Whole-genome doubling confers unique genetic vulnerabilities on tumour cells.

Whole-genome doubling (WGD) is common in human cancers, occurring early in tumorigenesis and generating genetically unstable tetraploid cells that fuel tumour development1,2. Cells that undergo WGD (WGD+ cells) must adapt to accommodate their abnormal tetraploid state; however, the nature of these adaptations, and whether they confer vulnerabilities that can be exploited therapeutically, is unclear. Here, using sequencing data from roughly 10,000 primary human cancer samples and essentiality data from approximately 600 cancer cell lines, we show that WGD gives rise to common genetic traits that are accompanied by unique vulnerabilities. We reveal that WGD+ cells are more dependent than WGD- cells on signalling from the spindle-assembly checkpoint, DNA-replication factors and proteasome function. We also identify KIF18A, which encodes a mitotic kinesin protein, as being specifically required for the viability of WGD+ cells. Although KIF18A is largely dispensable for accurate chromosome segregation during mitosis in WGD- cells, its loss induces notable mitotic errors in WGD+ cells, ultimately impairing cell viability. Collectively, our results suggest new strategies for specifically targeting WGD+ cancer cells while sparing the normal, non-transformed WGD- cells that comprise human tissue.

Characterization and decontamination of background noise in droplet-based single-cell protein expression data with DecontPro.

Assays such as CITE-seq can measure the abundance of cell surface proteins on individual cells using antibody derived tags (ADTs). However, many ADTs have high levels of background noise that can obfuscate down-stream analyses. In an exploratory analysis of PBMC datasets, we find that some droplets that were originally called 'empty' due to low levels of RNA contained high levels of ADTs and likely corresponded to neutrophils. We identified a novel type of artifact in the empty droplets called a 'spongelet' which has medium levels of ADT expression and is distinct from ambient noise. ADT expression levels in the spongelets correlate to ADT expression levels in the background peak of true cells in several datasets suggesting that they can contribute to background noise along with ambient ADTs. We then developed DecontPro, a novel Bayesian hierarchical model that can decontaminate ADT data by estimating and removing contamination from these sources. DecontPro outperforms other decontamination tools in removing aberrantly expressed ADTs while retaining native ADTs and in improving clustering specificity. Overall, these results suggest that identification of empty drops should be performed separately for RNA and ADT data and that DecontPro can be incorporated into CITE-seq workflows to improve the quality of downstream analyses.

Bulk brain tissue cell-type deconvolution with bias correction for single-nuclei RNA sequencing data using DeTREM.

BACKGROUND: Quantifying cell-type abundance in bulk tissue RNA-sequencing enables researchers to better understand complex systems. Newer deconvolution methodologies, such as MuSiC, use cell-type signatures derived from single-cell RNA-sequencing (scRNA-seq) data to make these calculations. Single-nuclei RNA-sequencing (snRNA-seq) reference data can be used instead of scRNA-seq data for tissues such as human brain where single-cell data are difficult to obtain, but accuracy suffers due to sequencing differences between the technologies. RESULTS: We propose a modification to MuSiC entitled 'DeTREM' which compensates for sequencing differences between the cell-type signature and bulk RNA-seq datasets in order to better predict cell-type fractions. We show DeTREM to be more accurate than MuSiC in simulated and real human brain bulk RNA-sequencing datasets with various cell-type abundance estimates. We also compare DeTREM to SCDC and CIBERSORTx, two recent deconvolution methods that use scRNA-seq cell-type signatures. We find that they perform well in simulated data but produce less accurate results than DeTREM when used to deconvolute human brain data. CONCLUSION: DeTREM improves the deconvolution accuracy of MuSiC and outperforms other deconvolution methods when applied to snRNA-seq data. DeTREM enables accurate cell-type deconvolution in situations where scRNA-seq data are not available. This modification improves characterization cell-type specific effects in brain tissue and identification of cell-type abundance differences under various conditions.

Diagnostic and Invasive Colonoscopy Are Not Risk Factors for Revision Surgery Due to Periprosthetic Joint Infection.

BACKGROUND: Colonoscopy is routinely performed for colorectal cancer screening in patients who have a preexisting unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA), or total hip arthroplasty (THA) prostheses. However, colonoscopy is theorized to provoke transient bacteremia, providing a potential nidus for periprosthetic joint infection. This study aimed to investigate the risk of aseptic and septic revision surgery in patients who underwent diagnostic colonoscopy or invasive colonoscopy within one year following UKA, TKA, or THA. METHODS: A retrospective cohort analysis was performed using a national database. Patients were identified using Current Procedural Terminology. In total, 52,891 patients underwent UKA, 1,049,218 underwent TKA, and 526,296 underwent THA. Data were analyzed with univariate analysis preceding multivariable logistic regressions to investigate outcomes of interest at 2 and 3 years from the index procedure. RESULTS: Diagnostic colonoscopy resulted in no increase in odds of all-cause or septic revision surgery for any prostheses. At both time points, invasive colonoscopy resulted in lower odds of all-cause revision (P < .05) for patients with UKA, decreased odds of septic revision (P < .001) for patients with TKA, and decreased odds of both all-cause and septic revision (P < .05) for patients with THA. CONCLUSION: Our results show that diagnostic colonoscopy was not a significant risk factor for revision following UKA, TKA, or THA. Paradoxically, invasive colonoscopy was protective against revision, even with very minimal use of antibiotic prophylaxis observed. This study addresses the theory that colonoscopy procedures may threaten an existing joint prosthesis via transient bacteremia and shows no increase in revision outcomes following colonoscopy. LEVEL OF EVIDENCE: Level III.

Interval Time of at Least 6 Weeks Between Bilateral Total Knee Arthroplasties is Associated With Decreased Postoperative Complications.

BACKGROUND: Staged, bilateral total knee arthroplasty (TKA) has an increased risk of complications if the second procedure is performed before physiologic recovery from the first. The aims of this study were to 1) determine whether there is a time-dependent relationship between TKA staging and rates of revisions and complications and 2) identify data-driven time intervals that reduce risk of revisions and complications. METHODS: Data were collected from a national insurance database from 2015 to 2018. Staged intervals were initially assessed using fixed 6-week intervals. Stratum-specific likelihood ratio analyses were subsequently conducted to observe data-driven staging thresholds. Bivariate and multivariable regression analyses were conducted to determine the associations between the time intervals and 2-year rates of revision surgery and 90-day major complications. We included 25,527 patients undergoing staged bilateral TKA. RESULTS: In comparison to the shortest fixed time interval (1-6 weeks), as the staging interval increased the odds of 2-year all-cause revision and 90-day major complications significantly decreased (P < .05 for all). Stratum-specific likelihood ratio analysis identified 3 data-driven staging categories 1-5, 6-17, and 18-24 weeks that maximized the difference in both 2-year rates of revision and 90-day major complications. CONCLUSION: Our data showed a time-dependent relationship between the timing of TKA stages and complications. If staging is considered, a delayed interval of at least 6 weeks between procedures may significantly reduce revision and major complications. LEVEL OF EVIDENCE: Level III Therapeutic Study.

Extended length of stay in diabetic octogenarians following revision total hip arthroplasty.

PURPOSE: Past research has shown diabetic patients, including those of geriatric age, to be at an increased risk of postoperative complications following various surgeries, including revision total hip arthroplasty (rTHA). However, whether these risks are disproportionately greater in octogenarian patients has not been well investigated. This study aimed to determine whether diabetic octogenarians are at an increased risk of postoperative complications following rTHA. METHODS: The national surgical quality improvement program database was used to identify all diabetic patients who underwent rTHA from 2007 to 2018. Patients were divided into two groups: an aged 65 to 79 cohort and an aged 80 to 89 cohort. Patient demographics, comorbidities, and postoperative complications were assessed and compared between the two aged cohorts, with the utilization of bivariate and multivariate analyses. RESULTS: Of the 1184 diabetic patients who underwent rTHA, 906 (76.5%) patients were in the aged 65 to 79 cohort and 278 (23.5%) patients were in the aged 80 to 89 cohort. After adjusting for patient demographics and medical comorbidities, compared to patients in the aged 65 to 79 group, diabetic patients who were 80 to 89 years old were found to have an increased risk of extended length of hospital stay (OR 1.67; p = 0.017). CONCLUSION: Diabetic octogenarian patients have an increased risk for a prolonged hospital stay following rTHA relative to their younger diabetic geriatric counterparts. Orthopedic surgeons should be aware of these increased risks to properly educate diabetic octogenarians and assist in surgical management decision making in these patients considering rTHA.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

ExperimentSubset: an R package to manage subsets of Bioconductor Experiment objects.

MOTIVATION: R Experiment objects such as the SummarizedExperiment or SingleCellExperiment are data containers for storing one or more matrix-like assays along with associated row and column data. These objects have been used to facilitate the storage and analysis of high-throughput genomic data generated from technologies such as single-cell RNA sequencing. One common computational task in many genomics analysis workflows is to perform subsetting of the data matrix before applying down-stream analytical methods. For example, one may need to subset the columns of the assay matrix to exclude poor-quality samples or subset the rows of the matrix to select the most variable features. Traditionally, a second object is created that contains the desired subset of assay from the original object. However, this approach is inefficient as it requires the creation of an additional object containing a copy of the original assay and leads to challenges with data provenance. RESULTS: To overcome these challenges, we developed an R package called ExperimentSubset, which is a data container that implements classes for efficient storage and streamlined retrieval of assays that have been subsetted by rows and/or columns. These classes are able to inherently provide data provenance by maintaining the relationship between the subsetted and parent assays. We demonstrate the utility of this package on a single-cell RNA-seq dataset by storing and retrieving subsets at different stages of the analysis while maintaining a lower memory footprint. Overall, the ExperimentSubset is a flexible container for the efficient management of subsets. AVAILABILITY AND IMPLEMENTATION: ExperimentSubset package is available at Bioconductor: https://bioconductor.org/packages/ExperimentSubset/ and Github: https://github.com/campbio/ExperimentSubset. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

NetSig: network-based discovery from cancer genomes.

Methods that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes; but such approaches are challenging to validate at scale, and their predictive value remains unclear. We developed a robust statistic (NetSig) that integrates protein interaction networks with data from 4,742 tumor exomes. NetSig can accurately classify known driver genes in 60% of tested tumor types and predicts 62 new driver candidates. Using a quantitative experimental framework to determine in vivo tumorigenic potential in mice, we found that NetSig candidates induce tumors at rates that are comparable to those of known oncogenes and are ten-fold higher than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified. Our study presents a scalable integrated computational and experimental workflow to expand discovery from cancer genomes.

The scope and severity of white-nose syndrome on hibernating bats in North America.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning.

Alcance y Severidad del Síndrome de Nariz Blanca en los Murciélagos Hibernando en América del Norte Resumen La evaluación del alcance y la severidad de las amenazas es necesaria para los análisis de impacto sobre las poblaciones que se usan para orientar a la planeación de la conservación. La evaluación cuantitativa de amenazas con frecuencia requiere de programas de monitoreo que proporcionen datos confiables en escalas espaciales y temporales, aunque dichos programas pueden ser difíciles de justificar hasta que exista un estresante aparente. Gracias a una movilización de esfuerzos de las agencias de manejo de fauna para registrar los conteos invernales de murciélagos hibernadores, recopilamos datos para cinco especies en más de 200 sitios a lo largos de 27 estados de EUA y dos provincias canadienses entre 1995 y 2018 para determinar el impacto del síndrome de nariz blanca (SNB), una enfermedad mortal de los murciélagos hibernadores. Estimamos declinaciones en los conteos invernales de las colonias de murciélagos en sitios en donde el hongo invasivo que ocasiona el SNB (Pseudogymnoascus destructans) había sido detectado para evaluar el impacto de amenaza del SNB. Tres especies que se encuentran bajo valoración por parte del Servicio de Pesca y Vida Silvestre de los EUA (Myotis septentrionalis, Myotis lucifugus y Perimyotis subflavus) tuvieron una declinación de más del 90%, lo que justifica la clasificación de la severidad de la amenaza del SNB como extrema con base en el criterio usado por NatureServe. El alcance de la amenaza del SNB definido por el criterio de NatureServe fue desde amplio (36% de la distribución de Myotis lucifugus) hasta dominante (79% de la distribución de Myotis septentrionalis) para estas especies. Las declinaciones de otras dos especies (Myotis sodalis y Eptesicus fuscus) fueron menos severas, pero de igual manera quedaron clasificadas desde moderada hasta seria con base en los criterios de NatureServe. El intercambio de datos entre las jurisdicciones proporcionó una evaluación completa del alcance y la severidad de la amenaza del SNB e indicó las diferencias regionales que pueden guiar a los esfuerzos de respuesta realizados en las jurisdicciones internacionales, nacionales, estatales o provinciales. Evaluamos el impacto de amenaza de una enfermedad infecciosa emergente mediante la combinación de los esfuerzos de monitoreo que sobrepasan fronteras jurisdiccionales y demostramos la importancia que tienen para la planeación y la evaluación basadas en datos de la conservación los programas de monitoreo coordinados, como el Programa de Monitoreo de los Murciélagos Norteamericanos (NABat).

Does Symptomatic Benign Prostatic Hyperplasia Increase the Risk of Periprosthetic Joint Infection After Primary Total Joint Arthroplasty?

BACKGROUND: Periprosthetic joint infection (PJI) is among the leading causes of failure in total joint arthroplasty. A recently proposed risk factor for PJI is symptomatic benign prostatic hyperplasia (sBPH). This study aims to determine if sBPH is associated with PJI following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Using the Mariner all-payer claims database, 1745 patients with sBPH undergoing primary THA were propensity-matched with 3490 controls, and 3053 patients with sBPH undergoing primary TKA were propensity-matched with 6106 controls. Additionally, the same 1745 patients with sBPH undergoing THA were compared to 317,360 prematched controls, and the same 3053 patients with sBPH undergoing TKA were compared to 557,730 prematched controls. Univariate analysis was conducted using chi-squared or ANOVA where appropriate. RESULTS: At two years postoperatively, patients with sBPH were not at significantly increased risk for PJI following primary THA (1.54% vs 1.43%; P = .745) and TKA (1.99% vs 2.14%; P = .642) relative to postmatch controls. Compared to matched controls, THA patients with sBPH had an increased 90-day incidence of anemia (P < .001), blood transfusion (P < .001), and urinary tract infection (UTI; P < .001). Total knee arthroplasty patients with sBPH had an increased 90-day incidence of anemia (P < .001), blood transfusion (P < .001), cellulitis (P = .023), renal failure (P = .030), heart failure (P = .029), and UTI (P < .001) relative to matched controls. CONCLUSION: In primary THA and TKA, sBPH does not appear to be an independent risk factor for PJI within two years postoperatively. However, clinicians should be cognizant of the significantly increased risk for postoperative UTI in this patient population.

Preoperative Anemia Independently Predicts Significantly Increased Odds of Short-Term Complications Following Aseptic Revision Hip and Knee Arthroplasty.

BACKGROUND: Preoperative anemia is an important risk factor for developing complications following revision hip (rTHA) and knee (rTKA) arthroplasty. We aim to determine the effect of anemia severity on 30-day postoperative complications following revision hip and knee arthroplasty. METHODS: A retrospective cohort study was conducted using the American College of Surgeons National Quality Improvement Program Database. All patients who underwent revision joint arthroplasty (rTJA) between 2006 to 2017 were identified and grouped based upon the hematocrit (Hct) level. Anemia was defined as Hct <36% for women and <39% for men, and further stratified into mild anemia (Hct 33% to 36% for women, Hct 33% to 39% for men), and moderate to severe anemia (Hct <33% for both men and women). Univariate and multivariate analysis were used to evaluate the incidence of multiple adverse events within 30 days after TJA. RESULTS: A total of 8932 patients undergoing rTHA and 13,313 patients undergoing rTKA were included for analysis. On multivariate adjustment, patients undergoing rTHA with moderate to severe anemia had an increased odds of 5.437 (95% Confidence Interval (CI) 4.604 to 6.421; P < .001) of developing any postoperative complication. On multivariate adjustment, patients undergoing rTKA with moderate to severe anemia had increased odds of 6.731 (95% Confidence Interval (CI) 5.540 to 8.179; P < .001) of developing any postoperative complication. CONCLUSION: The increasing severity of anemia was associated with an increasing risk of developing any postoperative complication and death following revision hip and knee arthroplasty. There is a significant trend between diminishing preoperative hematocrit levels and increasing odds of postoperative complication.

Preoperative estimated glomerular filtration rate is a marker for postoperative complications following aseptic revision total hip arthroplasty.

INTRODUCTION: Revision total hip arthroplasty (rTHA) is increasingly performed but may carry a high rate of complication. This aim of the study was to determine if a decreased eGFR increases risks of postoperative complications following rTHA. METHODS: A retrospective cohort study using the American College of Surgeons National Quality Improvement Program Database was conducted. Patients undergoing rTHA between 2007 and 2014 were identified and stratified by glomerular filtration rates (eGFR): eGFR > 125 mL/min, eGFR 90-125 mL/min, eGFR 60-90 mL/min, eGFR 30-60 mL/min, and eGFR < 30 mL/min. The incidence of postoperative adverse events within 30 days, including cardiac, pulmonary, renal, septic, thromboembolic, urinary tract, and wound complications, blood transfusion, death, length of stay > 7 days, and unplanned return to the operating room, was assessed. The complication rates following rTHA were assessed with univariate and multivariate analysis with a significance set at p < 0.05. RESULTS: In total, 8898 revision THA procedures were included for analysis. 28.4% of patients that underwent rTHA developed a complication following surgery. Following adjustment, an eGFR of less than 30 mL/min independently increased the odds of any complication (OR 1.447; 95% C.I. 1.010-2.074; p = 0.044), cardiac complications (OR 3.344; 95% C.I. 1.040-10.752; p = 0.043), blood transfusion (O.R. 1.623; 95% C.I. 1.122-2.352; p = 0.010), and extended length of stay (O.R. 2.392; 95% C.I. 1.526-3.759; p < 0.001) when compared to normal renal function. CONCLUSIONS: Diminished eGFR of less than 30 mL/min increased the odds of total complications, cardiac complications, blood transfusions, and extended length of stay compared to normal renal function.

scruff: an R/Bioconductor package for preprocessing single-cell RNA-sequencing data.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) enables the high-throughput quantification of transcriptional profiles in single cells. In contrast to bulk RNA-seq, additional preprocessing steps such as cell barcode identification or unique molecular identifier (UMI) deconvolution are necessary for preprocessing of data from single cell protocols. R packages that can easily preprocess data and rapidly visualize quality metrics and read alignments for individual cells across multiple samples or runs are still lacking. RESULTS: Here we present scruff, an R/Bioconductor package that preprocesses data generated from the CEL-Seq or CEL-Seq2 protocols and reports comprehensive data quality metrics and visualizations. scruff rapidly demultiplexes, aligns, and counts the reads mapped to genome features with deduplication of unique molecular identifier (UMI) tags. scruff also provides novel and extensive functions to visualize both pre- and post-alignment data quality metrics for cells from multiple experiments. Detailed read alignments with corresponding UMI information can be visualized at specific genome coordinates to display differences in isoform usage. The package also supports the visualization of quality metrics for sequence alignment files for multiple experiments generated by Cell Ranger from 10X Genomics. scruff is available as a free and open-source R/Bioconductor package. CONCLUSIONS: scruff streamlines the preprocessing of scRNA-seq data in a few simple R commands. It performs data demultiplexing, alignment, counting, quality report and visualization systematically and comprehensively, ensuring reproducible and reliable analysis of scRNA-seq data.

Invertebrate community response to coarse woody debris removal for bioenergy production from intensively managed forests.

Increased market viability of harvest residues as forest bioenergy feedstock may escalate removal of coarse woody debris in managed forests. Meanwhile, many forest invertebrates use coarse woody debris for cover, food, and reproduction. Few studies have explicitly addressed effects of operational-scale woody biomass harvesting on invertebrates following clearcutting. Therefore, we measured invertebrate community response to large-scale harvest residue removal and micro-site manipulations of harvest residue availability in recently clearcut, intensively managed loblolly pine (Pinus taeda) forests in North Carolina (NC; n = 4) and Georgia (GA; n = 4), USA. We captured 39,794 surface-active invertebrates representing 171 taxonomic groups using pitfall traps situated among micro-site locations (i.e., purposefully retained piles of hardwood stems and piles of conifer stems and areas without coarse woody debris in NC; windrows and no windrows in GA). Micro-site locations were located within six, large-scale treatments (7.16-14.3 ha) in clearcuts. Large-scale treatments represented intensive harvest residue removal, 15% and 30% harvest residue retention, and no harvest residue removal. In NC, ground beetles (Coleoptera: Carabidae) and crickets (Orthoptera: Gryllidae) were three times more abundant in treatments with no harvest residue removal than those with the most intensive harvest residue removal and were reduced in treatments that retained 15% or 30% of harvest residues, although not significantly. Invertebrate taxa richness was greater at micro-site locations with retained hardwood and pine (Pinus spp.) harvest residues than those with minimal amounts of coarse woody debris. In both states, relative abundances of several invertebrate taxa, including cave crickets (Orthoptera: Rhaphidophoridae), fungus gnats (Diptera: Mycetophilidae and Sciaridae), millipedes (Diplopoda), and wood roaches (Blattodea: Ectobiidae), were greater at micro-site locations with retained harvest residues than those with minimal coarse woody debris. Intensified woody biomass harvesting without retention of ≥15% of harvest residue volume may reduce invertebrate taxa richness and abundances of some key invertebrate taxa in regenerating stands. Further, harvest residue management during and after woody biomass harvesting may be an important consideration for maintaining invertebrate diversity and conserving invertebrates that are influential in the maintenance of ecosystem function and integrity in young forests.

Proceedings of the American Association of Oral and Maxillofacial Surgeon's 2017 Clinical and Scientific Innovations in Oral and Maxillofacial Surgery (CSIOMS).

The sixth biennial Clinical and Scientific Innovations in Oral and Maxillofacial Surgery, formerly the Research Summit, of the American Association of Oral and Maxillofacial Surgeons and its Committee on Research Planning and Technology Assessment was held in Rosemont, Illinois from April 28 to 30, 2017. The goal of the symposium is to provide a forum for the latest clinical and scientific advances to be brought to the specialty. It also nurtures collaboration and the development of relationships between oral and maxillofacial surgeons and researchers to bridge the gap between clinical and basic science. The goal is to improve the care of oral and maxillofacial surgical patients through the advancement of translational and clinical research.

Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a 'causal' role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology.

Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research.

Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent microscopy, and biochemical techniques such as genetic identification and antibody capture have provided easier and more sensitive platforms for detecting and diagnosing diseases as well as providing new fundamental insight into disease progression. These advancements have led to the development of new technology and assays capable of easy and early detection of pathogenicity as well as the enhancement of the drug discovery and development pipeline. While some studies have focused on treatment, many of these technologies have found initial success in laboratories as a precursor for clinical applications. This review highlights the current and future progress of microfluidic techniques geared toward the timely and inexpensive diagnosis of disease including technologies aimed at high-throughput single cell analysis for drug development. It also summarizes novel microfluidic approaches to characterize fundamental cellular behavior and heterogeneity.

Genomic approaches to accelerate cancer interception.

Although major advances have been reported in the last decade in the treatment of late-stage cancer with targeted and immune-based therapies, there is a crucial unmet need to develop new approaches to improve the prevention and early detection of cancer. Advances in genomics and computational biology offer unprecedented opportunities to understand the earliest molecular events associated with carcinogenesis, enabling novel strategies to intercept the development of invasive cancers. This Series paper will highlight emerging big data genomic approaches with the potential to accelerate advances in cancer prevention, screening, and early detection across various tumour types, and the challenges inherent in the development of these tools for clinical use. Through coordinated multicentre consortia, these genomic approaches are likely to transform the landscape of cancer interception in the coming years.