bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract SY06-03: Reprogramming the tumor microenvironment to improve responses to therapy
Authors: Denardo David G.
Published: July 2017

Immunotherapeutics represent highly promising agents with the potential to improve patient outcomes in a variety of cancer types. Unfortunately, single-agent immunotherapy has achieved limited clinical benefit to date in patients suffering from pancreatic ductal adenocarcinoma (PDAC). This may be due to the presence of a uniquely immunosuppressive tumor microenvironment (TME) present in PDACs, which creates a barrier to effective immune surveillance. Critical obstacles to immunotherapy in PDAC tumors include the dense desmoplastic stroma that acts as a barrier to T-cell infiltration and the high numbers of tumor-associated immunosuppressive cells. We have identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as a significant regulator of the fibrotic and immunosuppressive TME. We found that FAK activity was elevated in human PDAC tissues and correlates with high levels of fibrosis and poor CD8+ cytotoxic T-cell infiltration. Single-agent FAK inhibition (VS-4718) significantly limited tumor progression, resulting in a doubling of survival in the p48-Cre/LSL-KrasG12D/p53Flox/+ (KPC) mouse model of human PDAC. This alteration in tumor progression was associated with dramatically reduced tumor fibrosis, decreased numbers of tumor-infiltrating immature myeloid cells, and immunosuppressive macrophages. We postulated that these desirable effects of FAK inhibition on the TME might render PDAC tumors more sensitive to immunotherapy. Accordingly, we found that FAK inhibition rendered the previously unresponsive KPC mouse model responsive to anti-PD1 and anti-CTLA4 antagonists, leading to a near tripling of survival times. These data suggest that FAK inhibition increases immune surveillance by overcoming the fibrotic and immunosuppressive PDAC TME and thus renders tumors responsive to immunotherapy. To test this hypothesis in human PDAC patients, we have opened a phase I clinical trial testing the safety and impact on the tumor microenvironment of the FAK inhibitor defactinib, in combination with pembrolizumab and gemcitabine (NCT02546531). These studies are ongoing in patients with advanced cancer, including metastatic PDAC. Early biomarker studies on PDAC tissue collected pre- and post-therapy suggest that this combination impacts the immunosuppressive TME.

Citation Format: David G. Denardo. Reprogramming the tumor microenvironment to improve responses to therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY06-03. doi:10.1158/1538-7445.AM2017-SY06-03
Abstract SY07-02: Adipose stromal cells: A player in cancer progression and a therapeutic target
Authors: Kolonin Mikhail
Published: July 2017

Prostate cancer (PCa) is promoted by white adipose tissue (WAT) overgrown in obesity. As an underlying mechanism, we have discovered the recruitment of adipose stromal cells (ASC) by tumors. We reported that CXCL1 expressed by cancer cells chemoattracts ASC expressing its receptor CXCR1. As a candidate upstream mechanism, we identified interleukin 22 secreted by WAT-infiltrating leukocytes and signaling through IL-22R in cancer cells. Our experiments in Hi-Myc mice indicate that obesity promotes epithelial-mesenchymal transition (EMT). We show that ASC directly induce EMT in adenocarcinoma cells. To test whether cancer progression can be blocked by ASC targeting, we have used a hunter-killer peptide D-WAT composed of an ASC-homing and a pro-apoptotic domain. D-WAT administration depleted prostate stromal cells expressing a chemokine SDF1α and suppressed the EMT. Our results indicate that ASC promote the EMT, at least in part, via SDF1a paracrine signaling and validate ASC as a therapeutic target.

Citation Format: Mikhail Kolonin. Adipose stromal cells: A player in cancer progression and a therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY07-02. doi:10.1158/1538-7445.AM2017-SY07-02
Abstract SY09-02: A novel genetic mechanism of evading antitumor immunity in multiple human cancers
Authors: Ogawa Seishi
Published: July 2017

Immune checkpoint blockade therapy using antibodies against programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) is revolutionizing cancer treatment. Surprising therapeutic responses to these agents are obtained in many advanced cancer patients with different tumor types, such as melanoma, non-small-cell lung cancer, kidney cancer, and Hodgkin lymphoma, suggesting that cancer cells depend critically on evading immune surveillance for their malignant growth. Accumulating evidence suggests that these antibodies convey their therapeutic effects through targeting the PD-1/PD-L1 immune checkpoint to unleash antitumor immune responses. However, the genetic basis for the PD-1/PD-L1-mediated immune escape has not been fully elucidated, with the exception of enhanced PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, which were reported in Hodgkin and other B-cell lymphomas as well as stomach adenocarcinoma. Only a few genetic markers are currently available to reliably predict response to anti-PD-1/PD-L1 therapy as well. I will show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3′ region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3′-untranslated region (UTR). Disruption of Pd-l1 3′-UTR in mice enables immune evasion of EG7-OVA tumor cells with elevated PD-L1 expression in vivo, which is effectively inhibited by PD-1/PD-L1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3′-UTR disruption could serve as a genetic marker to identify cancers that actively evade antitumor immunity through PD-L1 overexpression.

Citation Format: Seishi Ogawa. A novel genetic mechanism of evading antitumor immunity in multiple human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY09-02. doi:10.1158/1538-7445.AM2017-SY09-02
Abstract SY19-03: Inflammation-driven cancer: Host and microbial pathways
Authors: Powrie Fiona , McCuaig Sarah , West Nathan , Ryzhakov Grigory
Published: July 2017

The gastrointestinal (GI) tract is home to a large number and vast array of bacteria that play an important role in nutrition, immune system development, and host defense. In inflammatory bowel disease (IBD) there is a breakdown in this mutualistic relationship, resulting in aberrant inflammatory responses that can progress to colon cancer. Our studies in model systems have implicated innate lymphoid cells and production of IL-22 as key drivers of neoplasia and cancer in the intestine. In this presentation I will discuss new checkpoints that control bacteria-driven innate inflammation in the intestine as well as the functional effects of IL-22 on intestinal epithelial cells and interactions between IL-22 signaling and oncogenic mutations. Further understanding of the interactions between host genetics, gut microbiota, and deranged inflammatory pathways will yield new approaches to patient stratification and personalized therapy.

Citation Format: Fiona Powrie, Sarah McCuaig, Nathan West, Grigory Ryzhakov. Inflammation-driven cancer: Host and microbial pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY19-03. doi:10.1158/1538-7445.AM2017-SY19-03
Abstract SY21-03: Cancer evolution as a therapeutic target
Authors: Bardelli Alberto
Published: July 2017

When metastatic cancers are challenged with targeted agents, almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? Addressing this question means considering as a target not “only” individual oncogenes but also the evolving nature of human tumors. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumor’s evolution, the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells; that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. Another approach is to unleash the ability of the immune system to recognize drug-resistant cells. We tested this possibility in syngeneic mouse models of CRC sensitive to targeted therapies. Our findings indicate that manipulation of the mutational loads can trigger prolonged therapeutic responses that are not observed when cancer cells are challenged with targeted drugs alone. We postulate that rationally combined targeted therapies and immunotherapies can restrain tumor evolution and can limit the emergence of drug resistance, thus leading to long-term responses.

Citation Format: Alberto Bardelli. Cancer evolution as a therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY21-03. doi:10.1158/1538-7445.AM2017-SY21-03
Abstract SY23-01: KSHV: Immune evasion and oncogenesis
Authors: Damania Blossom A.
Published: July 2017

Infection of cells with oncogenic DNA viruses, including herpesviruses, triggers innate immune responses mediated by DNA sensors. Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that upon activation produces the cyclic dinucleotide cGAMP, which binds and activates Stimulator of Interferon Genes (STING), leading to interferon production and an antiviral response. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked to several human malignancies including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). We have found that KSHV infection activates the cGAS-STING pathway and that cGAS and STING also play an important role in regulating KSHV reactivation from latency. Furthermore, we have identified several KSHV viral proteins that inhibit the cGAS-STING pathway. It appears that modulation of this pathway is important for viral transmission and the lifelong persistence of oncogenic herpesviruses in the human population.

Citation Format: Blossom A. Damania. KSHV: Immune evasion and oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY23-01. doi:10.1158/1538-7445.AM2017-SY23-01
Abstract SY28-02: The adipose-cancer link: From microenvironment to metabolomics
Authors: Ulrich Cornelia M.
Published: July 2017

This presentation will showcase the interface of systemic and localized disturbances in metabolism with tumor development, specifically focusing on colorectal cancer. Colorectal cancer is the second leading cause of cancer-related death worldwide among both men and women. Risk and preventive factors are well established and include, among others, lack of physical activity and obesity (risk) as well as aspirin use and screening (prevention). Adipose tissue is emerging as a key player in carcinogenesis through the secretion of proinflammatory cytokines and adipokines. The colon is surrounded by adipose tissue, which supports the direct (paracrine) adipose-colon crosstalk and influence as a tumor microenvironment, as well as systemic influences on colon carcinogenesis factors secreted into the bloodstream. As part of the ColoCare cohort, an international, multicenter cohort of colorectal cancer patients, we have investigated adipose tissue distribution, composition, characteristics, and possible influence on colorectal tumors. In an integrated analysis of the transcriptome and metabolome of visceral and subcutaneous adipose tissue (VAT and SAT, respectively), we showed that there are distinct differences that may play a central role in driving carcinogenesis (1). These analyses are ongoing and have been extended to blood-based measures of the inflammasome and metabolome, as well as tumor characteristics. Adipose tissue biology can also be directly affected by weight-loss interventions through diet and exercise. As part of the Nutrition and Exercise in Women (NEW) study, we showed that weight loss results in changes in adipose tissue gene expression as well as corresponding reductions in biomarkers, including inflammatory biomarkers (2, 3).

References

1. Liesenfeld DB, Grapov D, Fahrmann JF, Salou M, Scherer D, Toth R, et al. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. Am J Clin Nutr 2015;102(2):433-43.

2. Imayama I, Ulrich CM, Alfano CM, Wang C, Xiao L, Wener MH, et al. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial. Cancer Res 2012;72(9):2314-26.

3. Campbell KL, Foster-Schubert KE, Makar KW, Kratz M, Hagman D, Schur EA, et al. Gene expression changes in adipose tissue with diet- and/or exercise-induced weight loss. Cancer Prev Res 2013;6(3):217-31.

Citation Format: Cornelia M. Ulrich. The adipose-cancer link: From microenvironment to metabolomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY28-02. doi:10.1158/1538-7445.AM2017-SY28-02
Abstract SY29-01: Targeting DNA repair factor dysfunction in advanced prostate cancer
Authors: Knudsen Karen E.
Published: July 2017

Prostatic adenocarcinoma (PCa) is the third leading cause of cancer death in U.S. men. Organ-confined PCa can be effectively managed, but there is no durable treatment for advanced disease. Advanced PCa is treated through androgen deprivation therapy, often coupled with direct androgen receptor (AR) antagonists, as PCa is exquisitely dependent on AR activity for cell survival and proliferation. Unfortunately, relapse is common; recurrent disease arises largely due to resurgent AR activity with 2-3 years, and there is no cure for this castration-resistant phase (castration-resistant PCa; CRPC). Thus, there is a significant need to develop new means for targeting recurrent AR activity or to develop adjuvant therapies in advanced PCa. Emerging data from our laboratory and others strongly support the concept that alterations in DNA damage repair (DDR) pathways are more common than previously thought in sporadic PCa, and that alterations in these pathways may afford new, more effective means of therapeutic intervention. New studies to be discussed will address underlying mechanisms of action with regard to the pathway and identify clinically actionable ramifications of DNA repair dysfunction. Major concepts to be considered include 1) new findings implicating differential functions of p53 somatic mutations on PCa behavior and response to therapeutic intervention and 2) differential roles of DNA-dependent protein kinase (DNAPK) in controlling PCa progression. Findings to be discussed strongly support a model wherein selected DDR pathways can be developed as therapeutic targets to tailor treatment for prostate cancer and improve outcome for advanced disease.

Citation Format: Karen E. Knudsen. Targeting DNA repair factor dysfunction in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY29-01. doi:10.1158/1538-7445.AM2017-SY29-01
Abstract SY32-04: About Chomsky, patterns, and noncoding RNAs cancer therapeutics
Authors: Calin George A.
Published: July 2017

Resistance to therapy is an important issue in the treatment of cancer, responsible for many cancer-related deaths. Despites decades of research into overcoming this resistance, only modest advances have been made and the resistance mechanisms remain poorly understood. Although to date the most studied noncoding RNAs (ncRNAs) are miRNAs, the importance of long noncoding RNAs (lncRNAs) in cancer is increasingly being recognized. Here we summarize the roles of miRNAs and lncRNAs in cancer, with a focus on the recently identified novel mechanisms of action, and discuss the current strategies in designing ncRNA-targeting therapeutics, as well as the associated challenges. We are further presenting a novel strategy to identify new therapeutic ncRNA targets by using Chomsky-type grammars based on combinatorial use of coding and noncoding RNAs.

Citation Format: George A. Calin. About Chomsky, patterns, and noncoding RNAs cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY32-04. doi:10.1158/1538-7445.AM2017-SY32-04
Palaemonella shirakawai, a new species of shrimp (Crustacea: Decapoda: Palaemonidae), associated with burrow dwelling opistognathid fish from the Ryukyu Islands, Japan
Authors: OKUNO JUNJI
Published: July 2017

A new palaemonid shrimp, Palaemonella shirakawai sp. nov., is described and illustrated on the basis of a single ovigerous female specimen captured from the Ryukyu Islands, Japan. It appears closest to P. aliska Marin by sharing the median carina of the carapace armed with dorsal rostral teeth extending posterior to the level of the hepatic tooth, but is immediately differentiated by the shorter rostrum, a rounded posterior margin of the telson, an elongate antennal scaphocerite with a truncate distal margin of lamella, and the longer second pereiopod. The present new species is an associate of burrow dwelling fishes belonging to the family Opistognathidae.
Description of Limyra, new genus with a new species and the redescription of Cibyra pluriargenteus (Viette), from southeastern Brazil (Lepidoptera: Hepialidae)
Authors: MIELKE CARLOS G. C. , DELL’ERBA RAFAEL , DUARTE MARCELO
Published: July 2017

Cibyra pluriargenteus (Viette, 1955) is redescribed and both sexes are figured for the first time. The new monotypic genus Limyra, gen. nov., (Lepidoptera, Hepialidae) is erected to include L. silvai sp. nov. from São Paulo state, southeastern Brazil. The male genitalia are diagnostic for the genus. The male holotype is deposited in the collection of the Museu de Zoologia, São Paulo, São Paulo, Brazil.
Further Improvement of the Heavy Orographic Rainfall Retrievals in the GSMaP Algorithm for Microwave Radiometers
Authors: Yamamoto Munehisa K. , Shige Shoichi , Yu Cheng-Ku , Cheng Lin-Wen
Published: July 2017

An orographic/nonorographic rainfall classification scheme has been introduced for the operational algorithm of the Global Satellite Mapping of Precipitation (GSMaP) for passive microwave radiometers. However, problems of overestimations and false alarms of heavy orographic rainfall remain unresolved. This is because the current scheme selected lower constant thresholds of orographic rainfall conditions for global application and used values of orographically forced upward motion w derived from near-surface atmospheric data. This study improves the conceptual model of the warm-rain process for considering the strength of the upstream flow of the low-level troposphere. Under a weak upstream current, rain reaches the foothills of the windward mountain slope because of sufficient time for condensation and precipitation enhancement by the topography. Conversely, under a strong upstream current, precipitation enhancement occurs nearer to the mountain peak. This is because the upstream current flows so quickly that there is insufficient time for enhancement of precipitation over the foothills of the windward mountain slope. After implementing a variable threshold for w that depends on the mean horizontal low-level wind, the area of orographic enhancement of rain was detected reasonably well in cases of both strong and weak winds. To improve the accuracy of estimates of orographic rainfall, an adjustment to the rain estimation was introduced using a lower-frequency channel. The biases of the rainfall estimate for the adjusted scheme from the Tropical Rainfall Measuring Mission Precipitation Radar were improved for the cases considered here as well as for the Asian region of heavy orographic rainfall over land.
Recent Changes in U.S. Regional Heat Wave Characteristics in Observations and Reanalyses
Authors: Schoof J. T. , Ford T. W. , Pryor S. C.
Published: July 2017

Humidity is a key determinant of heat wave impacts, but studies investigating changes in extreme heat events have not differentiated between events characterized by high temperatures and those characterized by simultaneously elevated temperature and humidity. The authors present a framework, using air temperature (T) and equivalent temperature (TE; a measure combining temperature and specific humidity), to examine changes in local percentile-based extreme heat events characterized by high temperature (T only) and those with high temperature and humidity (T-and-TE events). Application to one observational dataset (PRISM), four reanalysis products (1981–2015), and seven U.S. regions reveals widespread changes in heat wave characteristics over the 35-yr period. Agreement among the datasets employed on several heat wave metrics suggests that many of the findings are robust. With the exception of the northern plains region, all regions experienced increases in both T-only and T-and-TE heat wave day (HWD) frequency in each of the reanalyses. In the northern plains, all datasets have negative trends in T-only HWD frequency and positive trends in T-and-TE HWD frequency. Trends in HWD frequency were generally accompanied by changes in the spatial footprint in heat wave conditions. Temperature has increased significantly during T-only HWDs in the western regions, while increases in TE during T-and-TE HWDs have occurred in the central United States and Northeast region. These findings suggest that equivalent temperature provides an alternative perspective on the evolution of regional heat wave climatology. Studies considering changes in regional heat wave impacts should carefully consider the role of atmospheric moisture.
Toward Understanding Trust: A Response to Adams and Miskell
Authors: Romero Lisa S. , Mitchell Douglas E.
Published: July 2017

Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of Educational Administration Quarterly, C. M. Adams and Miskell argued that their Teacher Trust of District Administration Scale provided evidence that trust is a single factor that cannot be unpacked, and that our three-factor theory of trust, which asserts that trust involves the discernment of benevolence, competence, and integrity, is invalid. We find multiple conceptual and methodological flaws in their reasoning. Method/Approach: We analyze data provided by C. M. Adams and Miskell that were used in their original 2016 article. The data set includes responses from 606 teachers in 72 schools to the 10 survey questions that comprise the Teacher Trust of District Administration Scale. We reproduce and critique the results of four models presented, and corrected, by C. M. Adams and Miskell, and present an alternative second-order model of trust with three first-order factors representing benevolence, competence, and integrity. Findings and Implications: Consistent with theory, we find that trust is more appropriately modeled as a multifactor construct. A multifactor model of trust is not merely an advance in measurement, it has important, actionable implications for research and practice. Measuring trust as a second-order factor, with first-order factors benevolence, competence, and integrity, positions us to make more nuanced judgements about trust, more easily diagnose problems, and prescribe interventions needed to develop, maintain, or repair trust in schools.
“DROPPING THE BALL”: The Understudied Nexus of Sports and Politics
Authors: Gift Thomas , Miner Andrew
Published: July 2017

From the Roman Colosseum to the Yankee Stadium, the Olympics to the Super Bowl, sports have always played a central role in societies. With so much at stake—money, pride, power (and occasionally even fun)—sports are undeniably political. Yet despite this recognition, political scientists and policy scholars devote little attention to the study of sports, especially compared with other disciplines like business, law, and economics. We offer reasons for this void and suggest how political scientists can begin to fill it. In our view, the nexus between sports and politics is not only a vital topic of study on its own, but it can also provide a lens through which to examine—and test—broader questions in the discipline. We propose how scholars can think more systematically about the interaction of politics and sports and leverage the distinctive qualities of sports to improve causal identification across a range of issue areas and subfields in political science and policy studies.
Sex-related differences in bronchial parameters and pulmonary function test results in patients with chronic obstructive pulmonary disease based on three-dimensional quantitative computed tomography
Authors: Li Yan , Dai Yong-liang , Yu Nan , Guo You-min
Published: July 2017

Objective

This study was performed to evaluate the effect of sex on bronchial parameters and the predicted forced expiratory volume in 1 s expressed as a percentage of the forced vital capacity (FEV1% pred) on pulmonary function testing.

Methods

The data of 359 patients with chronic obstructive pulmonary disease (COPD) with available FEV1% pred and computed tomography (CT) images were retrospectively reviewed. FACT-Digital lung TM software (DeXin, Xi’an, China) was used to perform fully automated three-dimensional CT quantitative measurements of the bronchi. Generation 5 to 7 bronchi were measured, and the parameters analyzed were the lumen diameter (LD), wall thickness (WT), lumen area (LA), and WA% [WA / (WA + LA) × 100%].

Results

In the smoking, smoking cessation, and nonsmoking groups, women had a significantly larger WA% and smaller LD, WT, and LA than men. The FEV1% pred was significantly lower in women than men in the smoking and smoking cessation groups. The FEV1% pred was significantly higher in women than men in the nonsmoking group.

Conclusion

Sex-related differences may partially explain why smoking women experience more severe pulmonary function impairment than men among patients with COPD.
Autonomous path following by fuzzy adaptive curvature-based point selection algorithm for four-wheel-steering car-like mobile robot
Authors: Ghaffari S , Homaeinezhad MR
Published: July 2017

Autonomous path following in mobile robots with nonholonomic constraints can be divided into two problems: first, selecting the tracking point, and then designing an appropriate controller to follow the selected point. When selecting tracking point, considering the kinematics of the robot as well as characteristics of the desired path is of considerable importance. For these purposes, a curvature-based point selection algorithm is first proposed for the car-like mobile robot with independent steering mechanisms. Each instant, the proposed algorithm finds a point which enables the robot to be tangent to the path at that specific point. Afterwards, in order to take into consideration characteristics of the path, a fuzzy adaptive curvature-based point selection algorithm is proposed. In this algorithm, in addition to the kinematic constraints, path characteristics are also considered in selecting the tracking point. This gives the robot the ability to show better performance when the path slope changes suddenly, resulting in less overshoot/undershoot around the desired path. The fuzzy adaptive curvature-based point selection algorithm is combined with a controller based on the Takagi–Sugeno fuzzy logic, such that the fuzzy adaptive curvature-based point selection algorithm selects the tracking point, while the Takagi–Sugeno fuzzy logic controller makes the robot follow the selected point. Finally, the fuzzy adaptive curvature-based point selection–Takagi–Sugeno fuzzy logic tracker is implemented on the robot, and the results are compared with a similar path-following algorithm. Obtained results show that for tracking a piecewise linear path, the steering activity and the following root mean square error decrease from 170.74° and 0.37 m for the conventional fuzzy controller to 63.37° and 0.09 m for the fuzzy adaptive curvature-based point selection–Takagi–Sugeno fuzzy logic controller, respectively.
Modeling rational, psychological, and social behavior toward diffusion of new technology using agent-based simulation: the case of the public utility jeepney (PUJ) fleet in Metro Manila
Authors: Ahanchian Mohammad , Biona Jose Bienvenido Manuel
Published: July 2017

In most developing countries, over-aged vehicles play a significant role in energy demand and air pollution, which make the transportation sector a suitable choice for investigating opportunities to mitigate climate change. Apparently, people heterogeneity, social influence, and network configuration affect diffusion of innovation. This study presents an agent-based model (ABM) to simulate the rational decision-making, psychological behavior, and social interaction of people to explore their reaction to policy scenarios toward adopting technological changes over time. The aim of model is to assist policymakers for energy and environmental policy design based on consumers’ behavior. The jeepney owners in the old public utility jeepney (PUJ) fleet in Metro Manila are chosen as case study to prove the applicability of the model. The results show that rational, psychological, and social interaction of owners could not lead to diffusion of technology without intervention of policy instruments. However, by implementing incentive-based policies, the entire jeepney fleet could be renovated before the end of simulation horizon and the government could launch a 5-year plan to combat pollution of the fleet. The model could be applied to evaluate and prioritize strategies for reducing the future energy requirements and emissions in other fleets and regions.
TLISMNI/Adams algorithm for the solution of the differential/algebraic equations of constrained dynamical systems
Authors: Shabana Ahmed A , Zhang Dayu , Wang Gengxiang
Published: July 2017

This paper examines the performance of the 3rd and 4th order implicit Adams methods in the framework of the two-loop implicit sparse matrix numerical integration method in solving the differential/algebraic equations of heavily constrained dynamical systems. The variable-step size two-loop implicit sparse matrix numerical integration/Adams method proposed in this investigation avoids numerical force differentiation, ensures satisfying the nonlinear algebraic constraint equations at the position, velocity, and acceleration levels, and allows using sparse matrix techniques for efficiently solving the dynamical equations. The iterative outer loop of the two-loop implicit sparse matrix numerical integration/Adams method is aimed at achieving the convergence of the implicit integration formulae used to solve the independent differential equations of motion, while the inner loop is used to ensure the convergence of the iterative procedure used to satisfy the algebraic constraint equations. To solve the independent differential equations, two different implicit Adams integration formulae are examined in this investigation; a 3rd order implicit Adams-Moulton formula with a 2nd order explicit predictor Adams Bashforth formula, and a 4th order implicit Adams-Moulton formula with a 3rd order explicit predictor Adams Bashforth formula. A standard Newton–Raphson algorithm is used to satisfy the nonlinear algebraic constraint equations at the position level. The constraint equations at the velocity and acceleration levels are linear, and therefore, there is no need for an iterative procedure to solve for the dependent velocities and accelerations. The algorithm used for the error check and step-size change is described. The performance of the two-loop implicit sparse matrix numerical integration/Adams algorithm developed in this investigation is evaluated by comparison with the explicit predictor-corrector Adams method which has a variable-order and variable-step size. Simple and heavily constrained dynamical systems are used to evaluate the accuracy, robustness, damping characteristics, and effect of the outer-loop iterations of the proposed implicit schemes. The results obtained in this investigation show that the two-loop implicit sparse matrix numerical integration methods proposed in this study can be more efficient for stiff systems because of their ability to damp out high-frequency oscillations. Explicit integration methods, on the other hand, can be more efficient in the case of non-stiff systems.
SwarmSim: a framework for modeling swarming unmanned aerial vehicles using Hardware-in-the-Loop
Authors: Worth Derek B , Woolley Brian G , Hodson Douglas D
Published: July 2017

Unmanned Aerial Vehicle (UAV) swarm applications, algorithms, and control strategies have experienced steady growth and development over the past 15 years. Yet, to date, most swarm development efforts have gone untested and unimplemented. The major inhibitors to successful swarm implementation seem to include the cost of aircraft systems, government imposed airspace restrictions, and the lack of adequate modeling and simulation tools. This paper examines how the open-source OpenEaagles simulation framework was leveraged to bridge this gap to create Hardware-in-the-Loop (HIL) simulations. Leveraging OpenEaagles through software extension to create HIL simulations provides developers with a functional capability with which to develop and test the behaviors of scalable and modular swarms of autonomous UAVs. Using HIL-based simulations in this capacity provides assurance that defined behaviors will propagate to live flight tests in the real world. The demonstrations in the work show how the framework enhances and simplifies swarm development through encapsulation, possesses high modularity, provides realistic aircraft modeling, and is capable of simultaneously accommodating multiple hardware-piloted and purely simulated swarming UAVs during simulation.
Cobra neurotoxin produces central analgesic and hyperalgesic actions via adenosine A1 and A2A receptors
Authors: Zhao Chuang , Zhao Jun , Yang Qian , Ye Yong
Published: July 2017

Cobra neurotoxin, a short-chain peptide isolated from snake venom of Naja naja atra, showed both a central analgesic effect and a hyperalgesic effect in mice tests. In order to explore mechanisms, a hypothesis is put forward that cobra neurotoxin takes effect through adenosine receptor pathway. The central effects of cobra neurotoxin were evaluated using the hot plate test (a model of acute pain) and the spinal cord injury (a model of central pain) in mice and using A1 receptor antagonist (DPCPX) and A2A receptor antagonist (ZM241385); behaviors were scored and signal molecules such as reactive oxygen species and adenosine triphosphate levels and mitogen-activated protein kinases/extracellular signal-regulated protein kinase expression were measured. Low dose of cobra neurotoxin (25 µg/kg) had analgesic effects which were inhibited by DPCPX, while high dose of cobra neurotoxin (100 µg/kg) had hyperalgesic effects which were blocked by ZM241385. Cobra neurotoxin reduced reactive oxygen species and increased adenosine triphosphate in brain tissues, and extracellular signal-regulated protein kinase expression was markedly inhibited by cobra neurotoxin. Cobra neurotoxin may take effect through mitogen-activated protein kinases/extracellular signal-regulated protein kinase pathway inhibition by activating adenosine A1Rs and cause changes of reactive oxygen species and adenosine triphosphate through feedback mechanisms. Overdose cobra neurotoxin further activates the adenosine A2ARs to generate pain sensitization. This research proposes a new central analgesic mechanism of cobra neurotoxin and discloses dual regulation of pain.
What is the Natural History of Patellar Dislocation in Skeletally Immature Patients?
Authors: Sanders Thomas L. , Pareek Ayoosh , Hewett Timothy E. , Stuart Michael J. , Dahm Diane L. , Krych Aaron John
Published: July 2017

Objectives:

Patellar dislocation can occur in isolation or be associated with chronicinstability. The goals of this study are to describe the rate and factors associated with additional patellar instability events (ipsilateral recurrence and contralateral dislocation), as well as the incidence of patellofemoral arthritis among skeletally immature patients following patellar dislocation.

Methods:

The study included a population-based cohort of 232 skeletally immature patients who experienced a first-time lateral patellar dislocation between 1990 and 2010. A chart review was performed to collect information related to the initial injury, treatment, and outcomes. Subjects were followed for a mean of 12.1 years to determine the rate of subsequent patellar dislocation (ipsilateral recurrence or contralateral dislocation) as well as clinically significant patellofemoral arthritis.

Results:

104 patients had ipsilateral recurrent patellar dislocation. The cumulative incidence of recurrent dislocation was 11% at 1 year, 21.1% at 2 years, 37.0% at 5 years, 45.1% at 10 years, 54.0 % at 15 years, and 54.0% at 20 years. Patella alta (HR: 10.6, 95% CI: 3.6, 36.1), increased TT-TG distance (HR 18.7, 95% CI: 1.7, 228.2), and trochlear dysplasia (HR 23.7, 95% CI: 1.0, 105.2) were associated with recurrence. Similarly, 18 patients (7.8%) had contralateral patellar dislocation. The cumulative incidence of patellofemoral arthritis was 0% at 2 years, 1.0% at 5 years,2.0% at 10 years, 10.1% at 15 years, 17%% at 20 years, and 39.0% at 25 years. Osteochondral injury was associated with arthritis (HR 25.7, 95% CI: 6.2, 143.8).

Conclusion:

Skeletally immature patients have a high rate of recurrent patellarinstability that is associated with structural abnormalities such as patella alta and trochlear dysplasia. In contrast, the rate of subsequent contralateral dislocation is low. Osteochondral injury is associated with arthritis after patellar dislocation, but the overall incidence of symptomatic arthritis with advanced radiographic changes in pediatric patients is low at 12-year follow-up.
The Influence of a Single Preoperative Ketorolac Dose on Postoperative Opiate Consumption for Ambulatory Knee Arthroscopy: A Double Blinded Placebo Controlled Study
Authors: Slone Harris , Epperson Thomas , Furse Cory , Wolf Bethany , Wilson Sylvia
Published: July 2017

Objectives:

Ketorolac is a non-steroidal anti-inflammatory known to decrease postoperative opiate requirements. While many studies have examined serial ketorolac doses over 48 hours, the optimal ketorolac dose for analgesia following ambulatory surgery is not established. We examined postoperative opiate consumption in morphine equivalents (ME) for patients receiving a randomized ketorolac dose for knee arthroscopy.

Methods:

Patients undergoing elective, outpatient knee arthroscopy were randomized a dose of ketorolac (0 mg, 7.5 mg, 15 mg, 30 mg) in a double blinded placebo controlled fashion. Postoperative opiate consumption was the primary outcome. Secondary endpoints were patient satisfaction score, Visual Analog Pain Scores (VAS) pre- and postoperative, side effects and total PACU time. Logistic regression was used to compare the results among the different ketorolac groups.

Results:

A total of 112 patients were enrolled with comparable patient and procedural characteristics in each group. Mean postoperative opiate consumption in ME was 6.36 mg across all groups. The median VAS at PACU arrival was 3.0 and at discharge was 1.6. Median patient satisfaction across all treatment groups was 9.8 out of 10. In univariate models, increased postoperative morphine consumption was associated with decreased ketorolac dose ( P=0.037) and female gender ( P=0.021). In a multivariable model, patients that received 7.5 fewer mg of ketorolac consumed on average 0.6 mg more ME postoperatively controlling for other factors ( P=0.034). Females consumed an average of 2.3 mg more opiates relative to males after controlling for ketorolac dose ( P=0.006). Ketorolac dose was not associated with the occurrence of side effects ( P=0.722). Side effects were associated with female gender ( P=0.023) and increased BMI ( P=0.022). Consumption of each additional 1 mg of postoperative ME had a 13% increase in the odds of having at least one side effect controlling for other factors ( P=0.026, 95% CI: 1.02-1.26).

Conclusion:

Decreased ketorolac dose is associated with increased opiate consumption controlling other factors. Increased opiate consumption may result in increased side effects, although this did not impact patient satisfaction.
Mid-term Outcomes of the Subchondroplasty Procedure for Patients with Osteoarthritis and Bone Marrow Edema
Authors: Byrd Jennifer Marie , Akhavan Sam , Frank Darren A.
Published: July 2017

Objectives:

Bone marrow edema (BME) is a negative prognostic factor for patients with knee osteoarthritis (KOA). BME is strongly associated with pain, decreased function, structural deterioration and rapid progression to total knee arthroplasty (TKA). Subchondroplasty (SCP) (Knee Creations, Zimmer, Warsaw, IN) directly addresses BME in the setting of KOA by injecting calcium phosphate cement into the area of BME. The objective of this research was to show clinical results of the SCP procedure.

Methods:

A retrospective chart review with follow-up questionnaire was conducted on SCP patients in short-term and midterm (>2 years). All patients failed conservative measures and were candidates for TKA. The questionnaire addressed symptoms before and after SCP, further interventions, the perception of and willingness to undergo SCP again.

Results:

133 of 143 subchondroplasty patients responded. The average patient was 57 years old (38-84 years) and 47% male. The average follow-up for short-term patients was 14.6 (4-22) months and for mid-term patients was 32.1 (24-43) months. Pain score decreased from 8.3 pre-op to 3.4 post-op in both groups. 35% in the short-term group required injections, increasing to 41% in the mid-term. The short-term group demonstrated satisfaction of 8.3 out of 10, with 82% willing to undergo SCP again and 89% recommending SCP. In the mid-term group, satisfaction increased to 8.5 with 95% willing to undergo SCP again and 96% recommending the procedure. In all, 32 patients (25%) progressed to TKA (Figure 1) at an average of 17.8 months, with 22 (69%) of these occurring before 2 years.

Conclusion:

SCP is an effective and well received treatment for patients with KOA and BME. In patients who failed conservative measures and were considering TKA, excellent results are seen at 2.5 years follow-up with only 25% of patients requiring TKA. Of all patients not requiring TKA, 93% would undergo SCP again and 98% would recommend it. [Table: see text]
Does Treatment of the Tibia Matter in Bipolar Chondral Defects of the Knee? Clinical Outcomes with Greater Than Two Years Follow-Up
Authors: Weber Alexander E. , Hannon Charles Patrick , Meyer Maximilian A. , Poland Sarah Glen , Yanke Adam Blair , Cole Brian J.
Published: July 2017

Objectives:

The purpose of this study was twofold: 1) to investigate the optimal treatment of bipolar tibiofemoral cartilage lesions by comparing femoral osteochondral allograft (OCA) with tibial debridement to bipolar lesions treated with femoral OCA and tibial microfracture and 2) to compare the outcomes of bipolar lesions with isolated femoral defects treated with OCA.

Methods:

A series of 36 patients undergoing femoral OCA for bipolar lesions was identified. Group 1 contained 20 patients with tibial lesions treated with debridement, Group 2 contained 16 patients with tibial lesions treated with microfracture, and Group 3 (control group) contained 20 patients with isolated femoral lesions treated with OCA. Group 3 was matched by gender, BMI, laterality, and OCA size to Groups 1 and 2. Patient-specific, defect-specific data was collected. Patient reported outcomes (PROs) including International Knee Documentation Committee (IKDC) scores, Short Form 12 (SF-12) scores, Knee Injury and Osteoarthritis Outcome Scores (KOOS), and Lysholm scores, were recorded. All patients had greater than two-year follow-up.

Results:

There were no significant differences between the three groups in terms of gender, body mass index (BMI), number of previous surgeries, femoral or tibial defect size, and OCA size. Preoperative to postoperative patient reported clinical outcomes (PROs) demonstrated statistical and clinically meaningful improvement in all 3 groups (p < 0.05), without differences between groups (Figure 1). Patient-specific and defect-specific factors did not significantly correlate with PROs. The graft survivorship for Group 1 was 85% at 4.5 years, 100% for Group 2 at 2.5 years, and 95% for Group 3 at 3.8 years.

Conclusion:

Regardless of tibial treatment, debridement or microfracture, patients with bipolar cartilage lesions treated with femoral OCA have significant and clinically meaningful improvements in PROs, which are comparable to isolated femoral defects treated with OCA. In addition, bipolar lesions treated with OCA had excellent graft survivorship at greater than two-years follow-up.