bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer‐aided breast MR image feature analysis for prediction of tumor response to chemotherapy
Authors: Aghaei Faranak , Tan Maxine , Hollingsworth Alan B. , Qian Wei , Liu Hong , Zheng Bin 
Published: October 2015

Purpose:To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy.Methods:The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer‐aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave‐one‐case‐out validation method.Results:In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN‐based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01).Conclusions:This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.
A cross-sectional study on the relationship of age, gestational age and HIV infection to bacterial vaginosis and genital mycoplasma infection
Authors: Redelinghuys Mathys J , Ehlers Marthie M , Dreyer Andries W , Lombaard Hennie , Olorunju Steve A S , Kock Marleen M 
Published: October 2015

ObjectivesPregnant women are especially at risk of developing complications when infected with reproductive tract infections (RTIs). The objective of this study was to determine the prevalence of bacterial vaginosis (BV) and genital mycoplasmas in pregnant women and investigate the associations between BV, genital mycoplasmas, HIV infection, age and gestational age.DesignCross-sectional study with descriptive and analytical components.SettingAntenatal clinic of a tertiary academic hospital in South Africa.Participants220 pregnant women older than 18 were included in the study and provided self-collected vaginal swabs.Primary and secondary outcomesBV and genital mycoplasma colonisation and/or infection in women of differing age, gestational period and HIV status.ResultsThe prevalence of BV was 17.7% (39/220) (95% CI 12.9 to 23.4), intermediate vaginal flora (IVF) 15% (33/220) (95% CI 10.56 to 20.42), and the overall prevalence of genital mycoplasmas was 84% (185/220) (95% CI 78.47 to 88.58). BV was significantly associated with HIV infection with an OR of 2.84 (95% CI 1.08 to 7.46 and p value=0.034). However, BV was inversely associated with gestational age with an OR of 0.08 (95% CI 0.01 to 0.42 and p value=0.003) for second trimester pregnancies and an OR of 0.03 (95% CI 0.01 to 0.17 and p value<0.001) for third trimester pregnancies using the first trimester as reference. IVF was significantly associated with HIV infection with an OR of 2.7 (95% CI 1.07 to 6.79 and p value=0.035) but not with age or gestational age. Genital mycoplasmas were not significantly associated with age, gestational age, HIV status, BV flora or IVF.ConclusionsThe high infection rate of genital mycoplasmas and the association of BV with HIV found in this study reiterate the importance of screening for these RTIs in high-risk groups such as pregnant women.
MRI and serum high-sensitivity C reactive protein predict long-term mortality in non-ischaemic cardiomyopathy
Authors: Sadahiro Taketaro , Kohsaka Shun , Okuda Shigeo , Inohara Taku , Shiraishi Yasuyuki , Kohno Takashi , Yoshikawa Tsutomu , Fukuda Keiichi 
Published: October 2015

ObjectiveMyocardial fibrosis related to non-specific inflammation can be detected using late gadolinium-enhancement cardiovascular MR (LGE-CMR), which is an important prognostic indicator for dilated cardiomyopathy (DCM). The aims of this study were to define the prognostic factors for DCM with LGE-CMR, and to evaluate the impact of the prognostic factors on adverse effects.MethodsWe performed a retrospective analysis of a prospectively maintained single centre registry. We analysed the data from 76 patients with DCM who had been admitted for acute heart failure. The primary combined end point was defined as all-cause mortality and rehospitalisation.ResultsLGE-CMR was present in 39 patients (51%), and the mean follow-up period was 813±54 days. The primary end point occurred in 20 patients (5 (13.5%) patients without LGE-CMR and 15 (38.5%) patients with LGE-CMR, p=0.006). Sixteen of 39 patients with LGE-CMR exhibited elevated high-sensitivity C reactive protein (hs-CRP >0.3 mg/dL). Patients with elevated hs-CRP and LGE-CMR had a significantly higher incidence of the primary end point compared with patients with normal hs-CRP and LGE-CMR (62.5%; 10 patients, 22.7%; 5 patients, respectively, p=0.001). Elevated hs-CRP was significantly associated with the primary end point (HR: 4.04; 95% CI 1.67 to 9.76; p=0.002). After elevated hs-CRP was adjusted for known predictors of DCM, it was still associated with the primary end point (HR: 2.91; 95% CI 1.19 to 7.15; p=0.02).ConclusionsAmong patients with DCM, LGE-CMR and elevated hs-CRP are associated with a higher incidence of the long-term combined end point of all-cause mortality and hospitalisation.Trial registration number:UMIN000001171.
Abstract A30: In vitro transformation of human primary epithelial cells by Myc
Authors: Dakic Aleksandra , Fang Shuang , Choudhury Sujata , Palechor-Ceron Nancy , Yu Songtao , Schlegel Richard , Liu Xuefeng 
Published: October 2015

Abstract
The Myc/Max/Mad network plays a critical role in cell proliferation, differentiation and apoptosis. Our previous data have shown that c-Myc is overexpressed in cervical cancer cell lines and that the HPV E6 oncoprotein in these cancer cells interacts with Myc both in vitro and in vivo. The consequence of these E6/Myc interactions results in the activation of telomerase and cell immortalization. Since the HPV E6/E7 genes cooperate to immortalize genital keratinocytes (both foreskin and cervical cells), we questioned whether Myc activation might be sufficient to replace E6 in cell immortalization. Our studies indicate that indeed Myc and E7 are sufficient to immortalize human genital keratinocytes. Surprisingly, the solitary transduction of Myc into cervical cells induced rapid cell death. These dying cells exhibited increased p53 expression and morphologic and biochemical characteristics of apoptosis. These results were also observed in human foreskin keratinocytes (when grown in commercially available, serum free medium) and suggest that the E7 protein counteracts the strong apoptotic activity of Myc. Myc-induced apoptosis in the genital keratinoctyes was observable as dramatic membrane blebbing. Since the Rho kinase (ROCK) inhibitor, Y-27632, has previously been shown to inhibit apoptosis in dissociated, detached stem cells, we tested whether it would inhibit membrane blebbing in Myc-expressing keratinoctyes and whether this might permit the establishment of Myc-driven keratinocyte cell lines. Within minutes, Y-27632 inhibited blebbing of Myc-expressing keratinocytes and reduced cell detachment. This activity is independent of expression of p53, pRB, and hTERT. More important, the use of Y-27632 allowed us to generate keratainocyte cell lines that were driven by overexpression of Myc. Our data suggest that immortalization and cell proliferation by Myc and Y-27632 are largely due to inhibition of apoptosis. An outgrowth of these studies is that we have screened for inhibitors of Myc-driven immortalization and found that two different HDAC inhibitors were able to induce cell death, including in established cervical carcinoma cell lines, and that cell death is paralleled by the down-regulation of Myc.
Citation Format: Aleksandra Dakic, Shuang Fang, Sujata Choudhury, Nancy Palechor-Ceron, Songtao Yu, Richard Schlegel, Xuefeng Liu. In vitro transformation of human primary epithelial cells by Myc. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A30.
Abstract A40: CD30: A therapeutic target of MYC-driven cancer
Authors: Gennaro Victoria , Zhang Xiao-yong , DeSalle Lauren , Yu Duonan , Thomas-Tikhonenko Andrei , McMahon Steven 
Published: October 2015

Abstract
The MYC oncogene induces a multitude of human malignancies and has been well characterized as a critical driver of select lymphoma subtypes. In MYC-amplified tumor progression, there is a robust dependence on MYC activity; however, strategies developed to modulate MYC function in cancer have yielded little success. Patients harboring these MYC-driven tumors would benefit from a directed therapy that circumvents explicit molecular targeting of MYC expression. Our preliminary data from an unbiased expression-profiling screen identified CD30 as a primary downstream target of the MYC oncoprotein. CD30 is a member of the tumor necrosis factor superfamily and resides on the extracellular membrane; it is highly expressed in many lymphomas while acutely restricted in normal cells. Within the last few decades, CD30 has emerged as a diagnostic marker and therapeutic target of many lymphoproliferative disorders and diseases. The biological function of CD30 is pleiotropic: CD30 stimulation is reportedly linked to cell cycle arrest, apoptosis, and proliferation through activation of the pro-survival transcription factor, NF-kB. However, the underlying mechanisms that regulate CD30 expression remain unclear. CD30-driven oncogenic pathways phenocopy those initiated by MYC, suggesting CD30's potential status as an effector of MYC-driven tumorigenic events. Here we report that CD30 is regulated at the transcriptional level by MYC. Through a genetic and biochemical approach, we define CD30 induction in a MYC-dependent manner across a variety of human cell lines of both lymphomagenic and non-lymphomagenic origin. Furthermore, in a murine lymphoma model where tumor formation is driven by a conditional allele of MYC, CD30 transcript levels are tightly correlated with MYC activity. Ultimately, CD30 induction offers a novel therapeutic avenue by which to target MYC-driven oncogenesis and has the potential to reshape detection and treatment of MYC-regulated cancer.
Citation Format: Victoria Gennaro, Xiao-yong Zhang, Lauren DeSalle, Duonan Yu, Andrei Thomas-Tikhonenko, Steven McMahon. CD30: A therapeutic target of MYC-driven cancer. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A40.
Abstract B40: Selective suppression of Myc transcription with a G-quadruplex stabilizing small molecule
Authors: Simmons John K. , Saunders Lindsey B. , Felsenstein Kenneth , Gareiss Peter , Zhang Shuling , Mock Beverly , Schneekloth John S. 
Published: October 2015

Abstract
The transcription factor Myc is disregulated in some 70% of human cancers, where it triggers aberrant growth and signaling, and contributes to tumorigenesis. Thus, Myc is a highly sought after drug target. However, targeting the Myc protein directly with small molecules has proven to be a significant challenge due to a lack of small molecule binding sites and rapid protein turnover in the cell. To date, most successes in inhibiting Myc function have come through alternative indirect approaches such as BET bromodomain inhibition. Here, we present a novel class of small molecules that silences Myc expression by stabilization of the G-quadruplex structure present in the NHEIII region of the Myc promoter. We used a small molecule microarray screen to identify molecules that selectively bind to the Myc G-quadruplex. Biophysical studies, including thermal melt and SPR analysis, demonstrated that the compound binds reversibly to the quadruplex structure with low micromolar affinity. Next, we demonstrated that the compound inhibited polymerase progression in an in vitro PCR-stop assay in a dose dependent fashion, while the compound had no effect on amplification of an oligo incapable of forming a quadruplex. Target specificity was demonstrated using a cell-based assay where one copy of the Myc gene has a translocation and is no longer under the control of a quadruplex. In this assay, Myc is only silenced upon treatment when there is a quadruplex in the promoter. Further studies demonstrate dose- and time-dependent effects on cell viability and Myc protein levels in a panel of myeloma cells. The compound also had minimal effects on viability of PBMCs from a healthy donor. Finally, gene expression analysis demonstrated that in contrast to other quadruplex-stabilizing small molecules, the compound reported here does not silence several other genes that are also under the control of quadruplexes.
Citation Format: John K. Simmons, Lindsey B. Saunders, Kenneth Felsenstein, Peter Gareiss, Shuling Zhang, Beverly Mock, John S. Schneekloth, Jr.. Selective suppression of Myc transcription with a G-quadruplex stabilizing small molecule. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B40.
Abstract IA16: Transcriptional regulation by physiological and oncogenic Myc levels
Authors: Eyss Bjoern von , Wolf Elmar , Wiese Katrin , Eilers Martin 
Published: October 2015

Abstract
Myc proteins bind globally to open promoters of all three RNA polymerases and in some instances globally enhance transcription. Surprisingly, Myc-driven tumor cells are characterized by specific gene expression profiles, which are defined by both activation and repression of specific target genes and which hold considerable prognostic value and biological information about tumor physiology.
One mechanism that contributes to this specificity is promoter affinity and functionally distinct classes of Myc target genes vary widely in their apparent affinity to Myc. As a result, physiological and supraphysiological/oncogenic levels of Myc regulate different gene expression programs. Furthermore, oncogenic levels of Myc engage the zinc finger protein, Miz1, to repress transcription and I will briefly review what we know about the mechanism of repression. I will discuss two examples how different levels of Myc sensitize cells towards apoptosis and regulate the self-renewing potential of adult stem cells.
Citation Format: Bjoern von Eyss, Elmar Wolf, Katrin Wiese, Martin Eilers. Transcriptional regulation by physiological and oncogenic Myc levels. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA16.
Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset
Authors: Seashore-Ludlow Brinton , Rees Matthew G. , Cheah Jaime H. , Cokol Murat , Price Edmund V. , Coletti Matthew E. , Jones Victor , Bodycombe Nicole E. , Soule Christian K. , Gould Joshua , Alexander Benjamin , Li Ava , Montgomery Philip , Wawer Mathias J. , Kuru Nurdan , Kotz Joanne D. , Hon C. Suk-Yee , Munoz Benito , Liefeld Ted , Dančík Vlado , Bittker Joshua A. , Palmer Michelle , Bradner James E. , Shamji Alykhan F. , Clemons Paul A. , Schreiber Stuart L. 
Published: October 2015

AbstractIdentifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2).Significance: We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses. Cancer Discov; 5(11); 1210–23. ©2015 AACR.See related commentary by Gray and Mills, p. 1130.This article is highlighted in the In This Issue feature, p. 1111
Long-Term Natural History of Adult Wolff–Parkinson–White Syndrome Patients Treated With and Without Catheter Ablation
Authors: Bunch T. Jared , May Heidi T. , Bair Tami L. , Anderson Jeffrey L. , Crandall Brian G. , Cutler Michael J. , Jacobs Victoria , Mallender Charles , Muhlestein Joseph B. , Osborn Jeffrey S. , Weiss J. Peter , Day John D. 
Published: October 2015

Background—
There are a paucity of data about the long-term natural history of adult Wolff–Parkinson–White syndrome (WPW) patients in regard to risk of mortality and atrial fibrillation. We sought to describe the long-term outcomes of WPW patients and ascertain the impact of ablation on the natural history.

Methods and Results—

Three groups of patients were studied: 2 WPW populations (ablation: 872, no ablation: 1461) and a 1:5 control population (n=11 175). Long-term mortality and atrial fibrillation rates were determined. The average follow-up for the WPW group was 7.9±5.9 (median: 6.9) years and was similar between the ablation and nonablation groups. Death rates were similar between the WPW group versus the control group (hazard ratio, 0.96; 95% confidence interval, 0.83–1.11;
P
=0.56). Nonablated WPW patients had a higher long-term death risk compared with ablated WPW patients (hazard ratio, 2.10; 95% confidence interval: 1.50–20.93;
P
<0.0001). Incident atrial fibrillation risk was higher in the WPW group compared with the control population (hazard ratio, 1.55; 95% confidence interval, 1.29–1.87;
P
<0.0001). Nonablated WPW patients had lower risk than ablated patients (hazard ratio, 0.39; 95% confidence interval, 0.28–0.53;
P
<0.0001).

Conclusions—
Long-term mortality rates in WPW patients are low and similar to an age-matched and gender-matched control population. WPW patients that underwent the multifactorial process of ablation had a lower mortality compared to nonablated WPW patients. Atrial fibrillation rates are high long-term, and ablation does not reduce this risk.
Comparison of Long-Term Outcomes in Real-World Patients Between Resolute Zotarilumus-Eluting and Paclitaxel-Eluting Stents in Small Vessel
Authors: Kilickesmez Kadriye Orta , Kocaş Betül , Yildiz Ahmet , Coskun Ugur , Ersanli Murat , Arat Alev , Gürmen Tevfik 
Published: October 2015

Objective: To compare the long-term clinical outcomes between Resolute zotarolimus-eluting stent (R-ZES) and paclitaxel-eluting stent (PES) in patients with small coronary artery disease. Background: Patients with a small vessel diameter are independently associated with increased risk of adverse cardiac events after drug-eluting stent implantation. Methods: A cohort of 265 patients treated with R-ZES (185 patients with 211 lesions) or PES (80 patients with 100 lesions) in small vessel (≤2.5 mm) lesions were retrospectively analyzed. The primary end point of the study was the composite of major adverse cardiac events. The secondary end points included target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis at 3 years. Results: The baseline characteristics were similar between the 2 groups. In the R-ZES group, the mean stent diameter was smaller and the total stent length per lesion was longer. Major adverse cardiac events occurred in 8 (10%) patients who had received PES and in 7 (3.8%) patients who had received R-ZES ( P = .07). The rates of 3-year TLR (2.2% vs 2.5%; P = 1.00) and TVR (5.4% vs 10.0%; P = .17) showed no statistically significant difference between the R-ZES and PES groups. The rate of stent thrombosis was 0.5% in the R-ZES group and 2.5% in the PES group ( P = .21). Conclusion: The rates of major adverse cardiac events and cardiac death were similar in the R-ZES-treated group compared with the PES-treated group.
Gianantonio Tadini and falling bodies: A new documentary source for the reconstruction of the history of experimental proofs on the Earth’s rotation
Authors: Giannini Giulia 
Published: October 2015

Gianantonio Tadini (1754–1830) is the little known protagonist in an important experiment carried out in Bergamo between 1794 and 1795. Based on the measurement of the deviation of a falling body, the experiment owes much to the one that was conducted by Giambattista Guglielmini (1760–1817) in Bologna in 1791, which aimed at demonstrating Earth’s rotation. Tadini’s experimental work represents the most successful attempt carried out before the 19th century, and it led to the first correct formulation of deviation’s measurement. In spite of this, it is not well represented in the general literature on the history of experiments intended to show diurnal Earth’s motion.1 The discovery of Tadini’s diary of experiments as well as some notes and a part of his correspondence – preserved as manuscripts in the Angelo Mai municipal library in Bergamo – allows us now to reconstruct the history of Tadini’s experiment and of his reasoning about Guglielmini’s work. In this paper, I describe the genesis and the development of Tadini’s experiment, clarify the role played by the different personalities involved and set these trials against the background of the widest history of proofs on diurnal Earth’s rotation carried out in Europe in those years.