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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 289 records · Page 16
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation

The early stages of Alzheimer’s disease (AD) involve interactions between multiple pathophysiological processes. Although these processes are well studied, we still lack robust tools to predict individualised trajectories of disease progression. Here, we employ a robust and interpretable machine learning approach to combine multimodal biological data and predict future pathological tau accumulation. In particular, we use machine learning to quantify interactions between key pathological markers (β-amyloid, medial temporal lobe atrophy, tau and APOE 4) at mildly impaired and asymptomatic stages of AD. Using baseline non-tau markers we derive a prognostic index that: (a) stratifies patients based on future pathological tau accumulation, (b) predicts individualised regional future rate of tau accumulation, and (c) translates predictions from deep phenotyping patient cohorts to cognitively normal individuals. Our results propose a robust approach for fine scale stratification and prognostication with translation impact for clinical trial design targeting the earliest stages of AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

Abstract Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94; 700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82–1.05 for 7000 mg [ p (overall) = 0.88] and 0.81–1.21 for 700 mg [ p (overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [ p = 0.97], 7000 mg; 24 vs 20.5 days [ p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2. Trial Registration: ClinicalTrials.gov Identifier: NCT04518410.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Altered ß-cell Prohormone Processing and Secretion in Type 1 Diabetes

Analysis of data from clinical cohorts and more recently from human pancreatic tissue, indicate that defects in prohormone processing are an early and persistent component of type 1 diabetes pathogenesis. In this Perspectives article, we review the current state of knowledge of alterations in islet prohormone expression and processing in type 1 diabetes, and consider the clinical impact of these findings. Lingering questions, including pathologic etiologies and consequences of altered prohormone expression and secretion in type 1 diabetes, and the natural history of circulating prohormone production in health and disease are considered. Finally, key steps required to move forward in this area are outlined, including longitudinal testing of relevant clinical populations, studies that probe the genetics of altered prohormone processing, the need for combined functional and histologic testing of human pancreatic tissues, continued interrogation of the intersection between prohormone processing and autoimmunity, and optimal assays or approaches for analysis. Successful resolution of these questions may offer the potential to use altered prohormone processing as a pathogenic anchor that can be used to cluster different endotypes enveloping a large set of variables, and inform therapeutic strategies aimed at personalized intervention in the natural history of type 1 diabetes.

Islets, Insulin, Proinsulin, Islet Amyloid Polypep↗
DOE OSTI2022

From Mouse to Human: Cellular Morphometric Subtype Learned From Mouse Mammary Tumors Provides Prognostic Value in Human Breast Cancer

Mouse models of cancer provide a powerful tool for investigating all aspects of cancer biology. In this study, we used our recently developed machine learning approach to identify the cellular morphometric biomarkers (CMB) from digital images of hematoxylin and eosin (H&E) micrographs of orthotopic Trp53-null mammary tumors (n = 154) and to discover the corresponding cellular morphometric subtypes (CMS). Of the two CMS identified, CMS-2 was significantly associated with shorter survival (p = 0.0084). We then evaluated the learned CMB and corresponding CMS model in MMTV-Erbb2 transgenic mouse mammary tumors (n = 53) in which CMS-2 was significantly correlated with the presence of metastasis (p = 0.004). We next evaluated the mouse CMB and CMS model on The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort (n = 1017). Kaplan–Meier analysis showed significantly shorter overall survival (OS) of CMS-2 patients compared to CMS-1 patients (p = 0.024) and added significant prognostic value in multi-variable analysis of clinical and molecular factors, namely, age, pathological stage, and PAM50 molecular subtype. Thus, application of CMS to digital images of routine workflow H&E preparations can provide unbiased biological stratification to inform patient care.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Combining Machine Learning and Comparative Effectiveness Methodology to Study Primary Care Pharmacotherapy Pathways for Veterans With Depression

Our objective is to demonstrate an innovative method combining machine learning with comparative effectiveness research techniques and to investigate a hitherto unstudied question about the effectiveness of common prescribing patterns. For Operation Enduring Freedom/Operation Iraqi Freedom veterans with major depressive disorder, we generate pharmacotherapy pathways (of antidepressants) using process mining and machine learning. We select the medication episodes that were started at subtherapeutic doses by the first assigned primary care physician and observe the paths that those medication episodes follow. Using 2-stage least squares, we test the effectiveness of starting at a low dose and staying low for longer versus ramping up fast while balancing observable and unobservable characteristics of patients and providers through instrumental variables. We leverage predetermined provider practice patterns as instruments. We collected outpatient pharmacy data for selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, patient and provider characteristics (as control variables), and the instruments for our cohort. All data were extracted for the period between 2006 and 2020. There is a statistically significant positive effect (0.68, 95% CI 0.11–1.25) of “ramping up fast” on engagement in care. When we examine the effect of “ramping up slow”, we see an insignificant negative impact on engagement in care (−0.82, 95% CI −1.89 to 0.25). As expected, the probability of drop-out also seems to have a negative effect on engagement in care (−0.39, 95% CI −0.94 to 0.17). We further validate these results by testing with medication possession ratios calculated periodically as an alternative engagement in care metric. Our findings contradict the “Start low, go slow” adage, indicating that ramping up the dose of an antidepressant faster has a significantly positive effect on engagement in care for our population.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Targeted metagenomic assessment reflects critical colonization in battlefield injuries

Current diagnostics and clinical management strategies for combat wounds are based on decisions made by expert clinicians. However, even in the hands of experienced surgeons, wounds from combat injuries can exhibit failed healing and complications related to limitations in the rapid and comprehensive generation of diagnostic information. Previous studies have demonstrated the possible use of genomic sequencing approaches to detect microbial signatures involved in combat casualty care. While effective, whole metagenome sequencing is limited by the depth required to confidently detect all relevant signatures. To address this, we developed a targeted capture sequencing panel to detect microbial signatures relevant to wound healing. These targets include known microbial nosocomial pathogens, wound colonizers, and genes involved in virulence and antimicrobial resistance. A bioinformatics pipeline was built to identify genomic regions of interest and over 8,000 oligonucleotide probes were designed for capture. The panel was synthesized and validated using control reference genomes in human background and on wound-effluent samples from a cohort of combat-injured U.S. service members. Our panel was sensitive against wound-colonizing species, Acinetobacter baumannii and Pseudomonas aeruginosa, and was specific in detecting corresponding virulence and antimicrobial-resistance genes as well as other pathogenic species present in microflora mixtures. Random forest feature permutation confirmed the prevalence of Acinetobacter and Pseudomonas in critically colonized wounds and wounds that failed to heal, respectively. Our results demonstrate the capability of targeted sequencing tools and analysis platforms to profile and deliver information on pathogenic factors influencing wound progression, thereby guiding therapeutic intervention.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Proteomic and phosphoproteomic measurements enhance ability to predict ex vivo drug response in AML

Acute Myeloid Leukemia (AML) affects 20,000 patients in the US annually with a five-year survival rate of approximately 25%. One reason for the low survival rate is the high prevalence of clonal evolution that gives rise to heterogeneous sub-populations of leukemic cells with diverse mutation spectra, which eventually leads to disease relapse. This genetic heterogeneity drives the activation of complex signaling pathways that is reflected at the protein level. This diversity makes it difficult to treat AML with targeted therapy, requiring custom patient treatment protocols tailored to each individual’s leukemia. Toward this end, the Beat AML research program prospectively collected genomic and transcriptomic data from over 1000 AML patients and carried out ex vivo drug sensitivity assays to identify genomic signatures that could predict patient-specific drug responses. However, there are inherent weaknesses in using only genetic and transcriptomic measurements as surrogates of drug response, particularly the absence of direct information about phosphorylation-mediated signal transduction. As a member of the Clinical Proteomic Tumor Analysis Consortium, we have extended the molecular characterization of this cohort by collecting proteomic and phosphoproteomic measurements from a subset of these patient samples (38 in total) to evaluate the hypothesis that proteomic signatures can improve the ability to predict response to 26 drugs in AML ex vivo samples. In this work we describe our systematic, multi-omic approach to evaluate proteomic signatures of drug response and compare protein levels to other markers of drug response such as mutational patterns. We explore the nuances of this approach using two drugs that target key pathways activated in AML: quizartinib (FLT3) and trametinib (Ras/MEK), and show how patient-derived signatures can be interpreted biologically and validated in cell lines. In conclusion, this pilot study demonstrates strong promise for proteomics-based patient stratification to assess drug sensitivity in AML.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Overcoming Resilience Challenges on the Outer Banks of North Carolina

In 2021, the Town of Nags Head, located in the Outer Banks region of North Carolina, was among the first cohort of coastal and island communities to participate in the U.S. Department of Energy's Energy Transitions Initiative Partnership Project (ETIPP), which offers technical assistance and cash awards to competitively selected coastal, remote, and island communities seeking to transform their energy systems and increase their energy resilience. As a barrier island separated from mainland North Carolina, Nags Head experiences impacts from extreme weather events, including power outages, especially during hurricane season. To address challenges, the Nags Head ETIPP team sought to improve the town's disaster resilience by ensuring that critical facilities can remain powered during and after extreme events. With support from experts at Sandia National Laboratories, the National Renewable Energy Laboratory, and the Coastal Studies Institute, the community team identified the following goals for its participation in ETIPP: 1. Identify and prioritize critical facilities that, when powered during disruptions, support the town's resilience. 2. Analyze the potential for on-site solar photovoltaic (PV) and storage systems at 2-4 prioritized critical facilities owned and/or operated by the town. 3. Analyze the potential for interconnecting solar PV and storage systems at a cluster of public and privately owned facilities into a resilient microgrid. 4. Explore finance options and utility interconnection requirements and compensation mechanisms. 5. Summarize outcomes and next steps for town leadership.

25 ENERGY STORAGE↗
DOE OSTI2025

Assessment of diagenesis in archaeological human second metacarpal bones using the intensity of the small angle X-ray scattering D -period peak

Bone consists mainly of carbonated apatite (cAp) nanoplatelets embedded in a matrix of collagen fibrils. Earlier, high-energy small angle X-ray scattering (SAXS) studies of archaeological adult human second metacarpal bones (mc2) found collagen D-period peaks with high-intensity I D in specimens in which microcomputed tomography (microCT) showed little diagenesis and I D ~ 0 for specimens where microCT revealed severe diagenesis (Park et al. 2022 Int. J. Osteoarchaeol. 32, 170–181 (doi:10.1002/oa.3053); Stock et al. 2022 Int. J. Osteoarchaeol. 32, 120–131 (doi:10.1002/oa.3049)). Here, the present paper uses SAXS at beamline 1-ID, Advanced Photon Source, Argonne National Laboratory and other techniques to study a set of 10 mc2 from an early Medieval cemetery at Greding, Germany. We hypothesized that non-invasive measurement of I D would provide an accurate and rapid (approx. 6 min/specimen) assessment of diagenesis in archaeological mc2. Results of Raman spectroscopy, laboratory microCT and backscattered electron, reflected light and polarized transmitted light microscopies confirmed the SAXS determinations, but lattice parameter values from X-ray diffraction were uncorrelated with I D value. Age-at-death estimates placed the 10 mc2 in three age categories (young adult, middle adult, old adult): lattice parameters from X-ray diffraction were uncorrelated with age at death. Cross-sectional bone area fraction from microCT dropped noticeably for the older age cohort.

Raman spectroscopy↗
DOE OSTI2023

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy

In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Radium Dial Workers: Back to the Future

This report reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. The mortality experience of 3,276 radium dial painters and handlers employed between 1913-1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2022

Prognostic importance of the preoperative New‐Naples prognostic score for patients with gastric cancer

Abstract Background The wide applicability of the Naples prognostic score (NPS) is still worthy of further study in gastric cancer (GC). This study aimed to construct a New‐NPS based on the differences in immunity and nutrition in patients with upper and lower gastrointestinal tumors to help obtain an individualized prediction of prognosis. Methods This study retrospectively analyzed patients who underwent radical gastrectomy from April 2014 to September 2016. The cutoff values of the preoperative neutrophil‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), serum albumin (Alb), and total cholesterol (TC) were calculated by ROC curve analysis. ROC and t‐ROC were used to evaluate the accuracy of the prognostic markers. The Kaplan–Meier method and log‐rank test were used to analyze the overall survival probability. Univariate and multivariate analyses based on Cox risk regression were used to show the independent predictors. The nomogram was made by R studio. The predictive accuracy of nomogram was assessed using a calibration plot, concordance index (C‐index), and decision curve. Results A total of 737 patients were included in training cohort, 411 patients were included in validation cohort. ROC showed that the New‐NPS was more suitable for predicting the prognosis of GC patients. NPS = 2 indicated a poor prognosis. Multivariate analysis showed that CEA ( P = 0.026), Borrmann type ( P = 0.001), pTNM ( P < 0.001), New‐NPS ( P < 0.001), and nerve infiltration ( P = 0.035) were independent risk factors for prognosis. Conclusion The New‐NPS based on the cutoff values of NLR, LMR, Alb, and TC is not only suitable for predicting prognosis but can also be combined with clinicopathological characteristics to construct a nomogram model for GC patients.

Wang, Hao↗
DOE OSTI2022

Acute Copper Toxicity Displays a Nonmonotonic Relationship with Age Across the Medaka ( Oryzias latipes ) Life Span

The ability of an organism to cope with environmental stressors varies across the life span because of developmental stage–specific responses and age-related functional declines. In the present study, we examined the effect of age on acute copper toxicity in Japanese medaka (Oryzias latipes). We first determined the median lethal concentration (LC50) at 96 h for embryos, 7-day-old fry, and 6-month-old medaka. Embryos were exposed to 0, 15, 30, 60, 125, 250, and 500 ppb CuSO 4 through hatching. Fry were exposed to 0, 20, 50, 75, 100, 150, 250, and 500 ppb CuSO 4 for 96 h. Adult fish were exposed to 0, 100, 150, 200, 250, and 300 ppb CuSO 4 for 96 h. The 96-h LC50 was 804 ppb for embryos, 262 ppb for embryonically exposed larvae, 60.3 ppb for 7-day-old fry, and 226 ppb for adults. We then challenged cohorts of fish aged 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, and 16 months with a 225-ppb CuSO 4 exposure to determine the acute toxicity across the life span. The fish exhibited a bimodal tolerance to copper, with tolerance peaking in 2- and 3-month-old fish and again at 10 and 11 months of age. Our data demonstrate that copper sensitivity is dynamic throughout the medaka life span and may be influenced by trade-offs with reproduction. Environ Toxicol Chem 2022;41:2999–3006. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Virulence factors and antimicrobial resistance profiles of Campylobacter isolates recovered from consecutively reused broiler litter

ABSTRACT Campylobacterinfections are a leading cause of bacterial diarrhea in humans globally. Infections are due to consumption of contaminated food products and are highly associated with chicken meat, with chickens being an important reservoir forCampylobacter. Here, we characterized the genetic diversity ofCampylobacter jejuni(C. jejuni) andCampylobacter coli(C. coli) detected in broiler chicken litter over three consecutive flocks and determined their antimicrobial resistance (ARM) and virulence factor (VF) profiles.Campylobacterwas detected in 9.38% (27/288) of litter samples collected. Antimicrobial susceptibility testing and whole genome sequencing were performed onC. jejuni(n= 39) andC. coli(n= 5) isolates.Campylobactervirulence factors differed within and across broiler houses but were explained by the broiler flock cohort raised on litter,Campylobacterspecies andCampylobactermultilocus sequence type (MLST). Virulence factors involved in the ability to invade and colonize host tissues and evade host defenses were present inC. jejuniisolates (ST-464) from flock cohorts 1 and 2 but absent inC. jejuniisolates (ST-48) from flock cohort 3.C. jejuniisolates from house three harbored a significantly higher proportion of virulence genes with functions related to glycosylation and immune evasion thanC. jejuniisolates from houses 1 and 2 (P< 0.01). AllC. jejuniisolates were susceptible to all antibiotics tested whileC. coli(n= 4) were resistant to tetracycline and harbored the tetracycline resistant ribosomal protection protein (TetO). Our results suggest that house environment and broiler management practices imposed selective pressures on virulence factors and antimicrobial resistance genes ofCampylobacter. IMPORTANCE Campylobacteris a leading cause of foodborne illness in the United States due to consumption of contaminated or mishandled food products, often associated with chicken meat.Campylobacteris common in the microbiota of avian and mammalian gut; however, acquisition of antimicrobial resistance genes (ARGs) and virulence factors (VFs) may result in strains that pose significant threat to public health. Although there are studies investigating the genetic diversity ofCampylobacterstrains isolated from post-harvest chicken samples, there are limited data on the genome characteristics of isolates recovered from preharvest broiler production. Here, we show thatCampylobacter jejuniandCampylobacter colidiffer in their carriage of antimicrobial resistance and virulence factors may also differ in their ability to persist in litter during consecutive grow-out of broiler flocks. We found that presence/absence of virulence factors needed for evasion of host defense mechanisms and gut colonization played an integral role in differentiatingCampylobacterstrains.

Microbiology↗
DOE OSTI2020

A nomogram for prediction of stage III/IV gastric cancer outcome after surgery: A multicenter population‐based study

Abstract Most patients with gastric cancer (GC) are first diagnosed at stage III‐IV and surgery resection remains the primary therapeutic modality for these patients. However, clinical staging used for prediction of those patients provides limited information. We collected clinicopathological data and disease‐progression information from 508 patients with stage III‐IV GC at three Chinese hospitals and 1298 patients from the Surveillance, Epidemiology, and End Results database. Based on the stepwise multivariate regression model, we constructed a novel nomogram to predict overall survival (OS). The performance of discrimination for this model was measured using Harrell's concordance index (C‐index) and receiver‐operating characteristic curve (ROC), and was validated using calibration plots. Multivariate Cox regression analyses showed that tumor size, age at diagnosis, N stage, tumor grade, and distant metastases were outstanding independent prognostic factors of stage III‐IV GC. We developed a nomogram based on these five prognostic predictors. In the training set, the C‐index of the nomogram was 0.645 (95% CI: 0.611‐0.679), which was higher than that of the American Joint Committee on Cancer TNM system alone (sixth TNM: 0.544; seventh TNM: 0.575; eighth TNM: 0.568). Similar results were observed in validation cohort. Moreover, calibration blots demonstrated good consistency between the actual and predicted OS probabilities. According to the nomogram, GC individuals could be classified into three groups (low‐, middle‐, and high‐risk) ( P < .001). Our nomogram complements the current staging system for prediction of individual prognosis with stage III‐IV GC, and may be helpful for making individualized treatment decisions.

Gao, Zhiying↗