Publications by authors named "David Gibbs"

83 Publications

Incorporating adaptation and resilience into an integrated watershed and coral reef management plan.

PLoS One 2021 24;16(6):e0253343. Epub 2021 Jun 24.

Patricia Bradley, Tetra Tech, Inc., Owings Mills, MD, United States of America.

Changing environmental conditions are forcing natural resource managers and communities to adapt their strategies to account for global shifts in precipitation, temperature, sea level and more, all of which are occurring in addition to local human impacts. Adapting to threats from climate change requires a fundamental shift in the practice of natural resource management through the development of forward-looking "climate-smart" goals and strategies. Here we present a proof-of-concept application of a decision-support tool to help design climate-smart management actions for the watershed and coral reef management plan for Guánica Bay watershed in southwest Puerto Rico. We also explore the connection between adaptation planning and coral reef resilience, using a recently developed Puerto Rico-wide reef resilience assessment. In the first phase of the study, we used the publicly available Adaptation Design Tool to draft initial climate-smart versions of twelve proposed management actions. In the second phase, two actions (dirt road management on steep slopes, and coral reef restoration) were further refined through consultations with local experts to make more detailed design adjustments; this included the option to use information from the coral reef resilience assessment to inform design improvements. The first phase resulted in moderately detailed assessments that broadly accounted for anticipated direct and indirect effects of climate change on the planned management actions. The second phase resulted in more site-specific technical assessments and additional important design details. The expert panel charged with discussing climate-smart reef restoration around Guánica used the reef resilience assessment to guide discussion of reef restoration, highlighting the importance of having such information available for adaptation planning. This study demonstrates how climate change impacts can be effectively incorporated into a management plan at the most granular level of planning and how a structured, formalized process can be as valuable as the resulting adaptation information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253343PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224911PMC
June 2021

Analysis of Unintentional Falls in Pediatric Population and Predictors of Morbidity.

J Surg Res 2021 Jun 12;267:48-55. Epub 2021 Jun 12.

Division of Pediatric Surgery, Children's Hospital of Orange County, Orange, California.

Introduction: Unintentional falls are a leading cause of pediatric traumatic injury. This study evaluates clinical outcomes of fall-related injuries in children under the age of 10.

Methods: The National Trauma Database was queried for children who experienced an unintentional fall. Patients were stratified by age in two groups: 1-5 and 6-10 years old. The primary outcome was post discharge extension of care, defined as transfer to skilled nursing facility or rehabilitation center after discharge from the hospital. Descriptive statistics and a multivariable logistic regression analysis were used to compare the two groups.

Results: From 2009 to 2016, a total of 8,277 pediatric patients experienced an unintentional fall, with 93.6% of patients being discharged home. Falls were more common in younger children, with greater odds of post discharge extension of care. Predictors of increased associated risk of extended medical care included intracranial hemorrhage (OR 1.05, 95% CI 1.03-1.06) and thoracic injuries (OR 1.03, 95% CI 1.00-1.1.05) (P< 0.05). Mortality in pediatric patients suffering unintentional falls was a rare event occurring in 0.7% of cases in children 1-5 years old and 0.4% of children 6-10 years old.

Conclusion: The majority of children experiencing an unintentional fall are discharged home, with mortality being very rare. However, younger age is prone to more severe and serious injury patterns. Intracranial hemorrhage and thoracic injury were a predictor of need for extended medical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2021.04.036DOI Listing
June 2021

PRoBE the cloud toolkit: finding the best biomarkers of drug response within a breast cancer clinical trial.

JAMIA Open 2021 Apr 3;4(2):ooab038. Epub 2021 Jun 3.

Department of Surgery, University of California San Francisco, San Francisco, California, USA.

Objectives: In this paper, we discuss leveraging cloud-based platforms to collect, visualize, analyze, and share data in the context of a clinical trial. Our cloud-based infrastructure, Patient Repository of Biomolecular Entities (PRoBE), has given us the opportunity for uniform data structure, more efficient analysis of valuable data, and increased collaboration between researchers.

Materials And Methods: We utilize a multi-cloud platform to manage and analyze data generated from the clinical Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2 (I-SPY 2 TRIAL). A collaboration with the Institute for Systems Biology Cancer Gateway in the Cloud has additionally given us access to public genomic databases. Applications to I-SPY 2 data have been built using R Shiny, while leveraging Google's BigQuery tables and SQL commands for data mining.

Results: We highlight the implementation of PRoBE in several unique case studies including prediction of biomarkers associated with clinical response, access to the Pan-Cancer Atlas, and integrating pathology images within the cloud. Our data integration pipelines, documentation, and all codebase will be placed in a Github repository.

Discussion And Conclusion: We are hoping to develop risk stratification diagnostics by integrating additional molecular, magnetic resonance imaging, and pathology markers into PRoBE to better predict drug response. A robust cloud infrastructure and tool set can help integrate these large datasets to make valuable predictions of response to multiple agents. For that reason, we are continuously improving PRoBE to advance the way data is stored, accessed, and analyzed in the I-SPY 2 clinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamiaopen/ooab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172495PMC
April 2021

COVID-19: Differences in sentinel injury and child abuse reporting during a pandemic.

Child Abuse Negl 2021 06 8;116(Pt 2):104990. Epub 2021 Mar 8.

Children's Health of Orange County, Orange, CA, United States; Emergency Department, University of California, Irvine, United States. Electronic address:

Background And Objectives: There is widespread concern that the COVID-19 pandemic has increased the incidence of child maltreatment. However, reports in the scientific literature documenting rates of child maltreatment during this period are scarce. This study was designed to explore whether the incidence of child maltreatment among patients presenting to a pediatric emergency department has increased during the COVID-19 pandemic.

Methods: We conducted a retrospective review of patients of all ages presenting to a pediatric Emergency Department trauma center, who also had a child abuse report filing or a sentinel injury diagnosis related to their index visit. All such patients who presented to this institution from March through July of 2017 through 2020 were included in the study.

Results: Analysis demonstrated an increase in the incidence of child maltreatment in May and June of 2020 and that there was an overall shift in distribution of types of child maltreatment during the COVID-19 pandemic. There was a significant increase in the proportion of emotional/psychological abuse (2.52 % before the pandemic to 7.00 % during the pandemic, p ≤ 0.0001) and non-medical neglect (31.5%-40.0%, p ≤ 0.0001).

Conclusions: We observed an increase in specific types of child maltreatment during the COVID-19 pandemic. These findings highlight the need for increased attention to children at risk for child abuse and neglect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chiabu.2021.104990DOI Listing
June 2021

Novel Dietary and Lifestyle Inflammation Scores Directly Associated with All-Cause, All-Cancer, and All-Cardiovascular Disease Mortality Risks Among Women.

J Nutr 2021 Apr;151(4):930-939

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Background: Exogenous exposures collectively may contribute to chronic, low-grade inflammation and increase risks for major chronic diseases and mortality. We previously developed, validated, and reported a novel, FFQ-based and lifestyle questionnaire-based, inflammation biomarker panel-weighted, predominantly whole foods-based 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS; comprising physical activity, alcohol intake, BMI, and current smoking status). Both scores were more strongly associated with circulating biomarkers of inflammation in 3 populations than were previously reported dietary inflammation indices. Associations of the DIS and LIS with mortality risk have not been reported.

Objectives: To investigate separate and joint associations of the DIS and LIS with all-cause, all-cancer, and cardiovascular disease (CVD) mortality risks in the prospective Iowa Women's Health Study (1986-2012; n = 33,155 women, ages 55-69 years, of whom 17,431 died during follow-up, including 4379 from cancer and 6574 from CVD).

Methods: We summed each study participant's scores' components, weighted by their published weights, to yield the participant's inflammation score; a higher score was considered more pro-inflammatory. We assessed DIS and LIS mortality associations using multivariable Cox proportional hazards regression.

Results: Among participants in the highest relative to the lowest DIS and LIS quintiles, the adjusted HRs for all-cause mortality were 1.11 (95% CI: 1.05-1.16) and 1.60 (95% CI: 1.53-1.68), respectively; for all-cancer mortality were 1.07 (95% CI: 0.97-1.17) and 1.51 (95% CI: 1.38-1.66), respectively; and for CVD mortality were 1.12 (95% CI: 1.03-1.21) and 1.79 (95% CI: 1.66-1.94), respectively (all Ptrend values < 0.01). Among those in the highest relative to the lowest joint LIS/DIS quintiles, the HRs for all-cause, all-cancer, and all-CVD mortality were 1.88 (95% CI: 1.71-2.08), 1.82 (95% CI: 1.50-2.20), and 1.92 (95% CI: 1.64-2.24), respectively.

Conclusions: More pro-inflammatory diets and lifestyles, separately but especially jointly, may be associated with higher all-cause, all-cancer, and all-CVD mortality risks among women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxaa388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030700PMC
April 2021

Physical Therapy and Health Information Management Students: Perceptions of an Online Interprofessional Education Experience.

Perspect Health Inf Manag 2021 7;18(Winter):1f. Epub 2020 Dec 7.

is an assistant professor at Texas State University College of Health Professions in the Department of Health Information Management.

This study described the results of online interprofessional education (IPE) between physical therapy and health information management students. Using the published (SPICE-R2) survey, this study measured changes in perception about IPE before and after three online interactions. Survey results included an overall score and three factors: Interprofessional Teamwork and Team-Based Practice (T), Roles/Responsibilities for Collaborative Practice (R), and Patient Outcomes from Collaborative Practice (O). Data were analyzed using two-way analysis of variance tests using time and program as factors. The overall scores improved significantly for time (ρ=.019). The T factor demonstrated a significant change for program (ρ=.006) and the R factor improved significantly over time (ρ=.005) and by program (ρ=.022). Narrative student comments focused on role and responsibility clarification, communication and coordination, and participation in a realistic experience involving multiple professions. The students believed that the experience was beneficial and important.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883362PMC
December 2020

Are routine chest X-rays following chest tube removal necessary in asymptomatic pediatric patients?

Pediatr Surg Int 2021 May 1;37(5):631-637. Epub 2021 Jan 1.

Department of Clinical Education and Professional Development, CHOC Children's Hospital of Orange County, 1201 W. La Veta Avenue, Orange, CA, 92868, USA.

Purpose: The purpose of this study was to determine if routine chest X-rays (CXRs) performed after chest tube (CT) removal in pediatric patients provide additional benefit for clinical management compared to observation of symptoms alone.

Methods: A single-center retrospective study was conducted of inpatients, 18 years or younger, who had a CT managed by the pediatric surgery team between July 2017 and May 2019. The study compared two groups: (1) patients who received a post-pull CXR and (2) those who did not. The primary outcome of the study was the need for intervention after CT removal.

Results: 102 patients had 116 CTs and met inclusion criteria; 79 post-pull CXRs were performed; the remaining 37 CT pulls did not have a follow-up CXR. No patients required CT replacement or surgery in the absence of symptoms. Three patients exhibited clinical symptoms that would have prompted intervention regardless of post-pull CXR results. One patient had an intervention guided by post-pull CXR results alone. Meanwhile, another patient had delayed onset of symptoms and intervention. No patients required an intervention in the group that did not have a post-pull CXR.

Conclusion: Chest X-ray after CT removal had a very low yield for changing clinical management of asymptomatic patients. Clinical symptoms predict the need for an intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00383-020-04809-7DOI Listing
May 2021

CRI iAtlas: an interactive portal for immuno-oncology research.

F1000Res 2020 24;9:1028. Epub 2020 Aug 24.

Sage Bionetworks, Seattle, WA, 98101, USA.

The Cancer Research Institute (CRI) iAtlas is an interactive web platform for data exploration and discovery in the context of tumors and their interactions with the immune microenvironment. iAtlas allows researchers to study immune response characterizations and patterns for individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports computation and visualization of correlations and statistics among features related to the tumor microenvironment, cell composition, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, expression of key immunomodulators, and tumor infiltrating lymphocyte (TIL) spatial maps. iAtlas was launched to accompany the release of the TCGA PanCancer Atlas and has since been expanded to include new capabilities such as (1) user-defined loading of sample cohorts, (2) a tool for classifying expression data into immune subtypes, and (3) integration of TIL mapping from digital pathology images. We expect that the CRI iAtlas will accelerate discovery and improve patient outcomes by providing researchers access to standardized immunogenomics data to better understand the tumor immune microenvironment and its impact on patient responses to immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.25141.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658727PMC
April 2021

Prolonged hospital length of stay in pediatric trauma: a model for targeted interventions.

Pediatr Res 2020 Nov 12. Epub 2020 Nov 12.

CHOC Children's Hospital, Orange, CA, USA.

Background: In this study, trauma-specific risk factors of prolonged length of stay (LOS) in pediatric trauma were examined. Statistical and machine learning models were used to proffer ways to improve the quality of care of patients at risk of prolonged length of stay and reduce cost.

Methods: Data from 27 hospitals were retrieved on 81,929 hospitalizations of pediatric patients with a primary diagnosis of trauma, and for which the LOS was >24 h. Nested mixed effects model was used for simplified statistical inference, while a stochastic gradient boosting model, considering high-order statistical interactions, was built for prediction.

Results: Over 18.7% of the encounters had LOS >1 week. Burns and corrosion and suspected and confirmed child abuse are the strongest drivers of prolonged LOS. Several other trauma-specific and general pediatric clinical variables were also predictors of prolonged LOS. The stochastic gradient model obtained an area under the receiver operator characteristic curve of 0.912 (0.907, 0.917).

Conclusions: The high performance of the machine learning model coupled with statistical inference from the mixed effects model provide an opportunity for targeted interventions to improve quality of care of trauma patients likely to require long length of stay.

Impact: Targeted interventions on high-risk patients would improve the quality of care of pediatric trauma patients and reduce the length of stay. This comprehensive study includes data from multiple hospitals analyzed with advanced statistical and machine learning models. The statistical and machine learning models provide opportunities for targeted interventions and reduction in prolonged length of stay reducing the burden of hospitalization on families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-020-01237-0DOI Listing
November 2020

Dietary and Lifestyle Oxidative Balance Scores and Incident Colorectal Cancer Risk among Older Women; the Iowa Women's Health Study.

Nutr Cancer 2020 Sep 28:1-13. Epub 2020 Sep 28.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Background: Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology, but in epidemiologic studies, associations of most individual exposures with CRC have been weak or inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial.

Methods: Using food frequency and lifestyle questionnaire data from the prospective Iowa Women's Health Study (1986-2012), we investigated associations of 11-component dietary and 4-component lifestyle oxidative balance scores (OBS) with incident CRC using multivariable Cox proportional hazards regression.

Results: Of the 33,736 cancer-free women aged 55-69 years at baseline, 1,632 developed CRC during follow-up. Among participants in the highest relative to the lowest dietary and lifestyle OBS quintiles (higher anti-oxidant relative to pro-oxidant exposures), the adjusted hazard ratios (HRs) and their 95% confidence intervals (CI) were, respectively, 0.77 (0.63, 0.94) (=0.02) and 0.61 (0.52, 0.71) (<0.0001). Among those in the highest relative to the lowest joint lifestyle/dietary OBS quintile, the HR was 0.45 (95% CI 0.26, 0.77).

Conclusions: Our findings suggest that a predominance of antioxidant over pro-oxidant dietary and lifestyle exposures-separately and especially jointly-may be inversely associated with CRC risk among older women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01635581.2020.1821904DOI Listing
September 2020

Mapping carbon accumulation potential from global natural forest regrowth.

Nature 2020 09 23;585(7826):545-550. Epub 2020 Sep 23.

Jet Propulsion Laboratory, National Aeronautics and Space Administration, Pasadena, CA, USA.

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide. Regrowing natural forests is a prominent strategy for capturing additional carbon, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC) may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2686-xDOI Listing
September 2020

Inflammation Modulation by Vitamin D and Calcium in the Morphologically Normal Colorectal Mucosa of Patients with Colorectal Adenoma in a Clinical Trial.

Cancer Prev Res (Phila) 2021 Jan 11;14(1):65-76. Epub 2020 Sep 11.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group ( = 0.001), 46% in the calcium group ( = 0.002), and 34% in the calcium + vitamin D group ( = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoform DBP2 ( rs4588*A), the COX-2/15-HPDG ratio decreased 70% ( = 0.0006), 75% ( = 0.0002), and 60% ( = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorably modulate the balance of expression of COX-2 and 15-HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform). PREVENTION RELEVANCE: Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-20-0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947029PMC
January 2021

A multicenter mixed-effects model for inference and prediction of 72-h return visits to the emergency department for adult patients with trauma-related diagnoses.

J Orthop Surg Res 2020 Aug 14;15(1):331. Epub 2020 Aug 14.

Schmid College of Science & Technology, Chapman University, Orange, CA, USA.

Objective: Emergency department (ED) return visits within 72 h may be a sign of poor quality of care and entail unnecessary use of healthcare resources. In this study, we compare the performance of two leading statistical and machine learning classification algorithms, and we use the best performing approach to identify novel risk factors of ED return visits.

Methods: We analyzed 3.2 million ED encounters with at least one diagnosis under "injury, poisoning and certain other consequences of external causes" and "external causes of morbidity." These encounters included patients 18 years or older from across 128 emergency room facilities in the USA. For each encounter, we calculated the 72-h ED return status and retrieved 57 features from demographics, diagnoses, procedures, and medications administered during the process of administration of medical care. We implemented a mixed-effects model to assess the effects of the covariates while accounting for the hierarchical structure of the data. Additionally, we investigated the predictive accuracy of the extreme gradient boosting tree ensemble approach and compared the performance of the two methods.

Results: The mixed-effects model indicates that certain blunt force and non-blunt trauma inflates the risk of a return visit. Notably, patients with trauma to the head and patients with burns and corrosions have elevated risks. This is in addition to 11 other classes of both blunt force and non-blunt force traumas. In addition, prior healthcare resource utilization, patients who have had one or more prior return visits within the last 6 months, prior ED visits, and the number of hospitalizations within the 6 months are associated with increased risk of returning to the ED after discharge. On the one hand, the area under the receiver characteristic curve (AUROC) of the mixed-effects model was 0.710 (0.707, 0.712). On the other hand, the gradient boosting tree ensemble had a lower AUROC of 0.698 CI (0.696, 0.700) on the independent test model.

Conclusions: The proposed mixed-effects model achieved the highest known AUC and resulted in the identification of novel risk factors. The model outperformed one of the leading machine learning ensemble classifiers, the extreme gradient boosting tree in terms of model performance. The risk factors we identified can assist emergency departments to decrease the number of unplanned return visits within 72 h.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-020-01863-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427714PMC
August 2020

A generalizable data-driven multicellular model of pancreatic ductal adenocarcinoma.

Gigascience 2020 07;9(7)

Institute for Systems Biology, 401 Terry Avenue North, Seattle, WA 98109, USA.

Background: Mechanistic models, when combined with pertinent data, can improve our knowledge regarding important molecular and cellular mechanisms found in cancer. These models make the prediction of tissue-level response to drug treatment possible, which can lead to new therapies and improved patient outcomes. Here we present a data-driven multiscale modeling framework to study molecular interactions between cancer, stromal, and immune cells found in the tumor microenvironment. We also develop methods to use molecular data available in The Cancer Genome Atlas to generate sample-specific models of cancer.

Results: By combining published models of different cells relevant to pancreatic ductal adenocarcinoma (PDAC), we built an agent-based model of the multicellular pancreatic tumor microenvironment, formally describing cell type-specific molecular interactions and cytokine-mediated cell-cell communications. We used an ensemble-based modeling approach to systematically explore how variations in the tumor microenvironment affect the viability of cancer cells. The results suggest that the autocrine loop involving EGF signaling is a key interaction modulator between pancreatic cancer and stellate cells. EGF is also found to be associated with previously described subtypes of PDAC. Moreover, the model allows a systematic exploration of the effect of possible therapeutic perturbations; our simulations suggest that reducing bFGF secretion by stellate cells will have, on average, a positive impact on cancer apoptosis.

Conclusions: The developed framework allows model-driven hypotheses to be generated regarding therapeutically relevant PDAC states with potential molecular and cellular drivers indicating specific intervention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gigascience/giaa075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374045PMC
July 2020

Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms.

Int J Cancer 2020 11 25;147(10):2725-2734. Epub 2020 May 25.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)-considered the best marker of total vitamin D exposure-is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 - <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable-adjusted hazard ratios (HRs) for CRC-specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44-3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68-1.22) among cases without Gc2 (P = .0002). The corresponding HRs for all-cause mortality were 1.80 (95% CI 1.24-2.60) among those with Gc2, and 1.12 (95% CI 0.84-1.51) among those without Gc2 (P = .004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529852PMC
November 2020

Intrinsic Genetic and Transcriptomic Patterns Reflect Tumor Immune Subtypes Facilitating Exploring Possible Combinatory Therapy.

Front Mol Biosci 2020 23;7:53. Epub 2020 Apr 23.

Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, China.

The classification of immune subtypes was based on immune signatures highlighting the tumor immuno-microenvironment. It was found that immune subtypes associated with mutation and expression patterns in the tumor. How the intrinsic genetic and transcriptomic alterations contribute to the immune subtypes and how to select drug combinations from both targeted drugs and immune therapeutic drugs according to different immune subtypes are still not clear. Through statistical analysis of genetic alterations and transcriptional profiles of breast invasive carcinoma (BRCA) samples, we found significant differences in the number of somatic missense mutations and frameshift deletions among the different immune subtypes. The high mutation load for somatic missense mutations and frameshift deletions may be explained by the high frequency of mutations and high expression of DNA double-strand break repair pathway genes. Extensive analysis of signaling pathways in both the genetic and transcriptomic levels reveals significantly altered pathways such as tumor protein Tumor Protein P53 (TP53) and receptor tyrosine kinase (RTK)/RAS signaling pathways among different subtypes. Drug targets in the signaling pathways such as mitogen-activated protein kinase kinase kinase 1 (MAP3K1) and Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) show genetic alteration in specific subtypes, which may be potential targets for patients of a specific subtype. More drug targets which show transcriptional difference among immune subtypes were discovered, such as cyclin-dependent kinase (CDK)4, CDK6, Erb-B2 receptor tyrosine kinase 2 (ERBB2), etc. Moreover, differences in functional activity between tumor growth and immune-related pathways also elucidate the extrinsic factors of differences in prognosis and suggest potential drug combinations for different immune subtypes. These results help to explain how intrinsic alterations are associated with the immune subtypes and provide clues for possible combination therapy for different immune subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2020.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191006PMC
April 2020

Prediction of 7-Day Readmission Risk for Pediatric Trauma Patients.

J Surg Res 2020 09 7;253:254-261. Epub 2020 May 7.

Information Systems, Children's Hospital of Orange County, Orange, California.

Background: Pediatric patients admitted for trauma may have unique risk factors of unplanned readmission and require condition-specific models to maximize accuracy of prediction. We used a multicenter data set on trauma admissions to study risk factors and predict unplanned 7-day readmissions with comparison to the 30-day metric.

Methods: Data from 28 hospitals in the United States consisting of 82,532 patients (95,158 encounters) were retrieved, and 75% of the data were used for building a random intercept, mixed-effects regression model, whereas the remaining were used for evaluating model performance. The variables included were demographics, payer, current and past health care utilization, trauma-related and other diagnoses, medications, and surgical procedures.

Results: Certain conditions such as poisoning and medical/surgical complications during treatment of traumatic injuries are associated with increased odds of unplanned readmission. Conversely, trauma-related conditions, such as trauma to the thorax, knee, lower leg, hip/thigh, elbow/forearm, and shoulder/upper arm, are associated with reduced odds of readmission. Additional predictors include the current and past health care utilization and the number of medications. The corresponding 7-day model achieved an area under the receiver operator characteristic curve of 0.737 (0.716, 0.757) on an independent test set and shared similar risk factors with the 30-day version.

Conclusions: Patients with trauma-related conditions have risk of readmission modified by the type of trauma. As a result, additional quality of care measures may be required for patients with trauma-related conditions that elevate their risk of readmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2020.03.068DOI Listing
September 2020

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study.

JNCI Cancer Spectr 2020 Feb 15;4(1):pkz083. Epub 2019 Oct 15.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.

Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, = 1.2 × 10). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) ( = .01).

Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pkz083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050153PMC
February 2020

A Framework for Performance Comparison among Major Electronic Health Record Systems.

Perspect Health Inf Manag 2019 1;16(Fall):1h. Epub 2019 Oct 1.

Texas State University in San Marcos, TX.

While nearly all hospitals have adopted electronic health record (EHR) systems, some are dissatisfied and considering replacement systems to better address unique organizational needs and priorities. With more than 4,000 certified health information technology products available, comparing the vast number of EHR options is complex. This study tested the hypothesis that various EHR systems demonstrate different financial and quality performance and presented a framework for comparison. Using a subscribed database containing US hospitals' observations from 2011 to 2016, we estimated an ordinary least squares regression model with robust standard errors and clustered by year. We regressed the selected finance and quality measures as dependent variables with the vendors' indicators as independent variables, with control variables. This study demonstrated an approach for analyzing performance data to help hospitals distinguish EHR systems on the basis of several organizational outcomes: return on assets, bed utilization rate, Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) summary star rating, and value-based purchasing Total Performance Score. This framework will help EHR acquisition teams make informed decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931047PMC
July 2020

Exploratory Full-Field Strain Analysis of Regenerated Bone Tissue from Osteoinductive Biomaterials.

Materials (Basel) 2020 Jan 1;13(1). Epub 2020 Jan 1.

School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK.

Biomaterials for bone regeneration are constantly under development, and their application in critical-sized defects represents a promising alternative to bone grafting techniques. However, the ability of all these materials to produce bone mechanically comparable with the native tissue remains unclear. This study aims to explore the full-field strain evolution in newly formed bone tissue produced in vivo by different osteoinductive strategies, including delivery systems for BMP-2 release. In situ high-resolution X-ray micro-computed tomography (microCT) and digital volume correlation (DVC) were used to qualitatively assess the micromechanics of regenerated bone tissue. Local strain in the tissue was evaluated in relation to the different bone morphometry and mineralization for specimens ( = 2 p/treatment) retrieved at a single time point (10 weeks in vivo). Results indicated a variety of load-transfer ability for the different treatments, highlighting the mechanical adaptation of bone structure in the early stages of bone healing. Although exploratory due to the limited sample size, the findings and analysis reported herein suggest how the combination of microCT and DVC can provide enhanced understanding of the micromechanics of newly formed bone produced in vivo, with the potential to inform further development of novel bone regeneration approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma13010168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981952PMC
January 2020

ADAPTS: Automated deconvolution augmentation of profiles for tissue specific cells.

PLoS One 2019 19;14(11):e0224693. Epub 2019 Nov 19.

Celgene Corporation, Seattle, Washington, United States of America.

Immune cell infiltration of tumors and the tumor microenvironment can be an important component for determining patient outcomes. For example, immune and stromal cell presence inferred by deconvolving patient gene expression data may help identify high risk patients or suggest a course of treatment. One particularly powerful family of deconvolution techniques uses signature matrices of genes that uniquely identify each cell type as determined from single cell type purified gene expression data. Many methods from this family have been recently published, often including new signature matrices appropriate for a single purpose, such as investigating a specific type of tumor. The package ADAPTS helps users make the most of this expanding knowledge base by introducing a framework for cell type deconvolution. ADAPTS implements modular tools for customizing signature matrices for new tissue types by adding custom cell types or building new matrices de novo, including from single cell RNAseq data. It includes a common interface to several popular deconvolution algorithms that use a signature matrix to estimate the proportion of cell types present in heterogenous samples. ADAPTS also implements a novel method for clustering cell types into groups that are difficult to distinguish by deconvolution and then re-splitting those clusters using hierarchical deconvolution. We demonstrate that the techniques implemented in ADAPTS improve the ability to reconstruct the cell types present in a single cell RNAseq data set in a blind predictive analysis. ADAPTS is currently available for use in R on CRAN and GitHub.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863530PMC
April 2020

Resilience assessment of Puerto Rico's coral reefs to inform reef management.

PLoS One 2019 5;14(11):e0224360. Epub 2019 Nov 5.

U.S. Environmental Protection Agency, Office of Research and Development, Washington, D.C., United States of America.

Globally increasing sea surface temperatures threaten coral reefs, both directly and through interactions with local stressors. More resilient reefs have a higher likelihood of returning to a coral-dominated state following a disturbance, such as a mass bleaching event. To advance practical approaches to reef resilience assessments and aid resilience-based management of coral reefs, we conducted a resilience assessment for Puerto Rico's coral reefs, modified from methods used in other U.S. jurisdictions. We calculated relative resilience scores for 103 sites from an existing commonwealth-wide survey using eight resilience indicators-such as coral diversity, macroalgae percent cover, and herbivorous fish biomass-and assessed which indicators most drove resilience. We found that sites of very different relative resilience were generally highly spatially intermixed, underscoring the importance and necessity of decision making and management at fine scales. In combination with information on levels of two localized stressors (fishing pressure and pollution exposure), we used the resilience indicators to assess which of seven potential management actions could be used at each site to maintain or improve resilience. Fishery management was the management action that applied to the most sites. Furthermore, we combined sites' resilience scores with projected ocean warming to assign sites to vulnerability categories. Island-wide or community-level managers can use the actions and vulnerability information as a starting point for resilience-based management of their reefs. This assessment differs from many previous ones because we tested how much information could be yielded by a "desktop" assessment using freely-available, existing data rather than from a customized, resilience-focused field survey. The available data still permitted analyses comparable to previous assessments, demonstrating that desktop resilience assessments can substitute for assessments with field components under some circumstances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224360PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830742PMC
April 2020

A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning.

Cancers (Basel) 2019 Oct 15;11(10). Epub 2019 Oct 15.

Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we set up and validated a machine learning approach to predict the potential for positive response to ICI. Support vector machines (SVM) and extreme gradient boosting (XGboost) models were developed with a 10×5-fold cross-validation schema on 80% of TCGA cases to predict ICI responsiveness defined by a score combining tumor mutational burden and TGF- β signaling. On the remaining 20% validation subset, our SVM model scored 0.88 accuracy and 0.27 Matthews Correlation Coefficient. The proposed machine learning approach could be useful to predict the putative response to ICI treatment by expression data of primary tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11101562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827166PMC
October 2019

Zebrafish embryo as a replacement model for initial biocompatibility studies of biomaterials and drug delivery systems.

Acta Biomater 2019 12 1;100:235-243. Epub 2019 Oct 1.

Deptartment of Engineering Sciences, Division of Applied Materials Science, Uppsala University, Uppsala, Sweden; Department of Surgical Sciences, Orthopaedics, Uppsala University, Sweden. Electronic address:

The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and in vivo research. In this review, we consider how zebrafish embryos have been utilised to test both the biocompatibility of materials developed to interact with the human body and drug release studies. Furthermore, we outline the advantages and limitations of this model and review legal and ethical issues. We anticipate increasing application of the zebrafish model for biomaterial evaluation in the near future. STATEMENT OF SIGNIFICANCE: This review aims to evaluate the potential application and suitability of the zebrafish model in the development of biomaterials and drug delivery systems. It creates scientific impact and interest because replacement models are desirable to the society and the scientific community. The continuous development of biomaterials calls for the need to provide solutions for biological testing. This review covers the topic of how the FET model can be applied to evaluate biocompatibility. Further, it explores the zebrafish from the wild-type to the mutant form, followed by a discussion about the ethical considerations and concerns when using the FET model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2019.09.038DOI Listing
December 2019

Inherited Melanoma Risk Variants Associated with Histopathologically Amelanotic Melanoma.

J Invest Dermatol 2020 04 27;140(4):918-922.e7. Epub 2019 Sep 27.

Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093215PMC
April 2020

Skin cancer surveillance practices and attitudes among hairdressers: a cross-sectional study in Atlanta, Georgia.

J Am Acad Dermatol 2019 Jul 17. Epub 2019 Jul 17.

Emory University School of Medicine, Emory University, Atlanta, Georgia; Division of Dermatology, Atlanta VA Medical Center, Atlanta, Georgia; Department of Dermatology, Emory University, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2019.07.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374908PMC
July 2019

Genomic and molecular characterization of preterm birth.

Proc Natl Acad Sci U S A 2019 03 4;116(12):5819-5827. Epub 2019 Mar 4.

Institute for Systems Biology, Seattle, WA 98109;

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1716314116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431191PMC
March 2019

Flexibility of Boolean Network Reservoir Computers in Approximating Arbitrary Recursive and Non-Recursive Binary Filters.

Entropy (Basel) 2018 Dec 11;20(12). Epub 2018 Dec 11.

Institute for Systems Biology, 401 Terry Ave N, Seattle, WA 98109, USA.

Reservoir computers (RCs) are biology-inspired computational frameworks for signal processing that are typically implemented using recurrent neural networks. Recent work has shown that Boolean networks (BN) can also be used as reservoirs. We analyze the performance of BN RCs, measuring their flexibility and identifying the factors that determine the effective approximation of Boolean functions applied in a sliding-window fashion over a binary signal, both non-recursively and recursively. We train and test BN RCs of different sizes, signal connectivity, and in-degree to approximate three-bit, five-bit, and three-bit recursive binary functions, respectively. We analyze how BN RC parameters and function average sensitivity, which is a measure of function smoothness, affect approximation accuracy as well as the spread of accuracies for a single reservoir. We found that approximation accuracy and reservoir flexibility are highly dependent on RC parameters. Overall, our results indicate that not all reservoirs are equally flexible, and RC instantiation and training can be more efficient if this is taken into account. The optimum range of RC parameters opens up an angle of exploration for understanding how biological systems might be tuned to balance system restraints with processing capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e20120954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512538PMC
December 2018
-->