bluuebunny/crossref_metadata_2025_split huggingface dataset:
Densely Ionizing Radiation Acts via the Microenvironment to Promote Aggressive Trp53-Null Mammary Carcinomas
Authors: Illa-Bochaca Irineu , Ouyang Haoxu , Tang Jonathan , Sebastiano Christopher , Mao Jian-Hua , Costes Sylvain V. , Demaria Sandra , Barcellos-Hoff Mary Helen 
Published: October 2014

Abstract
Densely ionizing radiation, which is present in the space radiation environment and used in radiation oncology, has potentially greater carcinogenic effect compared with sparsely ionizing radiation that is prevalent on earth. Here, we used a radiation chimera in which mice were exposed to densely ionizing 350 MeV/amu Si-particles, γ-radiation, or sham-irradiated and transplanted 3 days later with syngeneic Trp53-null mammary fragments. Trp53-null tumors arising in mice irradiated with Si-particles had a shorter median time to appearance and grew faster once detected compared with those in sham-irradiated or γ-irradiated mice. Tumors were further classified by markers keratin 8/18 (K18, KRT18), keratin 14 (K14, KRT14) and estrogen receptor (ER, ESR1), and expression profiling. Most tumors arising in sham-irradiated hosts were comprised of both K18- and K14-positive cells (K14/18) while those tumors arising in irradiated hosts were mostly K18. Keratin staining was significantly associated with ER status: K14/18 tumors were predominantly ER-positive, whereas K18 tumors were predominantly ER-negative. Genes differentially expressed in K18 tumors compared with K14/18 tumor were associated with ERBB2 and KRAS, metastasis, and loss of E-cadherin. Consistent with this, K18 tumors tended to grow faster and be more metastatic than K14/18 tumors, however, K18 tumors in particle-irradiated mice grew significantly larger and were more metastatic compared with sham-irradiated mice. An expression profile that distinguished K18 tumors arising in particle-irradiated mice compared with sham-irradiated mice was enriched in mammary stem cell, stroma, and Notch signaling genes. These data suggest that carcinogenic effects of densely ionizing radiation are mediated by the microenvironment, which elicits more aggressive tumors compared with similar tumors arising in sham-irradiated hosts. Cancer Res; 74(23); 7137–48. ©2014 AACR.
The Paracrine Hormone for the GUCY2C Tumor Suppressor, Guanylin, Is Universally Lost in Colorectal Cancer
Authors: Wilson Chantell , Lin Jieru E. , Li Peng , Snook Adam E. , Gong Jianping , Sato Takahiro , Liu Chengbao , Girondo Melanie A. , Rui Hallgeir , Hyslop Terry , Waldman Scott A. 
Published: October 2014

Abstract
Background: Although colorectal cancer is a disease characterized by sequential accumulation of mutations in epithelial cells, mechanisms leading to genomic vulnerability contributing to tumor initiation remain undefined. GUCY2C has emerged as an intestine-specific tumor suppressor controlling epithelial homeostasis through circuits canonically disrupted in cancer. Surprisingly, the GUCY2C tumor suppressor is universally overexpressed by human colorectal cancer cells. This apparent paradox likely reflects silencing of GUCY2C through loss of its paracrine hormone guanylin. Here, we quantified expression of guanylin mRNA and protein in tumors and normal epithelia from patients with colorectal cancer.
Methods: Guanylin mRNA was quantified in tumors and normal adjacent epithelia from 281 patients by the reverse transcriptase-polymerase chain reaction. Separately, the guanylin protein was quantified by immunohistochemistry in 54 colorectal tumors and 30 specimens of normal intestinal epithelium.
Results: Guanylin mRNA in colorectum varied more than a 100-fold across the population. Guanylin mRNA was reduced 100- to 1,000-fold in &gt;85% of tumors compared with matched normal adjacent mucosa (P &lt; 0.001). Loss of guanylin mRNA was greatest in tumors from patients &lt;50 years old (P &lt; 0.005) and with the highest expression in normal adjacent mucosa (Spearman correlation coefficient = 0.61; P &lt; 0.001). In a separate validation cohort, guanylin protein was detected in all 30 normal colorectal mucosa specimens, but in none of 54 colorectal tumors.
Conclusions: Colorectal cancer may initiate as a disease of paracrine hormone insufficiency through loss of guanylin expression, silencing the GUCY2C tumor suppressor and disrupting homeostatic mechanisms regulating colorectal epithelia cells.
Impact: Intestinal tumorigenesis may be prevented by oral GUCY2C hormone replacement therapy. Cancer Epidemiol Biomarkers Prev; 23(11); 2328–37. ©2014 AACR.
Serum Lipid Profile and Risk of Prostate Cancer Recurrence: Results from the SEARCH Database
Authors: Allott Emma H. , Howard Lauren E. , Cooperberg Matthew R. , Kane Christopher J. , Aronson William J. , Terris Martha K. , Amling Christopher L. , Freedland Stephen J. 
Published: October 2014

Abstract
Background: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance.
Methods: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines.
Results: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01–1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01–1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41–0.91), respectively.
Conclusions: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively.
Impact: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence. Cancer Epidemiol Biomarkers Prev; 23(11); 2349–56. ©2014 AACR.
DAPK3 Suppresses Acini Morphogenesis and Is Required for Mouse Development
Authors: Kocher Brandon A. , White Lynn S. , Piwnica-Worms David 
Published: October 2014

Abstract
Death-associated protein kinase (DAPK3) is a serine/threonine kinase involved in various signaling pathways important to tissue homeostasis and mammalian biology. Considered to be a putative tumor suppressor, the molecular mechanism by which DAPK3 exerts its suppressive function is not fully understood and the field lacks an appropriate mouse model. To address these gaps, an in vitro three-dimensional tumorigenesis model was used and a constitutive DAPK3-knockout mouse was generated. In the 3D morphogenesis model, loss of DAPK3 through lentiviral-mediated knockdown enlarged acinar size by accelerated acini proliferation and apoptosis while maintaining acini polarity. Depletion of DAPK3 enhanced growth factor–dependent mTOR activation and, furthermore, enlarged DAPK3 acini structures were uniquely sensitive to low doses of rapamycin. Simultaneous knockdown of RAPTOR, a key mTORC1 component, reversed the augmented acinar size in DAPK3-depleted structures indicating an epistatic interaction. Using a validated gene trap strategy to generate a constitutive DAPK3-knockout mouse, it was demonstrated that DAPK3 is vital for early mouse development. The Dapk3 promoter exhibits spatiotemporal activity in developing mice and is actively expressed in normal breast epithelia of adult mice. Importantly, reduction of DAPK3 expression correlates with the development of ductal carcinoma in situ (DCIS) and more aggressive breast cancer as observed in the Oncomine database of clinical breast cancer specimens.
Implications: Novel cellular and mouse modeling studies of DAPK3 shed light on its tumor-suppressive mechanisms and provide direct evidence that DAPK3 has relevance in early development. Mol Cancer Res; 13(2); 358–67. ©2014 AACR.
Thrombosis
Authors: Raskob G.E. , Angchaisuksiri P. , Blanco A.N. , Buller H. , Gallus A. , Hunt B.J. , Hylek E.M. , Kakkar A. , Konstantinides S.V. , McCumber M. , Ozaki Y. , Wendelboe A. , Weitz J.I. 
Published: October 2014

Background—
Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability.

Objective—
To review the literature on the global burden of disease caused by VTE.

Approach and Results—
We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events.

Conclusions—
VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.
A Horizon-Tracking Method for Shipboard Video Stabilization and Rectification
Authors: Schwendeman Michael , Thomson Jim 
Published: October 2014

AbstractAn algorithm is presented for the stabilization and rectification of digital video from floating platforms. The method relies on a horizon-tracking technique that was tested under a variety of lighting and sea-state conditions for 48 h of video data over 12 days during a research cruise in the North Pacific Ocean. In this dataset, the horizon was correctly labeled in 92% of the frames in which it was present. The idealized camera model assumes pure pitch-and-roll motion, a flat sea surface, and an unobstructed horizon line. Pitch and roll are defined along the camera look direction rather than in traditional ship coordinates, such that the method can be used for any heading relative to the ship. The uncertainty in pitch and roll is estimated from the uncertainties of the horizon-finding method. These errors are found to be of the order 0.6° in roll and 0.3° in pitch. Errors in rectification are shown to be dominated by the uncertainty in camera height, which may change with the heave motion of a floating platform. The propagation of these errors is demonstrated for the breaking-wave distribution Λ(c). A toolbox for implementation of this method in MATLAB is shared via the MATLAB File Exchange.
Navigating the Complexities of Qualitative Comparative Analysis
Authors: Thiem Alrik 
Published: October 2014

Background: In recent years, the method of Qualitative Comparative Analysis (QCA) has been enjoying increasing levels of popularity in evaluation and directly neighboring fields. Its holistic approach to causal data analysis resonates with researchers whose theories posit complex conjunctions of conditions and events. However, due to QCA’s relative immaturity, some of its technicalities and objectives have not yet been well understood. Objectives: In this article, I seek to raise awareness of six pitfalls of employing QCA with regard to the following three central aspects: case numbers, necessity relations, and model ambiguities. Most importantly, I argue that case numbers are irrelevant to the methodological choice of QCA or any of its variants, that necessity is not as simple a concept as it has been suggested by many methodologists, and that doubt must be cast on the determinacy of virtually all results presented in past QCA research. Method: By means of empirical examples from published articles, I explain the background of these pitfalls and introduce appropriate procedures, partly with reference to current software, that help avoid them. Conclusion: QCA carries great potential for scholars in evaluation and directly neighboring areas interested in the analysis of complex dependencies in configurational data. If users beware of the pitfalls introduced in this article, and if they avoid mechanistic adherence to doubtful “standards of good practice” at this stage of development, then research with QCA will gain in quality, as a result of which a more solid foundation for cumulative knowledge generation and well-informed policy decisions will also be created.
Museums, Zoos, and Gardens
Authors: Weinstein Meryle , Whitesell Emilyn Ruble , Schwartz Amy Ellen 
Published: October 2014

Background: Informal science education institutions (ISEIs) are critical partners in public science education, as they support the science efforts of school systems by providing authentic opportunities for scientific inquiry. This study reports findings from an evaluation of urban advantage (UA), a collaboration between the New York City Department of Education and eight ISEIs designed to improve science education in New York City (NYC) middle schools. Now in its 10th year, the program harnesses the resources and expertise of NYC’s ISEIs to (a) enhance the science content knowledge of middle school science teachers, (b) develop teachers’ skills at using inquiry-based approaches in their classrooms, and (c) improve the science achievement of middle school students. Objectives: We examine whether the UA program has led to increased student achievement on the eighth-grade New York State standardized science exam for students in participating schools; in supplemental analyses, we examine the effects on longer term (ninth-grade) outcomes. Research Design: We use a difference-in-differences framework with school fixed effects to estimate the impact of attending a UA school in eighth grade on science achievement. Measures: Our key outcome is performance on New York State’s eighth-grade intermediate-level science assessment; longer term outcomes include enrollment at specialized science, technology, engineering, and math high schools as well as taking and passing the high school (Regents) science exams. Results: We find that attending a UA school increases student performance on the eighth-grade science exam by approximately 0.05 SD, and there is some evidence of small effects on Regents taking and passing rates.
Biomechanics of the Rhombic Transposition Flap
Authors: Topp Shelby G. , Lovald Scott , Khraishi Tariq , Gaball Curtis W. 
Published: October 2014

ObjectiveTo develop a computational model of cutaneous wound closures comparing variations of the rhombic transposition flap.Study DesignA nonlinear hyperelastic finite element model of human skin was developed and used to assess flap biomechanics in simulated rhombic flap wound closures as flap geometric parameters were varied.SettingIn silico.MethodsThe simulation incorporated variables of transposition angle, flap width, and tissue undermining. A 2‐dimensional second‐order Yeoh hyperelastic model was fit to published experimental skin data. Resultant stress and strain fields as well as local surface changes were evaluated.ResultsFor the rhombus defect, closure stress and strain were minimized for the transposition flap with a distal flap angle of 30° by recruiting skin from opposing sides of the defect. Alteration of defect dimensions showed that peak stress and principal strain were minimized with a square defect. Likelihood of a standing cutaneous deformity was driven by the magnitude of angle closure at the flap base. Manipulation of the transposition angle reoriented the primary skin strain vector. Asymmetric undermining decoupled wound closure tension from strain, with direct effects on boundary deformation.ConclusionsThe model demonstrates that flap width determines the degree of secondary tissue movement and impact on surrounding tissues. Transposition angle determines the orientation of maximal strain. Local flap design requires consideration of multiple factors apart from idealized biomechanics, including adjacent “immobile” structures, scar location, local skin thickness, and orientation of relaxed skin tension lines. Finite element models can be used to analyze local flap closures to optimize outcomes.
The Effect of Early and Late Tracheotomy on Outcomes in Patients: A Systematic Review and Cumulative Meta‐analysis
Authors: Liu Xiao , Wang Hong‐Chao , Xing Ya‐Wei , He Yan‐Ling , Zhang Ze‐Feng , Wang Tao 
Published: October 2014

ObjectiveTo compare the effect of early tracheotomy (ET) and late tracheotomy (LT) on ventilator‐associated pneumonia (VAP) incidence and short‐term mortality in critically ill patients who received mechanical ventilation.Data SourcesWe searched databases of PubMed, Embase, and others for randomized controlled trials (RCTs) that compared ET (≤8 days after admission to the intensive care unit, initiation of translaryngeal intubation, or initiation of mechanical ventilation) with LT (≥6 days) in critically ill patients.Review MethodsThe overall odds ratio (OR) was estimated by traditional meta‐analysis. In addition, cumulative meta‐analysis was conducted by adding 1 study at a time in the order of year of publication.ResultsA total of 11 RCTs involving 1436 patients (708 in the ET group and 728 in the LT group) were included in this analysis. Early tracheotomy could significantly reduce the short‐term mortality (OR = 0.74; 95% confidence interval [CI] [0.58, 0.95]) but did not reduce the VAP incidence (OR = 0.70; 95% CI [0.47, 1.04]). The cumulative meta‐analysis showed that evidence of the benefit of ET on VAP incidence was unstable over time. In contrast, the difference in short‐term mortality was stable from the first appearance during the cumulative meta‐analysis.ConclusionEarly tracheotomy could improve short‐term mortality but did not alter VAP incidence. Many factors may be responsible for the unstable results during cumulative meta‐analysis, and further study is still needed to explore the optimal timing of tracheotomy.
The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results
Authors: Adams Aubrey Manack , Serrano Daniel , Buse Dawn C , Reed Michael L , Marske Valerie , Fanning Kristina M , Lipton Richard B 
Published: October 2014

Background Longitudinal migraine studies have rarely assessed headache frequency and disability variation over a year. Methods The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a cross-sectional and longitudinal Internet study designed to characterize the course of episodic migraine (EM) and chronic migraine (CM). Participants were recruited from a Web-panel using quota sampling in an attempt to obtain a sample demographically similar to the US population. Participants who passed the screener were assessed every three months with the Core (baseline, six, and 12 months) and Snapshot (months three and nine) modules, which assessed headache frequency, headache-related disability, treatments, and treatment satisfaction. The Core also assessed resource use, health-related quality of life, and other features. One-time cross-sectional modules measured family burden, barriers to medical care, and comorbidities/endophenotypes. Results Of 489,537 invitees, we obtained 58,418 (11.9%) usable returns including 16,789 individuals who met ICHD-3 beta migraine criteria (EM (<15 headache days/mo): n = 15,313 (91.2%); CM (≥15 headache days/mo): n = 1476 (8.8%)). At baseline, all qualified respondents ( n = 16,789) completed the Screener, Core, and Barriers to Care modules. Subsequent modules showed some attrition (Comorbidities/Endophenotypes, n = 12,810; Family Burden (Proband), n = 13,064; Family Burden (Partner), n = 4022; Family Burden (Child), n = 2140; Snapshot (three months), n = 9741; Core (six months), n = 7517; Snapshot (nine months), n = 6362; Core (12 months), n = 5915). A total of 3513 respondents (21.0%) completed all modules, and 3626 (EM: n = 3303 (21.6%); CM: n = 323 (21.9%)) completed all longitudinal assessments. Conclusions The CaMEO Study provides cross-sectional and longitudinal data that will contribute to our understanding of the course of migraine over one year and quantify variations in headache frequency, headache-related disability, comorbidities, treatments, and familial impact.
Increased toll-like receptor 9 expression is associated with the severity of paraquat-induced lung injury in mice
Authors: Qian J , Liu L , Chen L , Lu X , Zhu C 
Published: October 2014

Background: Toll-like receptor 9 (TLR9), an important component of the innate immune system, contributes to the pathogenesis of lung injury. However, its role in paraquat (PQ)-induced lung injury has not been studied. Method: Mice were divided into PQ group ( n = 24) and control group ( n = 12). Mice in both groups were killed on either day 7 or day 28 after PQ (40 mg/kg intraperitoneally) or saline administration. TLR9 expression was evaluated through real-time polymerase chain reaction and immunohistochemistry. Concurrently, histopathological examinations of lung tissues were performed. On day 7, the lung weight to body weight ratios (LW/BW), total protein content, and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were measured. On day 28, fibrogenic cytokine expressions in lung tissues were measured. The correlations between TLR9 messenger RNA (mRNA) expression and different indicators of lung injury were then evaluated. Results: TLR9 expression was significantly increased over time in lung tissues after PQ poisoning. On day 7, TLR9 expression increased in parallel with LW/BW ratio ( r = 0.403, p < 0.05), BALF protein content ( r = 0.706, p<0.01), and BALF inflammatory cytokine levels (interleukin 6 (IL-6): r = 0.619, IL-1β: r = 0.930, tumor necrosis factor α: r = 0.589, all p < 0.05). On day 28, elevated TLR9 expression was closely correlated with Ashcroft score ( r = 0.726, p < 0.01), mRNA expressions of α-smooth muscle actin, type I collagen and type III collagen ( r = 0.926, 0.957, and 0.924, respectively; all p < 0.01). Conclusions: The TLR9 expression in lung tissue is markedly elevated during PQ-induced acute lung injury and pulmonary fibrosis and positively correlated with the severity of lung injury in mice.