bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY42-01: Chemical biology-based approach to understanding and overcoming resistance of cancers to therapies
Authors: Schreiber Stuart L. 
Published: August 2019

Abstract
The ability of cancer cells to resist apoptotic death induced by radiation, chemotherapy, targeted therapies and immunotherapy has been a primary impediment to achieving long-lasting clinical responses. Cancer resistance is often studied through the lens of genetics, and thus on a drug-by-drug basis. I will discuss an alternative approach - studying resistance through the lens of cellular plasticity. As part of the NCI’s Cancer Target Discovery & Development Network, we use the Cancer Therapeutics Response Portal (CTRP), which enables small molecule sensitivity-cancer cell feature relationships to be explored on a broad basis. One insight gained from this resource suggests that a similar form of plasticity appears recurrently in multiple cancer contexts, and in response to multiple modalities (chemotherapy; targeted therapy; immunotherapy) thus opening the possibility of a pan-cancer explanation of resistance. Here, cell plasticity provides access to an apoptosis-deficient state and thus resistance, and then subsequent cancer mutations, rather than being the basis of resistance, are needed to optimize the fitness of the resistant state for growth. We found that this myofibroblastic-like cell state has profound changes in lipid biology that result in a novel vulnerability to ferroptotic cell death and a dependency on the activity of GPX4, a potentially druggable lipid hydroperoxidas. We hope this research will provide a blueprint for the cure of cancers in the future.
Citation Format: Stuart L. Schreiber. Chemical biology-based approach to understanding and overcoming resistance of cancers to therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY42-01.
Abstract SY44-02: Aberrant polycomb repression in midline and hindbrain tumors
Authors: Lewis Peter W. 
Published: August 2019

Abstract
The discovery of high-frequency histone H3 missense mutations (‘oncohistones’) in pediatric gliomas was the first time that histone mutations were linked to any disease. Since the original discovery, monoallelic missense mutations in genes encoding histone H3 have been found in a variety of cancer types. Previous studies have led to mechanistic insights into how one class of oncohistones promotes tumorigenesis by demonstrating that lysine-to-methionine (K-to-M) substitutions transform histones from serving as substrates into specific and potent inhibitors of lysine methyltransferases.
Approximately 84% of diffuse intrinsic pontine glioma (DIPG) and 60% of high-grade non-brainstem pediatric midline gliomas contain a lysine 27-methionine (K27M) mutation. DIPG and other midline tumors have extremely low H3K27me3 levels caused by the action of the H3 K27M oncohistone. The H3 K27M protein binds to and inhibits the catalytic subunit (EZH2) of the Polycomb Repressive Complex 2 (PRC2), a conserved protein complex involved in gene silencing. Polycomb group (PcG) proteins are essential for development and are frequently misregulated in human cancers. Polycomb Repressive Complexes (PRC1, PRC2) function in a collaborative epigenetic cross-talk with H3K27me3 to initiate and maintain transcriptional silencing.
Posterior fossa type A (PFA) ependymomas also exhibit very low H3K27 methylation but lack the K27M oncohistone. Instead, PFA tumors express high levels of KIP75 (K27M-like inhibitor of PRC2, 75kDa, also termed CXORF67). We find that a highly conserved sequence within the C-terminus of KIP75 is necessary and sufficient to inhibit the catalytic activity of PRC2 in vitro and in vivo. Our biochemical experiments indicate that KIP75 directly interacts with the active site of the EZH2 subunit in a mechanism that is remarkably similar to the K27M oncohistone. Furthermore, expression of H3 K27M or KIP75 promote similar chromatin landscapes and gene expression profiles in cell culture. Our data indicate that PFA ependymoma and DIPG tumors are driven in part by the action of peptidyl PRC2 inhibitors that dysregulate gene silencing to promote tumorigenesis.
Citation Format: Peter W. Lewis. Aberrant polycomb repression in midline and hindbrain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY44-02.
Abstract SY45-02: Harnessing genetic interactions to advance whole-exome precision cancer treatment
Authors: Ruppin Eytan 
Published: August 2019

Abstract
Much of the current focus in cancer research is on studying cancer driver genes. In search for new and effective cancer drugs, this has been translated into searching for ‘actionable’ mutations in these genes, aiming at their therapeutic targeting. However, identifying novel genetic interactions occurring between cancer genes may open new drug treatment opportunities across the whole cancer genome. This talk will focus on studying the utility of two fundamental types of genetic interactions: The first are the well-known Synthetic Lethal interactions, describing the relationship between two genes whose combined inactivation is lethal to the cell. The second type are the much less studied Synthetic Rescues interactions, where a change in the activity of one gene is lethal to the cell but an alteration of its SR partner gene can rescue cell viability. I shall describe a new approach for the data-driven identification of these two types of genetic interactions by directly mining patients’ tumor data. Applying it to analyze the Cancer Genome Atlas (TCGA) data, we have identified the first pan-cancer genetic interaction networks shared across many types of cancer, which we then validated via existing and new experimental in vitro and in vivo screens. We find that: (a) Synthetic Lethal interactions offer an exciting venue for personalized selective anticancer treatments enabling the prediction of patients’ drug response and providing new selective drug target candidates, and (b) targeting Synthetic Rescue genes can mitigate resistance emerging to primary cancer therapy, including both targeted and immunotherapy. (c) Finally, I shall present recent unpublished results showing that we can quite accurately predict the context specificity of emerging synthetic-lethal based combination therapies, both in terms of the cancer types that are sensitive to them and re. the specific sensitivity of individual patients within a cancer type. Importantly, these results are obtained without the need for specific training on the datasets predicted and are derived directly from patients data, thus increasing the likelihood of their translational relevance.
Citation Format: Eytan Ruppin. Harnessing genetic interactions to advance whole-exome precision cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY45-02.
Defects in the Exocyst-Cilia Machinery Cause Bicuspid Aortic Valve Disease and Aortic Stenosis
Authors: Fulmer Diana , Toomer Katelynn , Guo Lilong , Moore Kelsey , Glover Janiece , Moore Reece , Stairley Rebecca , Lobo Glenn , Zuo Xiaofeng , Dang Yujing , Su Yanhui , Fogelgren Ben , Gerard Patrick , Chung Dongjun , Heydarpour Mahyar , Mukherjee Rupak , Body Simon C. , Norris Russell A. , Lipschutz Joshua H. 
Published: August 2019

Background:
Bicuspid aortic valve (BAV) disease is a congenital defect that affects 0.5% to 1.2% of the population and is associated with comorbidities including ascending aortic dilation and calcific aortic valve stenosis. To date, although a few causal genes have been identified, the genetic basis for the vast majority of BAV cases remains unknown, likely pointing to complex genetic heterogeneity underlying this phenotype. Identifying genetic pathways versus individual gene variants may provide an avenue for uncovering additional BAV causes and consequent comorbidities.

Methods:

We performed genome-wide association Discovery and Replication Studies using cohorts of 2131 patients with BAV and 2728 control patients, respectively, which identified primary cilia genes as associated with the BAV phenotype. Genome-wide association study hits were prioritized based on
P
value and validated through in vivo loss of function and rescue experiments, 3-dimensional immunohistochemistry, histology, and morphometric analyses during aortic valve morphogenesis and in aged animals in multiple species. Consequences of these genetic perturbations on cilia-dependent pathways were analyzed by Western and immunohistochemistry analyses, and assessment of aortic valve and cardiac function were determined by echocardiography.

Results:
Genome-wide association study hits revealed an association between BAV and genetic variation in human primary cilia. The most associated single-nucleotide polymorphisms were identified in or near genes that are important in regulating ciliogenesis through the exocyst, a shuttling complex that chaperones cilia cargo to the membrane. Genetic dismantling of the exocyst resulted in impaired ciliogenesis, disrupted ciliogenic signaling and a spectrum of cardiac defects in zebrafish, and aortic valve defects including BAV, valvular stenosis, and valvular calcification in murine models.

Conclusions:
These data support the exocyst as required for normal ciliogenesis during aortic valve morphogenesis and implicate disruption of ciliogenesis and its downstream pathways as contributory to BAV and associated comorbidities in humans.
Cross‐Sectional Study on the Management and Control of Hypertension Among Migrants in Primary Care: What Is the Impact of Segmented Health Insurance Schemes?
Authors: Li Haitao , Zhu Wu , Xia Hui , Wang Xuejun , Mao Chen 
Published: August 2019

Background
Information is scarce regarding the impact of fragmented health insurance schemes on the management and control of hypertension among migrants in primary care. This study aimed to investigate the relationship between insurance status and management and control of hypertension among migrants in primary care and to examine whether social capital could facilitate migrants’ participation in local health insurance schemes.

Methods and Results

A site‐based, cross‐sectional, face‐to‐face patient survey was administered in Shenzhen, China. Hypertensive primary care users who were migrants were selected using a systematic sampling design. The participants covered by local health insurance schemes were more likely than those without coverage to be managed by primary care facilities (82.6% versus 62.0%; odds ratio=2.63, 95%
CI
1.41‐4.89) and to take antihypertensive medications (87.9% versus 76.4%; odds ratio=2.38, 95%
CI
1.34‐4.24), and they had higher scores in first contact use (3.49 versus 3.23; β=0.17, 95%
CI
0.05‐0.29) and continuity of care (3.17 versus 3.02; β=0.11, 95%
CI
0.01‐0.21). The participants covered by local insurance schemes had higher scores in perceived generalized trust than their counterparts (4.23 versus 3.95; β=0.16, 95%
CI
0.09‐0.40). The hypertension control rate was also higher among the participants with local health insurance coverage (48.8% versus 42.2%; odds ratio=1.38, 95%
CI
1.02‐2.12).

Conclusions
In conclusion, local health insurance schemes are associated with optimal control of hypertension for migrants compared with social health insurance schemes. Our study implies that one form of social capital, namely perceived general trust, contributes to migrant hypertensive patients’ participation in local health insurance schemes.
Two Inversion Layers and Their Impacts on PM2.5 Concentration over the Yangtze River Delta, China
Authors: Xu Yiwen , Zhu Bin , Shi Shuangshuang , Huang Yong 
Published: August 2019

AbstractAn integrated winter field campaign was conducted to investigate the atmospheric boundary layer structure and PM2.5 concentration at three sites over the Yangtze River delta (YRD) in China: Shouxian (a rural area), a site in a northern suburb of Nanjing, and Dongshan (a residential area). Two temperature inversion layers and air pollution events occurred simultaneously from 30 to 31 December 2016, local time, over the YRD. It was found that the two inversion layers were related to the presence of a high pressure system, resulting in divergence in the upper boundary layer and radiative cooling near the ground at night. Dominated by agricultural and residential biomass burning, the surface emission sources from the Shouxian rural area were moderately strong. After the formation of the two inversions, the vertical distribution of PM2.5 concentration below the upper inversion layer was uniform as a result of thorough boundary layer mixing in the earlier hours. During nighttime at the Nanjing site, air pollutant plumes from nearby elevated point sources could not easily diffuse downward/upward between the two inversion layers, which led to a distinct peak in the PM2.5 concentration. At the Dongshan site, the emission sources were weak and the nighttime PM2.5 concentration above 100 m was high. The surface PM2.5 concentration gradually increased from early morning to noon, which was attributed to emissions related to the local residents. The results indicated that the vertical distribution of pollutants was affected by a combination of local emissions, vertical boundary layer structure, and horizontal and vertical transports.
Assessing Adaptive Mesh Refinement (AMR) in a Forced Shallow-Water Model with Moisture
Authors: Ferguson Jared O. , Jablonowski Christiane , Johansen Hans 
Published: August 2019

AbstractTwo forced shallow-water flow scenarios are explored in a 2D fourth-order finite-volume dynamical core with adaptive mesh refinement (AMR) to investigate AMR’s ability to track and resolve complex evolving features. Traditional shallow-water test cases are mainly characterized by large-scale smooth flows that do not effectively test the multiscale abilities of variable-resolution and AMR models to resolve sharp gradients and small-scale flow filaments. Therefore, adding forcing mechanisms to the shallow-water system to model key atmospheric processes adds complexity and creates small-scale phenomena. These can serve as foci for dynamic grid refinement while remaining simple enough to study the numerical design of a model’s dynamical core. The first shallow-water flow scenario represents a strengthening, tropical cyclone–like, vortex that is driven by a Betts–Miller-like convection scheme. The second shallow-water test is built upon a barotropically unstable jet with an added Kessler-like warm rain scheme that leads to precipitating frontal zones. The key feature of both tests is that there is significant sensitivity to the model grid while converging (structurally) at high resolution. Both test cases are investigated for a series of uniform resolutions and a variety of AMR tagging criteria. The AMR simulations demonstrate that grid refinement can resolve local features without requiring global high-resolution meshes. However, the results are sensitive to the refinement criteria. Criteria that trigger refinement early in a simulation reproduce the uniform-resolution reference solutions most reliably. In contrast, AMR criteria that delay refinement for several days require careful tuning of the AMR thresholds to improve results compared with uniform-resolution simulations.
Caudal Septal Division and Interposition Batten Graft: A Novel Technique to Correct Caudal Septal Deviation in Septoplasty
Authors: Kim Shin Ae , Jang Yong Ju 
Published: August 2019

Background: Correction of caudal septal deviation is a challenging task that may require multiple surgical approaches. Objective: To introduce a novel technique – caudal septal division and interposition batten graft – and evaluate its surgical outcomes in patients undergoing correction of caudal septal deviation. Method: The surgical procedure includes a division of the deviated caudal L-strut preserved after resection of the deviated quadrangular septal cartilage at the central portion. A batten graft made of septal cartilage or bone is interposed between the cut ends of the caudal L-strut, the upper part of which mobilized toward the more concave side of the nasal cavity, and then sutured. The medical records of 29 patients with caudal septal deviation who underwent septoplasty using caudal L-strut division and interposition batten graft technique between January 2016 and March 2018 were retrospectively reviewed. Patient satisfaction and symptom improvement were evaluated by using the Nasal Obstruction Symptoms Evaluation scores. Endoscopic assessment of deviation correction was performed and postoperative complications were analyzed. Results: Of the 29 patients, 19 (65.5%) answered the telephonic interview. Mean Nasal Obstruction Symptoms Evaluation scores were 62.1 preoperatively and 9.2 postoperatively, exhibiting significant improvement ( P < .001). Satisfaction was rated as much improved in 9 (32.0%) patients, improved in 16 (57.0%), unchanged in 2 (7%), and worse in 1 (4%). Records of endoscopic examinations showed that 26 (82.9%) patients had a straight septum, 4 (11.4%) had improved but persisting caudal deviation, and 2 (5.7%) had no available data. Four patients had postoperative complications: 2 had septal abscesses, 1 had wound dehiscence, and 1 had synechia. All of these complications were managed without persistent problems. Conclusions: Caudal septal division and interposition batten graft can serve as an alternative surgical approach with acceptable surgical outcomes for managing severely deviated caudal septum. Level of evidence: 4
Optimism and life satisfaction in persons with schizophrenia living in the community
Authors: Seo Myeong-Ah , Lim Young-Jin 
Published: August 2019

Background: This study aimed at examining the relationships between optimism and life satisfaction in persons with schizophrenia living in the community. Method: In total, 108 persons with schizophrenia who live in the community, ranging in age from 20 to 67 years, completed measures of optimism, perceived stress and life satisfaction. Results: Results showed that optimism significantly predicted life satisfaction even after controlling for gender, age, onset age, employment and perceived stress. Conclusion: Findings add further support to the growing body of evidence implicating that the intervention for enhancing life satisfaction in persons with schizophrenia dwelling in the community could focus on increasing optimism.
Preoperative intra-aortic balloon pump inserted in acute myocardial infarction patients without cardiogenic shock undergoing surgical coronary revascularization
Authors: Yang Feng , Wang Liangshan , Hou Dengbang , Wang Jinhong , Wang Xiaomeng , Cui Yongchao , Hao Xing , Xing Zhichen , Jiang Chunjing , Du Zhongtao , Yang Xiaofang , Miao Na , Jiang Yu , Xing Jialin , Hou Xiaotong 
Published: August 2019

Objectives: The benefit of preoperative intra-aortic balloon pump implantation in high-risk cardiac surgery patients is still debated. The role of preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting remains unknown. This study aimed to determine the efficacy and safety of the preoperative intra-aortic balloon pump insertion in those patients undergoing off-pump coronary artery bypass grafting. Methods: A total of 421 consecutive acute myocardial infarction patients without cardiogenic shock who underwent isolated off-pump coronary artery bypass grafting were enrolled in this retrospective observational propensity score–matched analysis study. Patients who received intra-aortic balloon pump before off-pump coronary artery bypass grafting (the intra-aortic balloon pump group, n = 157) were compared with those who had not (control group, n = 264). The 30-day postoperative survival, postoperative complications, and postoperative hospital length of stay were compared between the two groups. Results: A total of 99 pairs of patients were matched. The preoperative intra-aortic balloon pump did not show a 30-day postoperative survival benefit compared with the control group (hazard ratio, 0.9; 95% confidence interval, 0.2-4.2; p = 0.92). Patients with preoperative intra-aortic balloon pump were more likely to have shorter postoperative lengths of stay (8 (6-11) days vs. 10 (6-15) days, p = 0.02) and decreased total days in the hospital (median days: 18.2 vs. 21.8, p = 0.02) compared to patients without balloon pumps. Conclusion: Preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting improved convalescence as shown by significantly shorter postoperative lengths of hospital stay.
Novel Investigation of the Deep Band of the Lateral Plantar Aponeurosis and Its Relationship With the Lateral Plantar Nerve
Authors: Beck Cameron M. , Dickerson Austin R. , Kadado Kevin J. , Cohen Zachary A. , Blair Somer E. , Motley Travis A. , Holcomb Jenna C. , Fisher Cara L. 
Published: August 2019

Background: We describe a thick fascial band arising from the medial aspect of the lateral plantar aponeurosis diving deep into the forefoot crossing over a branch of the lateral plantar nerve. Because a review of current literature resulted in limited and outdated sources, we sought to first determine the frequency of this fascial band and the location where it crosses the lateral plantar nerve and, second, discuss the clinical applications these anatomical findings could have. Methods: 50 pairs of cadaveric feet (n = 100) were dissected to investigate for presence of the fascial band and its interaction with the lateral plantar nerve. Images were taken of each foot with the fascial band. ImageJ was used to take 2 measurements assessing the relationship of the tuberosity of the base of the fifth metatarsal to where the nerve crossed deep to the fascial band. Results: Overall, 38% of the feet possessed the fascial band. It was found unilaterally in 10 pairs and bilaterally in 14 pairs. On average, the point at which the lateral plantar nerve passed deep to the fascial band was 2.0 cm medial and 1.7 cm anterior to the tuberosity of the base of the fifth metatarsal. Conclusion: When present, the deep band of the lateral plantar aponeurosis (PA) was consistently found to be crossing the lateral plantar nerve. The discovery of the location where this most commonly occurs has not been previously reported and adds an interesting dimension that elevates an anatomical study to one that has clinical potential. Clinical Relevance: The established target zone gives a precise location for where the relationship between the deep band of the lateral PA and the lateral plantar nerve exists when evaluating the foot. The target zone provides a potential springboard for future investigations concerning said relationship clinically.