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Background: Direct-to-consumer promotion of lung cancer screening has increased, especially low-dose computed tomography (CT). However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported.Objective: To quantify the cumulative risk that a person who participated in a 1- or 2-year lung cancer screening examination would receive at least 1 false-positive result, as well as rates of unnecessary diagnostic procedures.Design: Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.gov registration number: NCT00006382)Setting: Feasibility study for the ongoing National Lung Screening Trial.Patients: Current or former smokers, aged 55 to 74 years, with a smoking history of 30 pack-years or more and no history of lung cancer (n = 3190).Intervention: Random assignment to low-dose CT or chest radiography with baseline and 1 repeated annual screening; 1-year follow-up after the final screening. Randomization was centralized and stratified by age, sex, and study center.Measurements: False-positive screenings, defined as a positive screening with a completed negative work-up or 12 months or more of follow-up with no lung cancer diagnosis.Results: By using a Kaplan-Meier analysis, a person's cumulative probability of 1 or more false-positive low-dose CT examinations was 21% (95% CI, 19% to 23%) after 1 screening and 33% (CI, 31% to 35%) after 2. The rates for chest radiography were 9% (CI, 8% to 11%) and 15% (CI, 13% to 16%), respectively. A total of 7% of participants with a false-positive low-dose CT examination and 4% with a false-positive chest radiography had a resulting invasive procedure.Limitations: Screening was limited to 2 rounds. Follow-up after the second screening was limited to 12 months. The false-negative rate is probably an underestimate.Conclusion: Risks for false-positive results on lung cancer screening tests are substantial after only 2 annual examinations, particularly for low-dose CT. Further study of resulting economic, psychosocial, and physical burdens of these methods is warranted.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Calcium and vitamin D have been hypothesized to reduce colorectal cancer risk. Epidemiological evidence, however, is mixed.Methods: To explore those relationships, data were collected as part of a population-based, case-control study of colorectal cancer in Wisconsin women (678 controls, 348 colon and 164 rectal cancer cases). A semi-quantitative food frequency questionnaire was used to ascertain food and dietary supplement intake 2 years prior to interview. Logistic regression models were used to calculate odds ratios (OR).Results: Higher levels of calcium intake were associated with reduced colon and rectal cancer risk. The following adjusted OR and 95% confidence intervals (CI) were observed, comparing the fifth quintile (based on control intake) with the first: colon cancer: OR = 0.6, 95% CI: 0.4-1.0, P-trend: 0.03; rectal cancer: OR = 0.6, 95% CI: 0.3-1.1, P-trend: 0.07. Similar relationships were observed for vitamin D intake, although OR were closer to the null value and did not always behave in a step-wise fashion (fifth quintile versus the first--colon cancer: OR = 0.7, 95% CI: 0.4-1.1, P-trend: 0.05; rectal cancer: OR = 0.8, 95% CI: 0.5-1.5, P-trend: 0.42).Conclusion: These data support a protective association of calcium on colon and rectal cancer risk. [ABSTRACT FROM AUTHOR]

Background and Study Aim: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.Methods: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was <50 cm or visual inspection was limited to <90% of the mucosal surface but without detection of a polyp or mass).Results: Of 7084 (11%) participants with inadequate FSG at baseline, 6496 (91.7%) had <50 cm depth of insertion (75.3% due to patient discomfort) and 500 (7.1%) participants had adequate depth of insertion but suboptimal bowel preparation. Compared to 55-59 year age group, advancing age in 5-year increments (odds ratios (OR) from 1.08 to 1.51) and female sex (OR = 2.40; 95% confidence interval (CI): 2.27-2.54) were associated with inadequate FSG. Obesity (BMI > 30 kg/m(2)) was associated with reduced odds (OR = 0.67; 95% CI: 0.62-0.72). Inadequate FSG screening at baseline was associated with inadequate FSG at repeat screening (OR = 6.24; 95% CI: 5.78-6.75).Conclusions: Sedation should be considered for patients with inadequate FSG or an alternative colorectal cancer screening method should be recommended. [ABSTRACT FROM AUTHOR]

With the increasing production and use of polyurethanes (PUs), it is necessary to develop sustainable techniques for the remediation of plastic pollution. The use of microorganisms capable of biodegrading PUs may be an environmentally desirable solution for controlling these plastic contaminants. To contribute to the discovery of alternatives for the mitigation of plastics in the environment, this study aimed to explore the potential of StaphylococcuswarneriUFV&#95;01.21, isolated from the gut of Galleria mellonellalarvae, for biodegradation of PU in pure culture and microbial co-culture with Serratia liquefaciensL135. S. warneri grew using Impranil® PU as the sole carbon source in pure culture and co-culture. With six days of incubation, the biodegradation of Impranil® in Luria Bertani broth was 96, 88 and 76%, while in minimal medium, it was 58, 54 and 42% for S. warneri, S. liquefaciens, and co-culture, respectively. In addition, S. warneri in pure culture or co-culture was able to biodegrade, adhere and form biofilms on the surfaces of Impranil® disks and poly[4,4'-methylenebis (phenyl isocyanate)-alt-1,4-butanediol/di(propylene glycol)/polycaprolactone] (PCLMDI) films. Scanning electron microscopy also revealed biodegradation by detecting the formation of cracks, furrows, pores, and roughness on the surfaces of inoculated PU, both with pure culture and microbial co-culture. This study is the first to demonstrate the potential of S. warneriin PU biodegradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Bovine seminal plasma proteins perform several functions related to sperm function. Changes in the expression pattern or abundance of seminal proteins are related to changes in the fertilizing capacity of bulls. Considering the role of seminal plasma proteins in sperm function and animal reproduction, we investigated changes in the protein abundance profile in response to sperm morphological changes using a proteomic approach., Datadescription: In our present investigation, we employed liquid chromatography coupled with mass spectrometry to elucidate the proteomic composition of seminal plasma obtained from Nellore bulls exhibiting varying percentages of sperm abnormalities. Following semen collection, seminal plasma was promptly isolated from sperm, and proteins were subsequently precipitated, enzymatically digested using porcine trypsin, and subjected to analysis utilizing the Acquity nano UHPLC System in conjunction with a mass spectrometer. This dataset encompasses a total of 297 proteins, marking the inaugural instance in which a comparative profile of seminal plasma proteins in young Nellore bulls, categorized by their sperm abnormality percentages, has been delineated using LC-MS/MS. The comprehensive nature of this dataset contributes pivotal proteomic insights, representing a noteworthy advancement in our understanding of the reproductive biology of the Nellore breed., (© 2024. The Author(s).)

Background: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies., Methods: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336., Results: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors., Conclusion: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting., (© 2024. The Author(s).)

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 μg ml -1 against Pseudomonas aeruginosa ATCC 27853, 16.25 μg ml -1 against S . enterica Typhimurium ATCC 13311, and 32.50 μg ml -1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 μg ml -1 ) and P. aeruginosa P2307 (65.00 μg ml -1 ) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S . enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S . enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant S almonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.

Urban floods will continue to be an alarming issue worldwide due to climate change and urban expansion. The costly and less environmentally friendly grey infrastructure is not always the most adequate solution to resolve urban pluvial flooding issues. The combination of grey and blue-green infrastructures, also called hybrid infrastructure, has been considered a promising solution for urban stormwater management. Existing approaches for identifying suitable hybrid solutions frequently rely on global multi-objective optimization algorithms. We developed a pre-screening method that decomposes a drainage network into clusters of pipes connected to sub-catchments, based on pipe hydraulic characteristic that allows for the impact of infrastructure combinations (blue-green and grey) to be mapped. Four impact matrices are proposed to map the total, local, upstream, and downstream flood reduction of all possible blue-green, grey, and hybrid solutions. Using an urban catchment in Guangzhou (China) as a case study, results showed that such an exercise could identify prime candidate locations for blue-green and grey infrastructure while filtering out ineffective locations for flood reduction. Furthermore, the impact matrices enabled the identification of flood zones where blue-green infrastructure could handle flood mitigation without the need of local grey infrastructure upgrades. As such, they are not only useful for quick screening of suitable interventions for each flooded zone, but can also potentially serve as a priori knowledge before diving into the data and computationally expensive process of finding the most effective flood mitigation solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Sexual rest is a transient condition, which compromises conception rates, characterized by large volumes of ejaculate with high percentages of dead sperm observed in bulls. The biochemical mechanisms leading to this ejaculate pattern are not fully understood. Six adult resting Nellore bulls were submitted to Breeding Soundness Evaluation by four consecutive semen collections through the electroejaculation method during a 30 min period. Each ejaculate had its semen phenotypic parameters; morphology and physical aspects were evaluated. To assess enzymatic activity (superoxide dismutase, catalase, and glutathione S-transferase), lipid peroxidation (concentrations of malondialdehyde and nitric oxide), fatty acid, and proteomic profile aliquots of spermatozoa from the first and fourth ejaculates were used. All sperm parameters differed between the first and fourth ejaculates. Spermatozoa from the first ejaculate showed lower enzymatic activity and a higher concentration of lipid peroxidation markers. Among the 19 identified fatty acids, 52.7% are polyunsaturated. Relative abundance analysis showed that C12:0 and C18:0 fatty acids differed between the first and fourth ejaculates, being the fourth ejaculate richer in spermatozoa. The proteomics analysis identified a total of 974 proteins in both sample groups (first and fourth ejaculates). The majority of identified proteins are related to cellular processes and signaling. Quantitative proteomics showed 36 differentially abundant proteins, 6 up-regulated proteins in the first ejaculate, and 30 up-regulated proteins in the fourth ejaculate. Spermatozoa from bulls at sexual rest have less antioxidant capacity, causing changes in their fatty acid composition and protein profile, which generates the observed sperm pattern and lower fertilization capacity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Salivary gland (SG) hypofunction (objectively reduced saliva flow rate) and xerostomia (subjective sensation of dry mouth) are common and burdensome side effects of radiotherapy to the head and neck region. Currently, only sparse symptomatic treatment is available to ease the discomfort of xerostomia. The objective of this study is to assess the effect of mesenchymal stem cell (MSC) therapy on SG function after radiation-induced injury., Methods: This systematic review will include animal intervention studies assessing efficacy and safety of MSCs in treating radiation-induced SG hypofunction. The primary outcome is the effect of MSC administration on salivary flow rates (SFR), by comparing treated groups to control groups when available. Secondary outcomes are morphological and immunohistochemical effects as well as safety of MSC treatment. Electronic searches in MEDLINE (PubMed) and Embase databases will be constructed and validated according to the peer review of electronic search strategies (PRESS) and assessed by two independent researchers. Data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Risk of bias will be evaluated with the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool., Discussion: Thus far, critical appraisal of MSC therapy as an effective treatment for SG hypofunction caused solely by radiation injury has not been conducted. A summary of the existing literature on preclinical studies concerning this issue can provide valuable information about effectiveness, mode of action, and safety, allowing further optimization of preclinical and clinical trials., Systematic Review Registration: PROSPERO CRD42021227336., (© 2022. The Author(s).)

Acute lymphoblastic leukaemia (ALL) is an aggressive haematolymphoid malignancy. The prognosis of ALL is excellent in paediatric population, however the outcome of relapse/refractory disease is dismal. Adult ALL has less favourable prognosis and relapse/refractory disease is not uncommonly encountered. Bortezomib is the first generation proteasome inhibitor licensed to treat plasma cell myeloma and mantle cell lymphoma with favourable side effect profile. Efficacy of bortezomib had been proven in other solid tumors. Clinical studies showed promising response for proteasome inhibitors in treating relapse/refractory ALL. Thus, proteasome inhibitors are attractive alternative agents for research in treating ALL. In the review article, we will introduce different proteasome inhibitors and their difference in pharmacological properties. Moreover, the mechanism of action of proteasome inhibitors on ALL will be highlighted. Finally, results of various clinical studies on proteasome inhibitors in both paediatric and adult ALL will be discussed. This review article provides the insights on the use of proteasome inhibitors in treating ALL with a summary of mechanism of action in ALL which facilitates future research on its use to improve the outcome of ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sin and Man.)

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T lymphoblastic leukemia (T-ALL) identified in 2009, due to its unique immunophenotypic and genomic profile. The outcome of patients was poor in earlier studies, and they were prone to have induction failure, with more frequent relapse/refractory disease. Recent advances had been made in discoveries of genetic aberrations and molecular pathogenesis of ETP-ALL. However, the diagnosis and management of ETP-ALL is still challenging. There are limited choices of novel therapies so far. In this review article, it highlighted the diagnostic issue of ETP-ALL, pitfall in diagnosis, and strategy of accurate diagnosis. The review also summarized current understanding of molecular mechanism of leukemogenesis. The emerging role of risk-adapted therapy and allogenic stem cell transplant in optimizing the outcome of patients with ETP-ALL was discussed. Finally, some potential novel therapies were proposed based on the current understanding of molecular pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sin and Man.)

Drought stress is major abiotic stress that affects soybean production. Therefore, it is widely desirable that soybean becomes more tolerant to stress. To provide insights into regulatory mechanisms of the stress response, we compared the global gene expression profiles from leaves of two soybean genotypes that display different responses to water-deficit (BR 16 and Embrapa 48, drought-sensitive and drought-tolerant, respectively). After the RNA-seq analysis, a total of 5335 down-regulated and 3170 up-regulated genes were identified in the BR16. On the other hand, the number of genes differentially expressed was markedly lower in the Embrapa 48, 355 up-regulated and 471 down-regulated genes. However, induction and expression of protein kinases and transcription factors indicated signaling cascades involved in the drought tolerance. Overall, the results suggest that the metabolism of pectin is differently modulated in response to drought stress and may play a role in the soybean defense mechanism against drought. This occurs via an increase of the cell wall plasticity and crosslink, which contributed to a higher hydraulic conductance ( K f ) and relative water content (RWC%). The drought-tolerance mechanism of the Embrapa 48 genotype involves remodeling of the cell wall and increase of the hydraulic conductance to the maintenance of cell turgor and metabolic processes, resulting in the highest leaf RWC, photosynthetic rate ( A ), transpiration ( E ) and carboxylation ( A / C i ). Thus, we concluded that the cell wall adjustment under drought is important for a more efficient water use which promoted a more active photosynthetic metabolism, maintaining higher plant growth under drought stress., Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-021-00043-4., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Agricultural Information Institute, Chinese Academy of Agricultural Sciences 2021.)

Sustainable urban drainage systems (SuDS) help in stormwater management by reducing runoff volume, increasing runoff concentration time and thereby improving the drainage system capacity. This study investigated the potential and cost-effectiveness of SuDS in reducing combined sewer overflows (CSOs). We simulated the performance of four SuDS techniques (bioretention cell, permeable pavement, rain barrel and green roof) at incremental levels of spatial coverage for a small urban catchment with a combined sewer system. We also used an Analytic Hierarchy Process (AHP) considering end-point CSO, land use, imperviousness, slope and elevation criteria to identify priority areas for SuDS deployment. Results showed that CSO volume attenuation ranged a maximum of 50-99% for the catchment, depending on the deployment strategy and underlying mechanisms of each technology. We also found that deployment of SuDS in AHP-selected sub-catchments improved CSO reduction only for rain barrels and green roofs, but not for bioretention cells and permeable pavements. SuDS were also a cost-effective retrofit option: for a 40% volume reduction, the SuDS cost, at most, 25% of the equivalent cost required for a large CSO tank. Outcomes of this study demonstrate the efficacy of SuDS in controlling CSOs, adding yet another tangible benefit to their increasingly recognised multi-functionality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Overdiagnosed cancers are those that are screen-detected but never would have been symptomatic during patients' lifetimes. Indolent cancers are overdiagnosed cancers. Non-indolent cancers can be overdiagnosed when patients die of causes other than the screen-detected cancer and would have, in the absence of screening, been asymptomatic and undiagnosed at the time of death. This is termed competing cause of mortality (CCM) overdiagnosis. Deaths soon after screen detection may represent CCM overdiagnosis. We examined time from screen-detection to death among the 35 participants in the National Lung Screening Trial (NLST) low-dose computed tomography arm with screen-detected lung cancer and died of non-lung-cancer causes. Seven participants died within 6 months, and 20 died more than 24 months after diagnosis. Deaths due to non-lung cancer causes soon after screen detection were uncommon, arguing against widespread CCM overdiagnosis in the NLST. However, CCM overdiagnosis is likely more frequent in community-based screening given the higher prevalence of comorbidities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Surface characteristics play a vital role in simulations for urban bioclimatic conditions. Changing relationships and distribution patterns of sealed and vegetated surfaces as well as building geometry across different scales in urban environments influence surface temperatures. Cities comprise different urban forms, which, depending on their surface characteristics, enhance the heating process, increasing the emergence of urban heat islands (UHIs). Detecting priority areas to introduce multi-beneficial climate change adaptation measures is set to be a key task for the cities long-term strategies to improve climatic conditions across different urban structures and scales. We introduce a simple and fast spatial modelling approach to carry out fine-scale simulations for land surface temperature (LST), mean radiant temperature (MRT) and Universal Thermal Climate Index (UTCI) in a 2D environment. Capabilities of our modelling approach are demonstrated in evaluating urban thermal comfort in the alpine city of Innsbruck, the capital of Tyrol in western Austria. Results show a major contrast between sealed and vegetated surfaces reflected in the distributional patterns and values of LST, MRT and UTCI, correlating with the appearance and frequency of specific surface classes. We found the Sky View Factor to have a substantial impact on calculations for bioclimatic conditions and see high-albedo surfaces decrease LST but increase the apparent temperature (MRT and UTCI values) effecting human thermal comfort. Furthermore, MRT and UTCI are more sensitive to changes in emissivity values, whereas LST is more sensitive to changes in Bowen Ratio values. Application of our modelling approach can be used to identify priority areas and maximise multi-functionality of climate change adaptation measures, to support urban planning processes for heat mitigation and the implementation of policy suggestions to achieve sustainable development goals and other political objectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Oleaginous yeasts have stood out due to their ability to accumulate oil, which can be used for fatty acid-derived biofuel production. Papiliotrema laurentii UFV-1 is capable of starting the lipid accumulation in the late exponential growth phase and achieves maximum lipid content at 48 h of growth; it is, therefore, interesting to study how its oleaginous phenotype is regulated. Herein, we provide for the first time insights into the regulation of this phenotype in P. laurentii UFV-1. We sequenced and assembled its genome, performed comparative genomic analyses and investigated its phylogenetic relationships with other yeasts. Gene expression and metabolomic analyses were carried out on the P. laurentii UFV-1 cultivated under a nitrogen-limiting condition. Our results indicated that the lipogenesis of P. laurentii might have taken place during evolution after the divergence of genera in the phylum Basidiomycota. Metabolomic data indicated the redirection of the carbon flux towards fatty acid synthesis in response to the nitrogen limitation. Furthermore, purine seems to be catabolized to recycle nitrogen and leucine catabolization may provide acetyl-CoA for fatty acid synthesis. Analyses of the expression of genes encoding certain enzymes involved with the oleaginous phenotype indicated that the NADP + -dependent malic enzyme seems to play an important role in the supply of NADPH for fatty acid synthesis. There was a surprising decrease in the expression of the ACC1 gene, which encodes acetyl-CoA carboxylase, during lipid accumulation. Taken together, our results provided a basis for understanding lipid accumulation in P. laurentii under nitrogen limiting conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Numerous organizations, including the United States Preventive Services Task Force, recommend annual lung cancer screening (LCS) with low-dose CT for high risk adults who meet specific criteria. Despite recommendations and national coverage for screening eligible adults through the Centers for Medicare and Medicaid Services, LCS uptake in the United States remains low (<4%). In recognition of the need to improve and understand LCS across the population, as part of the larger Population-based Research to Optimize the Screening PRocess (PROSPR) consortium, the NCI (Bethesda, MD) funded the Lung PROSPR Research Consortium consisting of five diverse healthcare systems in Colorado, Hawaii, Michigan, Pennsylvania, and Wisconsin. Using various methods and data sources, the center aims to examine utilization and outcomes of LCS across diverse populations, and assess how variations in the implementation of LCS programs shape outcomes across the screening process. This commentary presents the PROSPR LCS process model, which outlines the interrelated steps needed to complete the screening process from risk assessment to treatment. In addition to guiding planned projects within the Lung PROSPR Research Consortium, this model provides insights on the complex steps needed to implement, evaluate, and improve LCS outcomes in community practice., (©2019 American Association for Cancer Research.)

When proteostasis is disrupted by stresses such as heat shock, the heat stress response will be stimulated, leading to up-regulation of molecular chaperones by transcriptional activation and mRNA stabilization for restoring proteostasis. Although the mechanisms for their transcriptional activation have been clearly defined, how chaperone mRNAs are stabilized remains largely unknown. Starting by exploring the coupling between the apparently unrelated RNA degradation and protein quality control (PQC) systems, we show that the Dis3 ribonuclease, catalytic subunit of the RNA exosome required for RNA degradation, suppresses PQC activity in unstressed cells by degrading mRNAs encoding the Hsp70 cofactors Sis1, Ydj1 and Fes1, as well as some other chaperones or PQC factors, thereby limiting their protein expression. Dis3 is stabilized through its binding to Sis1 and the Hsp70s Ssa1/2. Upon heat stress, loss of Sis1 and Ssa1/2 availability triggers Dis3 ubiquitination and degradation, leading to stabilization of those chaperone mRNAs originally targeted by Dis3. We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington's disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: Cancer screening tests have helped to reduce cancer deaths. We provide an overview of recent research pertaining to the definition, health impact, and prevalence of several screening tests. We also discuss the multilevel correlates and determinants of screening and interventions designed to increase uptake. Design: Narrative review. Results: Epidemiologic evidence supports the effectiveness of several cancer screening tests in reducing mortality and are therefore routinely recommended. Nevertheless, uptake of routine screening falls short of recommendations in many countries, especially for colorectal cancer. Screening behaviour varies according to sociodemographic factors in addition to a range of other correlates and determinants at multiple levels. Though health behaviour theories have frequently been used to understand and identify intrapersonal level mechanisms to improve screening uptake, research suggests that additional factors from psychological and affective science, decision science, and behavioural economics should also be considered. Empirical support exists for patient education and provider recommendation interventions. Recent research has considered interventions at other levels, such as clinic, with mixed results. Conclusion: As screening recommendations evolve and become more nuanced with personalised screening, psychologists are well-placed to consider psychological factors, in conjunction with factors from other levels, that are helpful in understanding and changing screening behaviour.

The bacterium Actinobacillus pleuropneumoniae is the etiological agent of Contagious Porcine Pleuropneumonia, a disease responsible for economic losses in the swine industry worldwide. A. pleuropneumoniae is capable of producing proteinaceous exotoxins responsible for inducing hemorrhagic lesions, one of which is ApxI. Few studies have conducted an in-depth evaluation of polymorphisms of the nucleotides that make up the ApxI toxin gene. Here we analyze the polymorphisms of the apxIA gene region of A. pleuropneumoniae serovar 5 isolated from swine in different regions in Brazil and report the results of molecular sequencing and phylogenetic analysis. Analysis of the apxIA gene in 60 isolates revealed the presence of genetic diversity and variability. The polymorphisms in the nucleotide sequences determined the grouping of the Brazilian sequences and five more sequences from the GenBank database into 14 different haplotypes, which formed three main groups and revealed the presence of mutations in the nucleotide sequences. The estimation of selection pressures suggests the occurrence of genetic variations by positive selective pressure on A. pleuropneumoniae in large groups of animals in relatively small spaces. These conditions presumably favor the horizontal dissemination of apxIA gene mutations within bacterial populations with host reservoirs. As a result, the same serovar can demonstrate different antigenic capacities due to mutations in the apxIA gene. These alterations in sequences of the apxIA gene could occur in other areas of countries with intense swine production, which could lead to differences in the pathogenicity and immunogenicity of each serovar and have implications for the clinical status or diagnosis of A. pleuropneumoniae., Competing Interests: The authors have declared that no competing interests exist.

The Lung Screening Study was a multicenter controlled feasibility trial that randomly assigned subjects to undergo two rounds of screening with either low-dose spiral computed tomography (LDCT) or chest X-ray (CXR). Long-term follow-up was performed to evaluate any differences in lung-cancer-specific and all-cause mortality between arms. In 2000, subjects were randomly assigned at six screening centers. Linkage with the National Death Index was performed to ascertain long-term mortality for subjects. Median follow-up for mortality of the 1660 and 1658 subjects randomly assigned to LDCT and CXR, respectively, was 5.2 years. There were 32 and 26 deaths from lung cancer in the two groups, respectively, corresponding to lung cancer death rates of 3.84 and 3.10 per 1000 person-years, and a risk ratio of 1.24 (95% confidence interval = 0.74 to 2.08). The risk ratio for all-cause mortality was 1.20 (95% confidence interval = 0.94 to 1.54). These findings can contribute to the overall knowledge on LDCT lung cancer screening.

Purposes: Despite recommendations against prostate cancer screening with prostate-specific antigen (PSA) tests, about one-fourth of men age ≥40 years received PSA tests in 2015. This study aimed to answer 3 questions for men who had a PSA test in the past year: (1) What percentage of these men received the test first suggested by physicians? (2) What factors were associated with physician-initiated PSA testing (PIPT) versus patient/someone else-initiated testing? (3) What percentage of patients ever had shared decision-making when tests were initiated by physicians?, Methods: We analyzed the 2000 and 2015 National Health Interview Survey data. We calculated age-standardized prevalence of PIPT for both years. For 2015, we used logistic regression to calculate adjusted prevalence ratios for PIPT. We also calculated the prevalence of ever discussing both advantages and disadvantages., Results: The age-standardized prevalence of PIPT was significantly higher in 2015 (84.9%) than in 2000 (72.3%). In 2015, nearly 90% of PSA screenings for men aged ≥70 years were suggested by physicians. PIPT was positively associated with 2 or more comorbid conditions and number of patient visits to the doctor. Less than one-third of men reported they had ever participated in a discussion of advantages and disadvantages of PSA testing., Conclusions: The majority of men who had PSA testing in the past year reported that their physicians were the first to suggest testing, including men aged ≥70 years. Our study also points to the challenges and needs in conducting shared decision-making before PSA testing in clinical practice., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Introduction: Recommendations for prostate-specific antigen-based screening for prostate cancer are placing increasing emphasis on men aged 55-69 years. The goal of the current study is to describe patterns of population-based prostate-specific antigen testing with details about that age group., Methods: National Health Interview Surveys from 2005 to 2015 were analyzed in 2017 to estimate routine prostate-specific antigen testing in the past year from self-reported data by age group (40-54, 55-69, ≥70 years), and also by risk group, defined as African American men or men with a family history of prostate cancer versus other men. Differences between successive survey years by age and risk groups were assessed by predicted margins and rate ratios with 99% CIs, using logistic regressions., Results: Prostate-specific antigen testing among men aged 55-69 years decreased from a high of 43.1% (95% CI=40.3, 46.1) in 2008 to a low of 32.8% (95% CI=30.8, 34.7) in 2013, with no significant change in 2015 at 33.8% (95% CI=31.3, 36.4). Men aged ≥70 years had consistently high prevalence in all survey years, ranging from 51.1% in 2008 to 36.4% in 2015. African American men, men with a family history of prostate cancer, and other men showed a 5% absolute decrease over time, but this reduction was significant only in other men., Conclusions: Despite decreases, the absolute change in prostate-specific antigen testing for men aged 55-69 years was small (9.3%) over the study period. Men aged ≥70 years, for whom the benefits are unlikely to exceed the harms, continue to have consistently high testing prevalence., (Published by Elsevier Inc.)

Background: Failure to perform a comprehensive search when designing a systematic review (SR) can lead to bias, reducing the validity of review's conclusions., Objective: We examined the frequency and choice of databases used by reviewers in clinical neurology., Methods: Ninety-five SRs and/or meta-analyses were located across five prominent neurology journals between 2008 and 2014. Methods sections were reviewed, and all bibliographic databases were coded., Results: On average, 2.59 databases were used in SR searches. Seven reviews included an information specialist, and these reviews reported a greater number of information sources used during the search process. Thirty-nine databases were reported across studies. PubMed/MEDLINE ® and EMBASE were cited most frequently., Discussion: Searching too few databases may reduce the validity and generalisability of SR results. We found that the majority of systematic reviewers in clinical neurology do not search an adequate number of databases, which may yield a biased sample of primary studies and, thus, may influence the accuracy of summary effects., Conclusions: Systematic reviewers should aim to search a sufficient number of databases to minimise selection bias. Additionally, systematic reviewers should include information specialists in designing SR methodology, as this may improve systematic review quality., (© 2017 Health Libraries Group.)

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled "Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps". The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial. Cancer Epidemiol Biomarkers Prev; 25(11); 1449-55. ©2016 AACR., Competing Interests: of Potential Conflicts of Interest M.K. Gould reports receiving other commercial support from Archimedes. No potential conflicts of interest were disclosed by the other authors., (©2016 American Association for Cancer Research.)

Background/aims: Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer., Methods: Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death., Results: In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as compared with the published finding of 20% (95% confidence interval: 6.7-26.7)., Conclusion: Death review may not be necessary for primary-outcome analyses in lung cancer screening trials. If deemed necessary, researchers should strive to streamline the death review process as much as possible., (© The Author(s) 2016.)

Triatomines are hematophagous arthropods that transmit Trypanosoma cruzi and Trypanosoma rangeli. Feeding behavior and pathogen transmission is known to vary between the different species, and this characteristic is directly or indirectly dependent on the bioactive molecules of the saliva that facilitate the vector-host-parasite interaction. Here, we identify, characterize and compare the sialoproteomic (from the Greek sialo: saliva) repertoire of important species of the main triatomine genera in the Americas (Rhodnius prolixus, Triatoma lecticularia and Panstrongylus herreri) to better explain this interaction through two-dimensional electrophoresis and mass spectrometry. We identified 221 proteins, 69 from R. prolixus, 100 from T. lecticularia and 52 from P. herreri. We identified high abundance molecules with a great potential to modulate host defenses and homeostasis, highlighting Nitrophorin-4 (28.7%), Salivary lipocalin-5 (65.2%) and Putative triabin (20.5%) in R. prolixus, T. lecticularia and P. herreri, respectively. We also observed that only a single hypothetical protein is shared among three species, which was not functionally categorized. This study corroborates previous findings with R. prolixus, increasing the knowledge about this species with relevant proteomic information and comparisons with the other two targets of the study, T. lecticularia and P. herreri, for which no studies are available from a proteomics perspective., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The data presented here were obtained from the saliva of three triatominae, Rhodnius prolixus, Triatoma lecticularia and Panstrongylus herreri from Montandon et al. study, doi:10.1016/j.ibmb.2016.02.009 [3]. These data were obtained from spectra generated by the mass spectrometry of proteins observed through the analysis of 2-D electrophoretic profiles. The data were analyzed according to the UniProt code, protein name, protein group, isoelectric point and molecular weight, electrophoretic profile, molecular mass referring to UniProt, volume percentage referring to the spot of the electrophoretic profile, number of peptides and percent coverage found by mass spectrometry related to the particular proteins. In addition, there characterizations made the most significant protein per spot, and also characterizations made for biological processes and molecular functions for all identified proteins.

Objective: To obtain information from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial regarding their perception of the retention materials employed by the screening centers. Also, to determine the viability of using email or the internet as a data collection tool with an older population., Design: Three of ten PLCO screening centers queried participants towards the end of the study (2010) as to their opinions of the various retention materials and whether they would have been willing to use electronic communication for study activities, had the option been available., Setting: The questionnaires were administered by mail, and responses were returned to the originating screening center., Participants: The participants in this study consisted of all the active participants at three PLCO screening centers: the University of Colorado Anschutz Medical Campus, the University of Utah, and Henry Ford Health System., Methods: A short, self-administered questionnaire was mailed to all active participants at three PLCO centers (n=41,482). This was a one-time mailing with no follow-up, as the responses were designed to be anonymous in order to obtain the most honest responses., Results: The response rate was 62%. Of respondents, 97% reported their PLCO experience was good or excellent. Nearly 50% of respondents indicated that receipt of an annual newsletter made them more likely to participate; newsletter features they reported as most important were those that conveyed information on cancer, study findings, and how their data were being used. Results did not support study coordinators' suppositions that receipt of a token gift or birthday card by participants was important for retention. Fewer than 30% of respondents indicated that they would have been unwilling to use a secure website to complete study forms., Conclusion: These data indicate the importance of querying participants rather than relying on impressions of study staff, and also indicate that the internet will be a viable means of data collection in future prevention studies that include older Americans., (© 2015 Marshfield Clinic.)

Targeted cancer screening refers to use of disease risk information to identify those most likely to benefit from screening. Researchers have begun to explore the possibility of refining screening regimens for average-risk individuals using genetic and non-genetic risk factors and previous screening experience. Average-risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without comorbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. In this paper, we describe the goals of targeted cancer screening in average-risk individuals, present factors on which cancer screening has been targeted, discuss inclusion of targeting in screening guidelines issued by major U.S. professional organizations, and present evidence to support or question such inclusion. Screening guidelines for average-risk individuals currently target age; smoking (lung cancer only); and, in some instances, race; family history of cancer; and previous negative screening history (cervical cancer only). No guidelines include common genomic polymorphisms. RCTs suggest that targeting certain ages and smoking histories reduces disease-specific cancer mortality, although some guidelines extend ages and smoking histories based on statistical modeling. Guidelines that are based on modestly elevated disease risk typically have either no or little evidence of an ability to affect a mortality benefit. In time, targeted cancer screening is likely to include genetic factors and past screening experience as well as non-genetic factors other than age, smoking, and race, but it is of utmost importance that clinical implementation be evidence-based., (Published by Elsevier Inc.)

Background: It is unclear whether the higher rate of colorectal cancer (CRC) among non-Hispanic blacks (blacks) is due to lower rates of CRC screening or greater biologic risk., Objective: We aimed to evaluate whether blacks are more likely than non-Hispanic whites (whites) to develop distal colon neoplasia (adenoma and/or cancer) after negative flexible sigmoidoscopy (FSG)., Design: We analyzed data of participants with negative FSGs at baseline in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial who underwent repeat FSGs 3 or 5 years later. Subjects with polyps or masses were referred to their physicians for diagnostic colonoscopy. We collected and reviewed the records of diagnostic evaluations., Participants: Our analytic cohort consisted of 21,550 whites and 975 blacks., Main Measures: We did a comparison by race (whites vs. blacks) in the findings of polyps or masses at repeat FSG, the follow-up of abnormal test results and the detection of colorectal neoplasia at diagnostic colonoscopy., Key Results: At the follow-up FSG examination, 304 blacks (31.2 %) and 4183 whites (19.4 %) had abnormal FSG, [adjusted relative risk (RR) = 1.00; 95 % confidence interval (CI), 0.90-1.10]. However, blacks were less likely to undergo diagnostic colonoscopy (76.6 % vs. 83.1 %; RR = 0.90; 95 % CI, 0.84-0.96). Among all included patients, blacks had similar risk of any distal adenoma (RR = 0.86; 95 % CI, 0.65-1.14) and distal advanced adenoma (RR = 1.01; 95 % CI, 0.60-1.68). Similar results were obtained when we restricted our analysis to compliant subjects who underwent diagnostic colonoscopy (RR = 1.01; 95 % CI, 0.80-1.29) for any distal adenoma and (RR = 1.18; 95 % CI, 0.73-1.92) for distal advanced adenoma., Conclusions: We did not find any differences between blacks and whites in the risk of distal colorectal adenoma 3-5 years after negative FSG. However, follow-up evaluations were lower among blacks.

We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist) was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.

The aim of cancer screening is to detect asymptomatic cancers whose treatment will result in extension of life, relative to length of life absent screening. Unfortunately, cancer screening also results in overdiagnosis, the detection of cancers that, in the absence of screening, would not present symptomatically during one's lifetime. Thus, their detection and subsequent treatment is unnecessary and detrimental. This definition of overdiagnosis, while succinct, does not capture the ways it can occur, and our interactions with patients, advocates, researchers, clinicians, and journalists have led us to believe that the concept of overdiagnosis is difficult to explain and, for some, difficult to accept. We propose a dichotomy, the "tumor-patient" classification, to aid in understanding overdiagnosis. The tumor category includes asymptomatic malignant disease that would regress spontaneously if left alone, as well as asymptomatic malignant disease that stagnates or progresses too slowly to be life threatening in even the longest of lifetimes. The patient category includes asymptomatic malignant disease that would progress quickly enough to be life threatening during a lifetime of typical length, but lacks clinical relevance because death due to another cause intercedes prior to what would have been the date of symptomatic diagnosis had screening not occurred. Cancer screening of most organs is likely to result in overdiagnosis of both types. However, the ratio of tumor- to patient-driven overdiagnosis almost certainly varies, and may vary drastically, by organ, screening modality, patient characteristics, and other factors., (© Published by Oxford University Press 2015.)

This study showcases the dynamic simulation capabilities of the Urban Biophysical Environments And Technologies Simulator (UrbanBEATS) on a Melbourne catchment. UrbanBEATS simulates the planning, design and implementation of water sensitive urban design (WSUD) infrastructure in urban environments. It considers explicitly the interaction between urban and water infrastructure planning through time. The model generates a large number of realizations of different WSUD interventions and their evolution through time based on a user-defined scenario. UrbanBEATS' dynamics was tested for the first time on a historical case study of Scotchman's Creek catchment and was trained using historical data (e.g. planning documents, narratives, urban development and societal information) to adequately reproduce patterns of uptake of specific WSUD technologies. The trained model was also used to explore the implications of more stringent future water management objectives. Results highlighted the challenges of meeting this legislation and the opportunities that can be created through the mix of multiple spatial scales.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was a large, randomized controlled trial of cancer screening that also evolved over time into a unique epidemiologic cohort. Vast quantities of data have been collected since the beginning of the trial in 1993. Screening data was obtained through 2006. Questionnaire-based risk factor data (collected at baseline and at other points in the trial), vital status, cancer diagnoses and treatment, biospecimen data and additional ancillary efforts continue to be collected. Accurate data collection and efficient management methods are required to ensure high-quality data and valid and consistent analyses of trial outcomes. Information Management Services (IMS) was and continues to be responsible for processing and converting the collected raw PLCO data into comprehensive and accessible datasets. IMS also continues to provide a wide spectrum of analytic support including support for trial monitoring, data sharing, and epidemiologic research. In this paper, we describe the data processing and management requirements from the analytic team perspective, highlighting the various data sources and their complexity. We also illustrate the construction of usable analytic data files and discuss the wide range of analytic support provided. Instructions for accessing PLCO data also are provided.

The most rigorous and accurate approach to evaluating clinical events in cancer screening studies is to use data obtained through medical record abstraction (MRA). Although MRA is complex, the particulars of the procedure-such as the specific training and quality assurance processes, challenges of implementation, and other factors that influence the quality of abstraction--are usually not described in reports of studies that employed the technique. In this paper, we present the details of MRA activities used in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which used MRA to determine primary and secondary outcomes and collect data on other clinical events. We describe triggers of the MRA cycle and the specific tasks that were part of the abstraction process. We also discuss training and certification of abstracting staff, and technical methods and communication procedures used for data quality assurance. We include discussion of challenges faced and lessons learned.

Biomedical research cannot succeed without funding, knowledgeable staff, and appropriate infrastructure. There are however equally important but intangible factors that are rarely considered in planning large multidisciplinary endeavors or evaluating their success. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial required extensive collaborations between individuals from many fields, including clinicians, clinical trialists, and administrators; it also addressed questions across the spectrum of cancer prevention and control. In this manuscript, we examine the experiences and opinions of trial staff regarding the building of successful relationships in PLCO. We summarize, in narrative form, data collected using open-ended questionnaires that were administered to the National Cancer Institute project officers, coordinating center staff, screening center principal investigators, and screening center coordinators in 2015, about 3 years after publication of the final primary trial manuscript. Trust, respect, listening to others, and in-person interaction were frequently mentioned as crucial to building successful relationships.

It is imperative to measure the degree of contamination throughout the course of randomized controlled trials, as contamination, the receipt of the intervention arm regimen by control arm participants, can affect trial power. In the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, contamination was estimated through use of the self-administered Health Status Questionnaire (HSQ) annually to a randomly-selected subset of control arm participants. We examined agreement of self-report of chest x-ray on the HSQ with clinic records at one of the 10 PLCO screening centers (Henry Ford Health System, or HFHS). We focus on HFHS participants covered by the Health Alliance Plan (HAP), a managed health care insurance plan owned and operated by HFHS, because claims for care received both at HFHS and other facilities are available in HFHS databases for HAP enrollees. We examined agreement for the six years prior to HSQ completion, with HFHS clinic records considered to be the gold standard. For those who had complete HAP coverage during the six years, percent agreement was 0.69, sensitivity was 0.84, and positive predictive value was 0.76. Specificity and negative predicted value were low, however (0.28 and 0.38, respectively), and Cohen's kappa was 0.13. For groups with incomplete or no HAP coverage, and when timing of exam was considered, performance measures typically became lower, in some instances below 0.20. These data suggest that self-report of chest x-ray screening may not be accurate, although high prevalence of chest x-ray may make performance measures less interpretable.