bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A54: Case-based causality: An application of artificial intelligence to environmental carcinogenesis
Authors: Weed Douglas L. 
Published: June 2022

Abstract
Determining whether environmental exposures cause cancer is a complex and often controversial issue, involving epidemiologic and toxicologic studies and a family of methods discussed and debated for decades. These methods include the general scientific method, study design and statistical methods, and research synthesis methods—sometimes called “weight of evidence” methods—such as the systematic narrative review, meta-analysis, and criteria-based methods of causation. These methods have been applied to a wide range of topics involving environmental (and occupational and lifestyle) exposures as well as a wide variety of specific cancers. The purpose of this project is to bring a method from artificial intelligence (AI)—Case-Based Reasoning (CBR)—to bear on the issue of environmental causes of cancer. Case-Based Reasoning is an AI method that capitalizes upon past experience to solve current problems. In terms of the search for causes of disease, CBR (renamed Case-Based Causality) is a method that uses bodies of evidence from past examples of known causal relationships to inform the determination of causality for a body of evidence associated with an exposure-disease relationship under investigation. CBR is typically described at its conceptual level in terms of 5 “Rs”: Representation, Retrieval, Reuse, Revision, and Retention. Each “R” can be interpreted in terms of the causation issue in epidemiology and public health. “Representation,” for example, is the collection, description, summarization, and interpretation of a body of evidence regarding an exposure and a disease—what is basically provided by a high-quality systematic narrative review, which may include a meta-analysis. In this presentation, the 5 “Rs” of Case-Based Causality (CBC) will be described and applied to current issues in environmental carcinogenesis. In addition, the relationship of CBC to existing methods of causal inference will be noted as well as the links between CBC and the concept of reliability, i.e., the extent to which current methods of causal inference provide reproducible results. Fundamentally, Case-Based Causality is a method for examining whether a body of evidence under investigation can be considered causal by examining the extent to which its characteristics are similar to bodies of evidence from known (i.e., established) causal relationships.
Citation Format: Douglas L. Weed. Case-based causality: An application of artificial intelligence to environmental carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A54.
Abstract IA13: Key characteristics of carcinogens
Authors: Smith Martyn T. 
Published: June 2022

Abstract
The key characteristics (KCs) of human carcinogens were recently introduced as the basis of a uniform approach for searching, organizing, and evaluating mechanistic evidence to support cancer hazard identification (Smith et al., 2016; Guyton et al., 2018). The KCs comprise the properties of known human carcinogens, including their ability to be genotoxic, be immunosuppressive, or modulate receptor-mediated effects. Established human carcinogens commonly exhibit one or more of these characteristics, and therefore, data on these characteristics can provide independent evidence of carcinogenicity when human data are lacking. Such data can also help in interpreting the relevance and importance of findings of cancer in animals and in humans. In its 2017 report, “Using 21st Century Science to Improve Risk-Related Evaluations,” the NRC recently opined that the KCs approach “avoids a narrow focus on specific pathways and hypotheses and provides for a broad, holistic consideration of the mechanistic evidence.” They further suggested that key characteristics be developed for other endpoints, such as endocrine disruption and reproductive toxicity, and efforts in this regard are approaching completion and publication. The KC approach therefore holds great potential to improve hazard identification and risk assessment but still needs to be further developed, especially in regard to its integration with the hallmarks of cancer and its potential for helping analyze the toxic effects of untested chemicals and chemical mixtures in cell culture and experimental animals. Unfortunately, the current Tox21 and Toxcast repertoire of assays is mostly lacking in relevance to the KCs, as are most clinical biomarkers. Approaches to developing a new set of high-throughput tests and biomarkers (a CarciCAST) will be described along with a discussion of the use of the key characteristics approach in hazard identification and risk assessment instead of, or as well as, the current MOA/AOP approach.
References
Guyton KZ, Rusyn I, Chiu WA, Corpet DE, van den Berg M, Ross MK, et al. Application of the key characteristics of carcinogens in cancer hazard identification. Carcinogenesis 2018;39:614-22; doi:10.1093/carcin/bgy031.
Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, et al. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 2016;124:713-21; doi:10.1289/ehp.1509912.
Citation Format: Martyn T. Smith. Key characteristics of carcinogens [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA13.
Abstract IA17: Challenges and opportunities in environmental carcinogenesis: The NIEHS perspective
Authors: Woychik Richard 
Published: June 2022

Abstract
The National Institute of Environmental Health Sciences (NIEHS) embraces a mission to understand how the environment influences a wide range of health outcomes, but cancer has been a major focus of the Institute’s work since its early days. Last year, NIEHS published a new iteration of its strategic plan, streamlining its work into three interrelated themes: advancing environmental health sciences; translating those advances from data to knowledge to action; and supporting the training, processes, partnerships, and infrastructure to make the mission possible. “Advancing environmental health sciences” includes studying not just effects of acute exposures, but also of chronic low level exposures to environmental agents that happen over time; discovering the mechanisms that govern susceptibility during different time periods over the lifespan; understanding the effects of exposure to complex real-world mixtures or even of the full exposome; and most recently, learning about how environmental exposures can impact health and cancer outcomes by changing the microbiome in the gut. All these research areas are key components to understanding how factors in the environment can impact carcinogenesis. Additionally, the institute has embraced new advances to study how genetic and epigenetic variability in the host impacts carcinogenesis. For example, use of the Diversity Outcross resource of outbred mice provides an opportunity to overcome the difficulties inherent in using genetically uniform inbred strains of mice to understand genetic susceptibility to environmental carcinogens. Another exciting direction for the Institute is the use of archived tumor tissues from the National Toxicology Program to determine whether there are specific mutagenic signatures associated with different environmental agents. Along these lines, the Institute collaborated with Agilent to develop the first rat exome probe set that is being used to sequence the exons from material derived from FFPE samples. This research was supported by the NIH, National Institute of Environmental Health Sciences.
Citation Format: Richard Woychik. Challenges and opportunities in environmental carcinogenesis: The NIEHS perspective [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA17.
Abstract IA19: A compendium of mutational signatures due to environmental exposures
Authors: Nik-Zainal Serena 
Published: June 2022

Abstract
Whole-genome sequencing of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 whole-genome sequences of human-induced pluripotent stem cells (iPSCs) following exposure to known or suspected environmental carcinogens. 79 agents were tested with or without metabolic activation at concentrations that produced measurable cytotoxicity; 41 yielded characteristic substitution mutational signatures that, in some cases, exhibit similarity with signatures found in human tumors. Additionally, 6 agents produced double-substitution signatures and 8 also produced indel signatures. Investigating mutation distribution asymmetries across genome topography reveals fully functional mismatch and transcription-coupled repair pathways in iPSCs. Primary adducts induced by environmental carcinogens can be resolved by disparate repair/replicative pathways, resulting in an assortment of signature outcomes even for a single mutagen. This compendium of experimentally induced mutational signatures permits further exploration of roles of environmental agents in cancer etiology, and underscores how human stem cell DNA is directly vulnerable to environmental agents.
Citation Format: Serena Nik-Zainal. A compendium of mutational signatures due to environmental exposures [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA19.
Abstract PR04: Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water
Authors: Temkin Alexis , Evans Sydney , Manidis Tatiana , Campbell Chris , Naidenko Olga V. 
Published: June 2022

Abstract
Background: Nitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States.
Methods: This study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk.
Results: On the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2,939 cases of very low birth weight, 1,725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2,300 to 12,594 annual nitrate-attributable cancer cases (mean: 6,537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of $250 million to $1.5 billion U.S. dollars, together with a potential $1.3 to $6.5 billion impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water.
Conclusion: Health and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases.
This abstract is also being presented as Poster A44.
Citation Format: Alexis Temkin, Sydney Evans, Tatiana Manidis, Chris Campbell, Olga V. Naidenko. Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR04.
Understanding Errors in Cloud Liquid Water Path Retrievals Derived from CloudSat Path-Integrated Attenuation
Authors: Lebsock Matthew , Takahashi Hanii , Roy Richard , Kurowski Marcin J. , Oreopoulos Lazaros 
Published: June 2022

Abstract
An algorithm that derives the nonprecipitating cloud liquid water path Wcld from CloudSat using a surface reference technique (SRT) is presented. The uncertainty characteristics of the SRT are evaluated. It is demonstrated that an accurate analytical formulation for the pixel-scale precision can be derived. The average precision of the SRT is estimated to be 34 g m−2 at the individual pixel scale; however, precision systematically decreases from around 30 to 40 g m−2 as cloud fraction varies from 0% to 100%. The retrievals of clear-sky Wcld have a mean bias of 0.9 g m−2. Output from a large-eddy simulation coupled to a radar simulator shows that an additional bias of −8% may result from nonuniformity within the footprint of cloudy pixels. The retrieval yield for the SRT, measured relative to all warm clouds over ocean between 60°N and 60°S latitude is 43%. The SRT Wcld is compared with one estimate of Wcld from the Moderate Resolution Imaging Spectroradiometer (MODIS) using an adiabatic cloud profile and an effective radius derived from 3.7-μm reflectance. A strong correlation between the mean MODIS Wcld and SRT Wcld is found across diverse cloud regimes, but with biases in the mean Wcld that are cloud-regime dependent. Overall, the mean bias of the SRT relative to MODIS is −13.1 g m−2. Systematic underestimates of Wcld by the SRT resulting from nonuniform beamfilling cannot be ruled out as an explanation for the retrieval bias.
A Generalized Dual-Frequency Ratio (DFR) Approach for Rain Retrievals
Authors: Meneghini Robert , Liao Liang , Iguchi Toshio 
Published: June 2022

Abstract
The dual-frequency ratio of radar reflectivity factors (DFR) has been shown to be a useful quantity as it is independent of the number concentration of the particle size distribution and primarily a function of the mass-weighted particle diameter Dm. A drawback of DFR-related methods for rain estimation, however, is the nonunique relationship between Dm and DFR. At Ku- and Ka-band frequencies, two solutions for Dm exist when DFR is less than zero. This ambiguity generates multiple solutions for the range profiles of the particle size parameters. We investigate characteristics of these solutions for both the initial-value (forward) and final-value (backward) forms of the equations. To choose one among many possible range profiles of Dm, number concentration, and rain rate R, independently measured path attenuations are used. For the backward approach, the possibility exists of dispensing with externally measured path attenuations by achieving consistency between the input and output path attenuations. The methods are tested by means of a simulation based on disdrometer-measured raindrop size distributions and the results are compared with a simplified version of the operational R–Dm method.
Effects of Free Trade Agreements on Trade Activities of Signatory Countries
Authors: Gurtu Amulya , Johny Jestin , Chowdhary Rupal 
Published: June 2022

The study analyses the effects of free trade agreements (FTAs) signed by India on the changes in the trade volumes of member states. The article analyses the benefits of the economic integration of export earnings to meet the import demands. It is found that FTAs improve economic activities among the signing countries. This article highlights the role of FTAs in the economic activities of countries signing the trade agreement. Post FTAs, the compound annual growth rate (CAGR) of exports increased and imports reduced. This research will help researchers identify the areas and countries where FTAs are desirable and help improve economic activities. JEL Codes: F15
ETS1 is a novel transcriptional regulator of adult T-cell leukemia/lymphoma of North American descent
Authors: Luchtel Rebecca A. , Zhao Yongmei , Aggarwal Ritesh K. , Pradhan Kith , Maqbool Shahina B. 
Published: June 2022

Abstract
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell lymphoma associated with the human T-cell lymphotropic virus type 1 virus endemic in regions including Japan, the Caribbean islands, and Latin America. Although progress has been made to understand the disease, survival outcomes with current standard therapy remain extremely poor particularly in acute ATLL, underlying the need for better understanding of its biology and identification of novel therapeutic targets. Recently, it was demonstrated that ATLL of North American–descendent patients (NA-ATLL) is both clinically and molecularly distinct from Japanese-descendent (J-ATLL), with inferior prognosis and higher incidence of epigenetic-targeting mutations compared with J-ATLL. In this study, combined chromatin accessibility and transcriptomic profiling were used to further understand the key transcriptional regulators of NA-ATLL compared with J-ATLL. The ETS1 motif was found to be enriched in chromatin regions that were differentially open in NA-ATLL, whereas the AP1/IRF4 motifs were enriched in chromatin regions more open in J-ATLL. ETS1 expression was markedly elevated in NA-ATLL in both cell line and primary tumor samples, and knockdown of ETS1 in NA-ATLL cells resulted in inhibition of cell growth. CCR4, a previously identified oncogenic factor in ATLL, was found to be a direct ETS1 transcriptional target in NA-ATLL. As such, ETS1 provides an alternate mechanism to enhance CCR4 expression/activity in NA-ATLL, even in the absence of activating CCR4 mutations (CCR4 mutations were identified in 4 of 9 NA-ATLL cases). Taken together, this study identifies ETS1 as a novel dominant oncogenic transcriptional regulator in NA-ATLL.
Modeling and Parameter Sensitivity Analysis of Valve-Controlled Helical Hydraulic Rotary Actuator System
Authors: Zhang Kun , Zhang Junhui , Gan Minyao , Zong Huaizhi , Wang Ximeng , Huang Hsinpu , Su Qi , Xu Bing 
Published: June 2022

AbstractAs a type of hydraulic rotary actuator, a helical hydraulic rotary actuator exhibits a large angle, high torque, and compact structure; hence, it has been widely used in various fields. However, its core technology is proprietary to several companies and thus has not been disclosed. Furthermore, the relevant reports are primarily limited to the component level. The dynamic characteristics of the output when a helical rotary actuator is applied to a closed-loop system are investigated from the perspective of driving system design. Two main aspects are considered: one is to establish a reliable mathematical model and the other is to consider the effect of system parameter perturbation on the output. In this study, a detailed mechanical analysis of a helical rotary hydraulic cylinder is first performed, factors such as friction and load are considered, and an accurate dynamic model of the actuator is established. Subsequently, considering the nonlinear characteristics of pressure flow and the dynamic characteristics of the valve, a dynamic model of a valve-controlled helical rotary actuator angle closed-loop system is described based on sixth-order nonlinear state equations, which has never been reported previously. After deriving the system model, a sensitivity analysis of 23 main parameters in the model with a perturbation of 10% is performed under nine operating conditions. Finally, the system dynamics model and sensitivity analysis results are verified via a prototype experiment and co-simulation, which demonstrate the reliability of the theoretical results obtained in this study. The results provide an accurate mathematical model and analysis basis for the structural optimization or control compensation of similar systems.
Radiographer-led discharge for emergency care patients, requiring projection radiography of minor musculoskeletal injuries: a scoping review
Authors: Shepherd Jenny , Lourida Ilianna , Meertens Robert M. 
Published: June 2022

Abstract
Background
Pressure on emergency departments (EDs) from increased attendance for minor injuries has been recognised in the United Kingdom. Radiographer-led discharge (RLD) has potential for improving efficiency, through radiographers trained to discharge patients or refer them for treatment at the point of image assessment. This review aims to scope all RLD literature and identify research assessing the merits of RLD and requirements to enable implementation.

Methods
We conducted a scoping review of studies relating to RLD of emergency care patients requiring projection radiography of minor musculoskeletal (MSK) injuries. MEDLINE, Embase and CINAHL, relevant radiography journals and grey literature were searched. Articles were reviewed and the full texts of selected studies were screened against eligibility criteria. The data were extracted, collated and a narrative synthesis completed.

Results
Seven studies with varying study designs were included in the review. The small number of studies was possibly due to a generally low research uptake in radiography. The main outcome for four studies was reduced length of stay in ED, with recall and re-attendance to ED a primary outcome in one study and secondary outcome for two other studies. The potential for increased efficiency in the minor MSK pathway patient pathway and capacity for ED staff was recognised. Radiographers identified a concern regarding the risk of litigation and incentive of increased salary when considering RLD. The studies were broadly radiographer focussed, despite RLD spanning ED and Radiology.

Conclusion
There were a low number of RLD active radiographers, likely to be motivated individuals. However, RLD has potential for generalisability with protocol variations evident, all producing similar positive outcomes. Understanding radiography and ED culture could clarify facilitators for RLD to be utilised more sustainably into the future. Cost effectiveness studies, action research within ED, and cluster randomised controlled trial with process evaluation are needed to fully understand the potential for RLD.
The cost effectiveness of RLD may provide financial support for training radiographers and increasing their salary, with potential future benefit of reduction in workload within ED. RLD implementation would require an inter-professional approach achieved by understanding ED staff and patient perspectives and ensuring these views are central to RLD implementation.