bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric validation of the Coronary Revascularisation Outcome Questionnaire (CROQv2) in the context of the NHS Coronary Revascularisation PROMs Pilot
Authors: Schroter Sara , Miles Rebecca , Green Stephen , Jackson Mark 
Published: March 2017

ObjectivesThe Coronary Revascularisation Outcome Questionnaire (CROQ) is a patient-reported outcome measure (PROM) for coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI). We tested the psychometric properties of a modified version (CROQv2) when administered in a National Health Service (NHS)/Department of Health (DH) funded pilot of PROMs for coronary revascularisation.DesignPsychometric validation study.Setting11 English hospitals in the UK taking part in the NHS/DH funded pilot of PROMs for coronary revascularisation.ParticipantsComprehensive analyses of acceptability, reliability, validity and responsiveness were conducted independently for each of the prerevascularisation (n=2685 and n=3711) and postrevascularisation (n=869 and n=837) versions of the CROQ-CABG and CROQ-PCI, respectively.ResultsAll versions met prespecified stringent criteria for (1) acceptability of items (missing data) and scales (missing data, floor and ceiling effects, skewness); (2) tests of scaling assumptions; (3) reliability: internal consistency (Cronbach's α, item-total correlations); (4) construct validity based on within-scale analyses (internal consistency, intercorrelations between scales, factor analysis and hypothesis testing); (5) construct validity based on comparisons with external measures (convergent and discriminant validity and hypothesis testing) and (6) responsiveness. Results were also confirmed when tests were repeated on subsamples of CABG (n=639) and PCI (n=615) patients who reported receiving help completing prerevascularisation questionnaires.ConclusionsThe availability of a psychometrically robust procedure-specific tool that could be used as part of a large-scale coronary revascularisation PROMs programme to capture the patients' perspective of coronary revascularisation will enable outcomes important to patients to be routinely collected alongside clinical outcomes. The CROQ is suitable for administration by postal survey or the prerevascularisation versions can be administered in the clinical setting as in the Coronary Revascularisation PROMs Pilot.
Annihilation rates of 3D2(2−−) and 3D3(3−−) heavy quarkonia
Authors: Wang Tianhong , Fu Hui-Feng , Jiang Yue , Li Qiang , Wang Guo-Li 
Published: March 2017

We calculate the annihilation decay rates of the [Formula: see text] and [Formula: see text] charmonia and bottomonia by using the instantaneous Bethe–Salpeter (BS) method. The wave functions of states with quantum numbers [Formula: see text] and [Formula: see text] are constructed. By solving the corresponding instantaneous BS equations, we obtain the mass spectra and wave functions of the quarkonia. The annihilation amplitude is written within Mandelstam formalism and the relativistic corrections are taken into account properly. This is important, especially for high excited states, since their relativistic corrections are large. The results for the [Formula: see text] channel are as follows: [Formula: see text] keV, [Formula: see text] keV, [Formula: see text] keV and [Formula: see text] keV.
Comment on the spherical quantum dot with interaction effects
Authors: Katriel Jacob 
Published: March 2017

A series of studies of the lowest [Formula: see text] state of a model of a two-electron quantum dot, that consists of a finite spherical well [see, for example, Sivakami et al., Int. J. Mod. Phys. B 24, 5561 (2010)], exhibited a range of interesting applications. However, the quantity of central interest, the expectation value of the interelectronic repulsion (that must be nonnegative) was calculated erroneously, yielding negative values. In the present note, this expectation value is evaluated with respect to the exact first-order perturbation theory wavefunction (the scheme considered in the papers cited above) as well as with respect to a minimal basis set Gaussian variational wavefunction. Reasonable agreement between the two schemes is confirmed, both yielding the expected positive values of the expectation value of the interelectronic repulsion, over the whole range of the relevant parameters.
Performance analysis on cascaded asymmetric photonic crystal Mach–Zehnder tunable filter
Authors: Chen Ying , Zhao Zhiyong , Liu Teng , He Lei , Di Yuanjian , Cui Xingning 
Published: March 2017

A cascaded asymmetric photonic crystal Mach–Zehnder filter structure is proposed to improve the quality factor (Q value) and the sensitivity of the tunable optical filter. The mathematical relationship between the output wavelength of M–Z filter and the voltage applied on the multilayer PZT is established. The simulation results show that the full width at half maximum can be decreased from 17 nm to 9 nm, in addition, the transmission peak wavelength varies by adjusting the applied voltage and the sensitivity can attain to 0.7 nm/V by using the multilayer PZT, which can achieve tunable filtering effectively.
An Adolescent and Early Adulthood Dietary Pattern Associated with Inflammation and the Incidence of Breast Cancer
Authors: Harris Holly R. , Willett Walter C. , Vaidya Rita L. , Michels Karin B. 
Published: March 2017

Abstract
Adolescence is a highly susceptible period for mammary carcinogenesis, but few prospective studies have examined the role of adolescent diet in breast cancer risk. Reduced rank regression has previously been used to identify a dietary pattern associated with markers of inflammation (C-reactive protein, IL6, and TNFα receptor 2). We investigated whether an adolescent and early adulthood inflammatory dietary pattern was associated with breast cancer among 45,204 women in the Nurses' Health Study II using reduced rank regression. Participants completed a food frequency questionnaire in 1998 about their high school diet (HS-FFQ) and a FFQ in 1991 when they were ages 27–44 years. Among women who completed the HS-FFQ, 1,477 cases of breast cancer were diagnosed during 22 years of follow-up. An adolescent and early adulthood dietary pattern characterized by inflammation was associated with an increased incidence of premenopausal but not postmenopausal breast cancer. Women in the fifth quintile of the inflammatory pattern score had multivariable adjusted HRs for premenopausal breast cancer of 1.35 for adolescent diet [95% confidence interval (95% CI), 1.06–1.73; Ptrend = 0.002] and 1.41 for early adulthood diet (95% CI, 1.11–1.78; Ptrend = 0.006) compared with women in the first quintile. The corresponding RRs for postmenopausal breast cancer were 0.84 (95% CI, 0.60–1.17) for adolescent and 0.76 (95% CI, 0.54–1.06) for adult intake. Overall, our findings support the notion that an adolescent and early adulthood diet characterized by high intake of sugar-sweetened and diet soft drinks, refined grains, red and processed meat, and margarine, and low intake of green leafy vegetables, cruciferous vegetables, and coffee may increase the incidence of premenopausal breast cancer. Cancer Res; 77(5); 1179–87. ©2017 AACR.
Abstract A12: Contribution of the transcription factor STAT2 in the promotion and progression of colorectal cancer
Authors: Kotredes Kevin P. , Gamero Ana M. 
Published: March 2017

Abstract
Accumulation of genetic lesions such as loss of, or mutations in the APC, KRAS, and TP53 genes play a pivotal role in the development and progression of colorectal cancer (CRC), the third most common cancer in the United States. Yet the effects deregulated signaling pathways, caused by these canonical alterations, may have on parallel signaling networks remain less clear. Signal Transducer and Activator of Transcription-2 (STAT2) is a critical molecule in the interferon transduction pathway, best known for its role in antiviral and antitumor immunity. However, we recently discovered that the transcription factor STAT2 functions as a promoter of colorectal carcinogenesis when tested in a model of colitis-associated CRC. In our recent study, we have reproduced this finding in which deletion of Stat2 in the ApcMin/+ mouse model of sporadic CRC also decreased the incidence and number of colon adenomas. We next investigated the role of STAT2 in the progression of CRC under the setting of p53 inactivation by employing isogenic colon carcinoma cells that differed in their p53 expression (p53+/+ vs. p53-/-). Our studies show that STAT2 knockdown weakened the oncogenic effects of p53 deficiency by drastically reducing migration and invasion whereas STAT2 knockdown had no effect in tumor cells with intact p53. In vivo, STAT2 depleted/p53-/- colon carcinoma cells, when transplanted in mice, formed smaller tumors when compared to tumor cells with intact STAT2 expression. Furthermore, we demonstrate expression of STAT2 dictates the expression of E-cadherin, a key epithelial-mesenchymal transition (EMT) marker, in the absence of p53. Additionally, evaluation of human CRC tissues revealed an increased STAT2 presence in the nucleus suggesting STAT2 is transcriptionally active in cancer; and genomic data mining of human CRC databases had led us to the identification of a putative STAT2 molecular signature upregulated in human CRC tumors. In conclusion, our study provides evidence that STAT2 has oncogenic properties thus positioning STAT2 as a major contributor to the pathophysiology of CRC.
Citation Format: Kevin P. Kotredes, Ana M. Gamero. Contribution of the transcription factor STAT2 in the promotion and progression of colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A12.
Abstract A16: Smad4 pathways modulate induction of the chemokine Ccl20 and repress inflammation-induced carcinogenesis in mouse colon
Authors: Means Anna L. , Freeman Tanner J. , Weaver Connie J. , Shi Chanjuan , Washington Mary K. , Wessinger Bronson C. , Brown Tasia , Flaherty David K. , Weller Kevin P. , Coffey Robert J. , Wilson Keith T. , Beauchamp Robert D. 
Published: March 2017

Abstract
Inflammation regulates many aspects of gut homeostasis but is also a key component of colon cancer progression. While TGFβ signaling is known to regulate inflammatory responses within immune cells, we have uncovered a novel regulatory pathway in which TGFβ and BMP signaling suppress responses to inflammatory stimuli within the colonic epithelium. Using mice with conditional deletion of Smad4 in intestinal epithelium, we found that CCL20 expression was increased with Smad4 loss. Similarly, in murine immortalized colonocytes and human colon cancer cell lines, blocking TGFβ and/or BMP receptors increased CCL20 expression. CCL20 is upregulated in response to inflammatory signals such as TNF and IL-1β. CCL20 is also upregulated in colon cancer but the mechanism is not understood. We found that pre-treatment of colonocytes or colon cancer cells with TGFβ1 and BMP2 completely suppressed TNF- or IL-1β-induced CCL20 expression at the level of gene transcription. By chromatin immunoprecipitation, we found that TGFβ1/BMP2 treatment impaired binding of NFκB and phospho-STAT3 to the CCL20 promoter. To understand the significance of this regulation in chronic inflammation, we subjected Smad4 deleted and control mice to three rounds of dextran sodium sulfate (DSS)-mediated damage to the distal colon. We found that loss of Smad4 in mouse colonic epithelium was sufficient to induce tumorigenesis following damage-induced inflammation. Following DSS-mediated damage, Smad4-null epithelium developed invasive colorectal adenocarcinoma within two months of DSS treatment while Smad4+ control mice never develop tumors following DSS exposure. The Smad4 null tumors were histologically similar to those of human colitis-associated colon cancers. Prior to tumor formation, we saw an increase in CD8+ cells in Smad4-deleted colons, suggesting that tumor progression involves bidirectional crosstalk between the epithelium and immune cells and that this crosstalk is regulated in part by Smad4-mediated signaling within the epithelium. SMAD4, TGFβ receptors, or BMP receptors are often mutated in colon cancer. This loss of TGFβ and/or BMP signaling likely facilitates epithelial-immune cell crosstalk in colitis-associated colon cancers.
Citation Format: Anna L. Means, Tanner J. Freeman, Connie J. Weaver, Chanjuan Shi, Mary K. Washington, Bronson C. Wessinger, Tasia Brown, David K. Flaherty, Kevin P. Weller, Robert J. Coffey, Keith T. Wilson, Robert D. Beauchamp. Smad4 pathways modulate induction of the chemokine Ccl20 and repress inflammation-induced carcinogenesis in mouse colon. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A16.
Abstract A30: Novel non-COX inhibitory sulindac derivative with PDE10 inhibitory activity reduces incidence and multiplicity of colorectal adenomas in the APC+/min-FCCC mouse model
Authors: Lee Kevin J. , Chen Xi , Valiyaveettil Jacob , Lindsey Ashley S. , Andrews Joel , Ramirez-Alcantara Veronica , Keeton Adam B. , Piazza Gary A. , Clapper Margie L. , Chang Wen-Chi L. 
Published: March 2017

Abstract
Sulindac has been reported to reduce the number and size of precancerous colonic adenomas in patients with familial adenomatous polyposis (FAP), but is not recommended for long-term use as a cancer chemopreventive drug because of potentially fatal toxicities associated with cyclooxygenase (COX) inhibition. We report here a novel sulindac derivative, ADT-061, that lacks COX-1 and COX-2 inhibitory activity, yet potently and selectively inhibits colon tumor cells with IC50 values of 0.3-0.5 μM with no significant effect on the growth of normal colonocytes. By comparison, sulindac sulfide inhibits colon tumor cell growth with IC50 values of 40-60 μM, and has only modest tumor cell selectivity. ADT-061 inhibits phosphodiesterase 10A (PDE10), which increases intracellular cGMP levels, thus activates protein kinase G, suppresses nuclear levels of β-catenin, and induces cell cycle arrest and apoptosis, all within the same concentration range that inhibits tumor cell growth. ADT-061was evaluated for chemopreventive activity in the APC+/min-FCCC mouse model of colon cancer, which harbors colorectal adenomas that express PDE10. Colonoscopy exams were initially performed on all mice to ensure the absence of colorectal adenomas prior to treatment. At 7-8 weeks of age, male mice were treated with ADT-061 (1000ppm and 1500ppm) in the diet for 14 weeks. ADT-061 reduced the incidence of colorectal adenomas from 95.8% in the control group to 73.9% in the 1000ppm group (p=0.048), and 59.1% (p=0.004) in the 1500ppm group. Control untreated mice had an average of 2.98 colorectal adenomas per mouse, while mice treated with 1000ppm and 1500ppm ADT-061 had an average of 2.04 (p=0.102) and 1.91 (p=0.039) adenomas per mouse, respectively. These observations suggest that ADT-061, or analogs thereof, merit further drug development efforts for colorectal cancer chemoprevention.
Citation Format: Kevin J. Lee, Xi Chen, Jacob Valiyaveettil, Ashley S. Lindsey, Joel Andrews, Veronica Ramirez-Alcantara, Adam B. Keeton, Gary A. Piazza, Margie L. Clapper, Wen-Chi L. Chang. Novel non-COX inhibitory sulindac derivative with PDE10 inhibitory activity reduces incidence and multiplicity of colorectal adenomas in the APC+/min-FCCC mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A30.
Abstract B14: TP53 synthetic lethal targets in colon cancer
Authors: Weige Charles C. , Liu Changlong , Anderson Erin L. , Banister Carolyn E. , Richardson Joseph , Contreras Carlo , Buckhaults Phillip J. 
Published: March 2017

Abstract
We have performed a genome-wide screen for pathways that are synthetic lethal with TP53 mutations in colon cancer. RKO colon cancer cells are wild type for TP53, and display robust p53-dependent growth arrest and apoptosis. We utilized an isogenic pair of RKO cells differing only in TP53 gene status (wild type vs homozygous null derivative) to screen a genome-wide GeCKO CRISPR library. After infection of these cells with the library and culturing for one week in vitro, we performed deep amplicon sequencing to identify CRISPR guide RNAs that were underrepresented in TP53 knockout cells. Multiple CRISPR guide RNAs targeting the CHEK1 and SHH genes were underrepresented in TP53 knockout cells. To validate these targets, we used CRISPR genome engineering to create an independent panel of six RKO clones with biallelic disruption of TP53, and tested small molecule inhibitors of CHEK1 (UCN01) and the SHH receptor SMO (Cyclopamine). TP53 null cells were tenfold more sensitive to UCN01, and 100-fold more sensitive to Cyclopamine, compared to TP53 wild type cells. Finally, the relevance of these findings to human colon cancers was confirmed by the establishment and treatment of colon cancer organoid avatars with either wild type or mutant TP53. Normal colon organoids, and tumor organoids with wild type TP53 were unaffected by either drug, whereas TP53 mutant organoids were significantly growth inhibited. Future studies will focus on testing these and additional targets, alone and in combination, against primary colon tumor and normal avatars and other preclinical models of TP53-mutant colon cancer.
Citation Format: Charles C. Weige, Changlong Liu, Erin L. Anderson, Carolyn E. Banister, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults. TP53 synthetic lethal targets in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B14.
Abstract B19: Disruption of energy homeostasis as an approach to block the proliferation of colon carcinomatosis
Authors: Bozzi Fabio , Mogavero Angela , Varinelli Luca , Gloghini Annunziata , Leoni Valerio , Beznoussenko Galina V. , Mironov Alexandre A. , Leo Ermanno , Pierotti Marco A. , Bongarzone Italia , Gariboldi Manuela 
Published: March 2017

Abstract
Strategies aimed at obtaining a complete cytoreduction are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc). We established organoid models that presented cancer stem cell characteristics from naïve CRC-pc surgical samples of two patients (C1 and C2). The organoids recapitulated their corresponding clinical samples in terms of 3D structure and immmunoistochemical profile and were enriched in LGR5 positive cancer stem cells. Proteomic analyses of organoids highlighted their strong dependence on energy producing pathways, suggesting that their targeting may be an effective therapeutic approach for the ablation of cancer cell malignancies. To test this hypothesis we treated organoids with an inhibitor of MIF/CD74 signaling axis, 4-iodo-6-phenylpyrimidine (4-IPP), and metformin, which inhibits mitochondrial oxidation. Both the drugs target metabolism acting on AMP-activated protein kinase (AMPK), the main regulator of cellular energy homeostasis. AMPK inhibits the major anabolic processes sustaining cancer cell proliferation and growth and confers cell plasticity to survive under conditions of metabolic stress, such as hypoxia and glucose deprivation, which is commonly observed in tumors with rapid growth. As a new finding we observed that treatment of organoids with 4-IPP resulted in decreased AMPK signaling activity, inducing a stress-signaling response and death of cultured organoids. Conversely, metformin treatment enhanced AMPK activation under energy stress, decreasing the activity of the anabolic factors ribosomal protein S6 and p4EBP-1 and inhibiting the mitochondrial activity, hindering cell proliferation. Furthermore, metformin treated organoids exhibited a Warburg-like metabolic profile. Our results show that organoid metabolism can be disrupted by metformin-induced AMPK activation but also through a strong reduction in AMPK functions caused by the removal of MIF/CD74 signaling axis that induces an irreversible disruption of energy homeostasis and ultimately causes cell death. Overall, we suggest that AMPK functions are crucial for energy metabolism of colorectal cancer peritoneal carcinomatosis, and regulation of AMPK activity could be a potential molecular target for the treatment of CRC-pc.
Citation Format: Fabio Bozzi, Angela Mogavero, Luca Varinelli, Annunziata Gloghini, Valerio Leoni, Galina V. Beznoussenko, Alexandre A. Mironov, Ermanno Leo, Marco A. Pierotti, Italia Bongarzone, Manuela Gariboldi. Disruption of energy homeostasis as an approach to block the proliferation of colon carcinomatosis. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B19.
Abstract B27: Serum uric acid levels as a prognostic factor in male patients with non-metastatic colorectal cancer
Authors: Rumi Shin , Won Park Ji , Woon Lee Dong , Seung-Bum Ryoo , Seung-Yong Jeong 
Published: March 2017

Abstract
Objective: Uric acid may be a marker of oxidative stress, and can be act as an antioxidant or a prooxidant. The role of serum uric acid (SUA) in the prognostic impact of cancer is controversial. This study aimed to evaluate whether the preoperative SUA level is associated with long-term outcomes in patients with colorectal cancer (CRC).
Methods: Between 2002 and 2010, 2,183 patients, who underwent curative surgical resection for non-metastatic CRC and had available SUA value, were included for this study. We analyzed the association between the overall survival (OS) and SUA level as quartile according to sex, using log-rank test and Cox proportional hazard regression to identify prognostic factors.
Results: Mean SUA level was different between male and female (male [n=1,328]: 5.320 ± 1.363, female [n=855]: 4.065 ± 1.180, p&lt;0.001). In female patients, there was no difference in OS according to SUA level. In male patients, SUA levels in the lowest quartile (&lt; 3.5 mg/dL) was associated with poor overall survival (5-year OS of SUA level &lt; 3.5 mg/dL vs ≥ 3.5 mg/dL: 72.0 % vs 97.1 %, p &lt; 0.001). SUA level was an independently significant prognostic factor (HR 1.714, 95% CI 1.306-2.250, p&lt;0.001).
Conclusion: Our results do not support the protective role of SUA in CRC cancer, and rather lower SUA concentrations to be associated with poor long-term outcomes in male CRC patients.
Citation Format: Shin Rumi, Park Ji Won, Lee Dong Woon, Ryoo Seung-Bum, Jeong Seung-Yong. Serum uric acid levels as a prognostic factor in male patients with non-metastatic colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B27.