 41606136), and the Guangxi Natural Science Foundation (2015GXNSFCA139003, 2016GXNSFBA380037)

Distribution, abundance and diversity of Gambierdiscus spp. from a ciguatera endemic area in Marakei, Republic of Kiribati

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Harmful Algae 34 (2014): 56–68, doi:10.1016/j.hal.2014.02.007.Ciguatera is a serious seafood poisoning syndrome caused by the consumption of ciguatoxin-contaminated finfish from tropical and subtropical regions. This study examined the community structure of ciguatera-associated dinoflagellates and the distribution pattern, taxonomy and toxicity of Gambierdiscus spp. from a high-risk area of Marakei, Republic of Kiribati. The genera Gambierdiscus, Prorocentrum, Ostreopsis, Amphidinium and Coolia were present, and generally the former three dominated the dinoflagellate assemblage. Among these three, Gambierdiscus was the most abundant dinoflagellate genus observed at three of the four sites sampled, two of which (Sites 1 and 2) were on the northern half of the island and two (Sites 3 and 4) on the southern half. The following patterns of abundance were observed among sites: (1) Average Gambierdiscus spp. abundance at the northern sites exceeded the southern sites by a factor of 19-54; and (2) Gambierdiscus spp. abundance at shallow sites (2-3 m) exceeded deeper sites (10-15 m). The distribution of Gambierdiscus spp. at Marakei corresponded with previously observed patterns of fish toxicity, with fish from southern locations being much less toxic than fish sampled north of the central channel. DNA sequencing identified three Gambierdiscus species (G. carpenteri, G. belizeanus, G. pacificus) and three previously unreported ribotypes (Gambierdiscus sp. type 4, Gambierdiscus sp. type 5, Gambierdiscus sp. type 6) in the samples; Gambierdiscus sp. type 4 may represent a Pacific clade of Gambierdiscus sp. ribotype 1. Toxicity analyses determined that Gambierdiscus sp. type 4 isolates were more toxic than the Gambierdiscus sp. type 5 and G. pacificus isolates, with toxin contents of 2.6-6.0 (mean: 4.3± 1.4), 0.010 and 0.011 fg P-CTX-1 eq cell-1, respectively. Despite low densities of Gambierdiscus spp. observed at Marakei relative to other studies in other parts of the world, the presence of low and moderately toxic populations may be sufficient to render the western coast of Marakei a high-risk area for ciguatera. The long history of toxicity along the western side of Marakei suggests that large-scale oceanographic forcings that regulate the distribution of Gambierdiscus spp. along the western side of Marakei may have remained relatively stable over that time. Chronic as well as acute exposure to ciguatoxins may therefore pose an important human health impact to the residents of Marakei.Funding for this work was provided by the Centers for Disease Control and Prevention (U01 EH000421), USFDA (F223201000060C), NOAA NOS (Cooperative Agreement NA11NOS4780060, NA11NOS4780028), National Program on Key Basic Research Project of China (973 Program, 2013CB956503), the Nonprofit Research Project for the State Oceanic Administration (China, 201005006-01), and the National Natural Science Foundation of China (41276110)

Epigenome-Wide Association Study of Kidney Function Identifies Trans-Ethnic and Ethnic-Specific Loci

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context

ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development

To determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metabolic reprogramming and induced stronger inflammation in AA than in TA; 2) Ang II and HFD upregulated 890 genes in AA versus TA and induced cytokine signaling; 3) Ang II AA and TA upregulated 73 and 68 cytokines, scRNA-Seq identified markers of macrophages and immune cells, cell death regulators, respectively; transdifferentiation markers of neuron, glial, and squamous epithelial cells were upregulated by Ang II-AA and TA; and pyroptosis signaling with IL-1β and caspase-4 were more upregulated in Ang II-AA than in TA; 4) Six upregulated transcriptomes in patients with AAA, Ang II AA, Ang II TA, additional aneurysm models, PPE-AAA and BAPN-Ang II-AAA, were partially overlapped with 10 lists of new ER stress gene sets including 3 interaction protein lists of ER stress regulators ATF6, PERK, and IRE1, HPA ER localization genes, KEGG signal genes, XBP1 transcription targets, ATF4 (PERK) targets, ATF6 targets, thapsigargin ER stress genes, tunicamycin-ER stress genes, respectively; 5) Ang II-AA and TA upregulated ROS regulators, MitoCarta genes, trained immunity genes, and glycolysis genes; and 6) Gene KO transcriptomes indicated that ATF6 and PERK played more significant roles than IRE1 in promoting AAA and trained immunity whereas antioxidant NRF2 inhibited them. Our unprecedented ER-focused transcriptomic analyses have provided novel insights on the roles of ER as an immune organelle in sensing various DAMPs and initiating ER stress that triggers Ang II-accelerated trained immunity and differs susceptibilities of thoracic and abdominal aortas to diseases

Innate immunity of vascular smooth muscle cells contributes to two-wave inflammation in atherosclerosis, twin-peak inflammation in aortic aneurysms and trans-differentiation potential into 25 cell types

IntroductionVascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in aortic diseases. Innate immunity is the main driving force for cardiovascular diseases. MethodsTo determine the roles of innate immunity in VSMC and aortic pathologies, we performed transcriptome analyses on aortas from ApoE–/– angiotensin II (Ang II)-induced aortic aneurysm (AAA) time course, and ApoE–/– atherosclerosis time course, as well as VSMCs stimulated with danger-associated molecular patterns (DAMPs).ResultsWe made significant findings: 1) 95% and 45% of the upregulated innate immune pathways (UIIPs, based on data of 1226 innate immune genes) in ApoE–/– Ang II-induced AAA at 7 days were different from that of 14 and 28 days, respectively; and AAA showed twin peaks of UIIPs with a major peak at 7 days and a minor peak at 28 days; 2) all the UIIPs in ApoE–/– atherosclerosis at 6 weeks were different from that of 32 and 78 weeks (two waves); 3) analyses of additional 12 lists of innate immune-related genes with 1325 cytokine and chemokine genes, 2022 plasma membrane protein genes, 373 clusters of differentiation (CD) marker genes, 280 nuclear membrane protein genes, 1425 nucleoli protein genes, 6750 nucleoplasm protein genes, 1496 transcription factors (TFs) including 15 pioneer TFs, 164 histone modification enzymes, 102 oxidative cell death genes, 68 necrotic cell death genes, and 47 efferocytosis genes confirmed two-wave inflammation in atherosclerosis and twin-peak inflammation in AAA; 4) DAMPs-stimulated VSMCs were innate immune cells as judged by the upregulation of innate immune genes and genes from 12 additional lists; 5) DAMPs-stimulated VSMCs increased trans-differentiation potential by upregulating not only some of 82 markers of 7 VSMC-plastic cell types, including fibroblast, osteogenic, myofibroblast, macrophage, adipocyte, foam cell, and mesenchymal cell, but also 18 new cell types (out of 79 human cell types with 8065 cell markers); 6) analysis of gene deficient transcriptomes indicated that the antioxidant transcription factor NRF2 suppresses, however, the other five inflammatory transcription factors and master regulators, including AHR, NF-KB, NOX (ROS enzyme), PERK, and SET7 promote the upregulation of twelve lists of innate immune genes in atherosclerosis, AAA, and DAMP-stimulated VSMCs; and 7) both SET7 and trained tolerance-promoting metabolite itaconate contributed to twin-peak upregulation of cytokines in AAA. DiscussionOur findings have provided novel insights on the roles of innate immune responses and nuclear stresses in the development of AAA, atherosclerosis, and VSMC immunology and provided novel therapeutic targets for treating those significant cardiovascular and cerebrovascular diseases

Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci

Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context