bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Stress–Related Genetic Variants, Pro- and Antioxidant Intake and Status, and Advanced Prostate Cancer Risk
Authors: Geybels Milan S. , van den Brandt Piet A. , van Schooten Frederik J. , Verhage Bas A.J. 
Published: October 2014

AbstractBackground: Increased oxidative stress has been linked to prostate cancer. We investigated oxidative stress–related genetic variants in relation to advanced prostate cancer risk and examined potential interactions with pro- and antioxidant exposures.Methods: A case-cohort analysis was conducted in the prospective Netherlands Cohort Study, which included 58,279 men ages 55 to 69 years. Cohort members completed a baseline questionnaire and provided toenail clippings, which were used to isolate DNA. Advanced prostate cancer cases were identified during 17.3 years of follow-up. The analysis included 14 genetic variants and 11 exposures. Cox regression models were used for analysis and FDR Q-values were calculated.Results: Complete genotyping data were available for 952 cases and 1,798 subcohort members. CAT rs1001179 was associated with stage III/IV and stage IV prostate cancer risk, with HRs per minor allele of 1.16 [95% confidence intervals (CI), 1.01–1.33; P = 0.032] and 1.25 (95% CI, 1.07–1.46; P = 0.006), respectively. We tested 151 gene–environment interactions in relation to both stage III/IV and IV prostate cancer risk. Seven interactions were statistically significant after adjusting for multiple testing (FDR Q-value &lt;0.20); for stage III/IV prostate cancer, these involved intake of β-carotene (GPX1 rs17650792, hOGG1 rs1052133) and heme iron (GPX1 rs1800668 and rs3448), and for stage IV prostate cancer, these involved intake of catechin (SOD2 rs4880) and heme iron (hOGG1 rs1052133, SOD1 rs10432782).Conclusion: This study of advanced prostate cancer risk showed a marginal association with a CAT polymorphism and seven novel gene–environment interactions in the oxidative stress pathway.Impact: Oxidative stress–related genes and exposures may have a joint effect on advanced prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(1); 178–86. ©2014 AACR.
Modernizing the Diagnostic and Decision-Making Pathway for Prostate Cancer
Authors: Polascik Thomas J. , Passoni Niccolo' M. , Villers Arnauld , Choyke Peter L. 
Published: October 2014

Abstract
PSA has led to a drastic increase in the detection of prostate cancer, rendering this biomarker the gateway for the diagnostic pathway of prostatic neoplasms. However, the increase in incidence has not been mirrored by a similar reduction in mortality. Widespread PSA testing has facilitated the overdiagnosis and overtreatment of indolent disease. To reduce this phenomenon and avoid negative repercussions on the quality of life of men undergoing unnecessary therapies, the diagnostic pathway of prostate cancer needs to be improved. Multiparametric MRI (mp-MRI) can enhance the sensitivity and specificity of PSA, as well as the shortcomings of random biopsy sampling. This novel imaging technique has been proven to identify larger and more aggressive cancer foci, which should be targeted for treatment. New technological developments now allow for fusion of mp-MRI images with real-time ultrasound, opening the way to lesion-targeted biopsies. Furthermore, mp-MRI and targeted biopsies can also improve active surveillance protocols and permit more conservative focal therapy strategies. By implementing targeted biopsies, the diagnostic pathway will focus on clinically significant disease, consequently reducing overdiagnosis and overtreatment. Before this novel protocol becomes the new gold standard, mp-MRI acquisition and interpretation need to be standardized and targeted-biopsy strategies need to be further validated prior to abandoning random-sampling ones. Several multidisciplinary consortiums are already working on the standardization of prostate MRI, and there are ongoing prospective trials on targeted biopsies and MRI. Soon, imaging of prostatic lesions and selected biopsies will modify the diagnostic evaluation of prostate cancer, reducing overtreatment and therapy-derived complications that negatively affect quality of life. Clin Cancer Res; 20(24); 6254–7. ©2014 AACR.
Are We Nearing an Era of Chemotherapy-Free Management of Indolent Lymphoma?
Authors: Bachy Emmanuel , Salles Gilles 
Published: October 2014

Abstract
Indolent B-cell lymphomas are heterogeneous, comprising three grades of follicular lymphoma, small lymphocytic lymphoma, Waldenstöm macroglobulinemia, marginal zone lymphoma, and most recently, possibly low proliferative mantle cell lymphoma. These lymphomas are characterized by a high responsiveness to chemotherapy or immunochemotherapy; however, in most cases, conventional therapy might not offer a cure. Furthermore, the patient's age at diagnosis, at time to first or subsequent relapses, as well as potential comorbidities often preclude the use of chemotherapy. Recent progress has been made in our understanding of dysregulated pathways and immunologic antitumor responses in indolent lymphoma. Major therapeutic advances have been achieved in the development of nonchemotherapeutic agents, making “chemo-free” treatment a near-future reality. In this article, we highlight these promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs, with mAbs directed against other surface antigens such as CD22, with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling. However, the cost of such therapies and potential, albeit manageable, toxicity should be considered. Phase III trials will confirm the benefit of these new treatment strategies that do not require a chemotherapeutic drug and help us identify their exact place in the therapeutic armamentarium for indolent lymphoma. Here we focus on follicular lymphoma, which is the most frequent subtype of indolent lymphoma and for which an increasing body of evidence has emerged that supports the dawn of a new era of chemotherapy-free treatment.
See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”
Clin Cancer Res; 20(20); 5226–39. ©2014 AACR.
Putting the Clinical and Biological Heterogeneity of Non-Hodgkin Lymphoma into Context
Authors: O'Connor Owen A. , Tobinai Kensei 
Published: October 2014

Abstract
The lymphomas represent one of the most heterogeneous groups of malignancies in all of cancer medicine. Whether one attempts to understand these diseases in the context of their complicated ontogeny, unique biologic features, or clinical presentation, this heterogeneity has been a mixed blessing. On the one hand, it has created an ever-changing way to classify these diseases, as classification schemes have been compelled to reflect the rapidly emerging information that seems to split the disease into smaller and smaller subtypes. On the other hand, the biologic and clinical dissection of these diseases has allowed for the identification of unique biologic features—features that have led to novel targets and generated a plethora of new drugs. Virtually every subtype of non-Hodgkin lymphoma has benefited from these efforts to understand the biology of the different subtypes. This paradigm has led to new clinical trials that tailor novel drug regimens to specific biologic disease subtypes. As a prelude to this CCR Focus section, we attempt to put this evolving heterogeneity into context, bridging historical and modern-day views of classification of these diseases. Then, some of the world's leading lymphoma researchers share their perspectives on how to formulate new concepts of care in this era of biologic discovery. Over a relatively short time, the advances in lymphoma research have been nothing short of stunning. There now seems to be little doubt that these recent breakthroughs will redound favorably on the majority of patients diagnosed with a lymphoproliferative malignancy.
See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”
Clin Cancer Res; 20(20); 5173–81. ©2014 AACR.
New Paradigms in Mantle Cell Lymphoma: Is It Time to Risk-Stratify Treatment Based on the Proliferative Signature?
Authors: Dreyling Martin , Ferrero Simone , Vogt Niklas , Klapper Wolfram 
Published: October 2014

Abstract
The elucidation of crucial biologic pathways of cell survival and proliferation has led to the development of highly effective drugs, some of which have markedly improved mantle cell lymphoma (MCL) therapeutic opportunities in the past 10 years. Moreover, an undeniable clinical heterogeneity in treatment response and disease behavior has become apparent in this neoplasm. Thus, the need for biologic markers stratifying patients with MCL in risk classes deserving different treatment approaches has recently been fervently expressed. Among several newly discovered biomarkers, the dismal predictive value of a high proliferative signature has been broadly recognized in large studies of patients with MCL. Different techniques have been used to assess tumor cell proliferation, including mitotic index, immunostaining with Ki-67 antibody, and gene expression profiling. Ki-67 proliferative index, in particular, has been extensively investigated, and its negative impact on relapse incidence and overall survival has been validated in large prospective clinical trials. However, one important pitfall limiting its widespread use in clinical practice is the reported interobserver variability, due to the previous lack of a standardized approach for quantification among different laboratories. In the present review, we describe some of the major techniques to assess cell proliferation in MCL, focusing in particular on the Ki-67 index and its need for a standardized approach to be used in multicenter clinical trials. The value of MCL biologic prognostic scores (as MIPI-b) is discussed, along with our proposal on how to integrate these scores in the planning of future trials investigating a tailored therapeutic approach for patients with MCL.
See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”
Clin Cancer Res; 20(20); 5194–206. ©2014 AACR.
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis
Authors: Jilaveanu Lucia B. , Parisi Fabio , Barr Meaghan L. , Zito Christopher R. , Cruz-Munoz William , Kerbel Robert S. , Rimm David L. , Bosenberg Marcus W. , Halaban Ruth , Kluger Yuval , Kluger Harriet M. 
Published: October 2014

Abstract
Purpose: Approximately 40% of patients with metastatic melanoma develop brain metastases. Our purpose was to identify genes aberrantly expressed in melanoma that might be associated with propensity for brain homing.
Experimental Design: We studied gene expression profiles in a cell line model of brain metastasis (cerebrotropic A375Br cells vs. parental A375P cells) and compared them with profiles of patients who developed early brain metastases and who did not. A tissue microarray containing 169 metastatic melanoma cases with variable time to brain metastasis was constructed to further study marker expression by quantitative immunofluorescence. An in vitro model of the blood brain barrier (BBB) was generated to evaluate potential mediators of brain metastases.
Results: PLEKHA5 was differentially expressed in both the A375 cell line model and patient samples subjected to gene expression profiling. At the protein level, by quantitative immunofluorescence, PLEKHA5 was associated with decreased brain metastasis-free survival. PLEKHA5 overexpression was not associated with other metastatic sites. Knockdown of PLEKHA5 decreases the viability of A375Br cells, inhibits BBB transmigration and invasion in vitro. Similar results were found with YUMUL cells, cultured from a patient with overwhelming brain metastases. PLEKHA5 knockdown did not affect the viability of A375P cells.
Conclusions: PLEKHA5 expression in melanoma tumors was associated with early development of brain metastases. Inhibition of PLEKHA5 might decrease passage across the BBB and decrease proliferation and survival of melanoma cells both in the brain and in extracerebral sites. Clin Cancer Res; 21(9); 2138–47. ©2014 AACR.
See related commentary by Eisele et al., p. 1978
In Vivo Quantification of Hypoxic and Metabolic Status of NSCLC Tumors Using [18F]HX4 and [18F]FDG-PET/CT Imaging
Authors: Zegers Catharina M.L. , van Elmpt Wouter , Reymen Bart , Even Aniek J.G. , Troost Esther G.C. , Öllers Michel C. , Hoebers Frank J.P. , Houben Ruud M.A. , Eriksson Jonas , Windhorst Albert D. , Mottaghy Felix M. , De Ruysscher Dirk , Lambin Philippe 
Published: October 2014

Abstract
Purpose: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non–small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.
Experimental Design: FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio &gt; 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) &gt; 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake.
Results: At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm3 of the HX4-HV was outside the FDG–HV; for 37%, this volume was 1.9 to 12 cm3. Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV.
Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment. Clin Cancer Res; 20(24); 6389–97. ©2014 AACR.
Granulin–Epithelin Precursor Renders Hepatocellular Carcinoma Cells Resistant to Natural Killer Cytotoxicity
Authors: Cheung Phyllis F.Y. , Yip Chi Wai , Wong Nicholas C.L. , Fong Daniel Y.T. , Ng Linda W.C. , Wan Angus M.Y. , Wong Chun Kwok , Cheung Tan To , Ng Irene O.L. , Poon Ronnie T.P. , Fan Sheung Tat , Cheung Siu Tim 
Published: October 2014

Abstract
Immunoevasion is an emerging hallmark of cancer. Impairment of natural killer (NK) cytotoxicity is a mechanism to evade host immunosurveillance. Granulin–epithelin precursor (GEP) is a hepatic oncofetal protein regulating growth, invasion, and chemoresistance in hepatocellular carcinoma (HCC). We examined the role of GEP in conferring HCC cells the ability to evade NK cytotoxicity. In HCC cell lines, GEP overexpression reduced, whereas GEP suppression enhanced sensitivity to NK cytotoxicity. GEP downregulated surface expression of MHC class I chain–related molecule A (MICA), ligand for NK stimulatory receptor NK group 2 member D (NKG2D), and upregulated human leukocyte antigen-E (HLA-E), ligand for NK inhibitory receptor CD94/NKG2A. Functionally, GEP augmented production of soluble MICA, which suppressed NK activation. Matrix metalloproteinase (MMP)2 and MMP9 activity was involved partly in the GEP-regulated MICA shedding from HCC cells. In primary HCCs (n = 80), elevated GEP (P &lt; 0.001), MICA (P &lt; 0.001), and HLA-E (P = 0.089) expression was observed when compared with those in nontumor (n = 80) and normal livers (n = 10). Serum GEP (P = 0.010) and MICA (P &lt; 0.001) levels were higher in patients with HCC (n = 80) than in healthy individuals (n = 30). High serum GEP and/or MICA levels were associated with poor recurrence-free survival (log-rank test, P = 0.042). Importantly, GEP blockade by mAbs sensitized HCC cells to NK cytotoxicity through MICA. In summary, GEP rendered HCC cells resistant to NK cytotoxicity by modulating MICA expression, which could be reversed by GEP blockade using antibody. Serum GEP and MICA levels are prognostic factors and can be used to stratify patients for targeted therapy. Cancer Immunol Res; 2(12); 1209–19. ©2014 AACR.
Infection After Intracerebral Hemorrhage
Authors: Lord Aaron S. , Langefeld Carl D. , Sekar Padmini , Moomaw Charles J. , Badjatia Neeraj , Vashkevich Anastasia , Rosand Jonathan , Osborne Jennifer , Woo Daniel , Elkind Mitchell S.V. 
Published: October 2014

Background and Purpose—
Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes.

Methods—
We determined prevalence of infections in a multicenter, triethnic study of ICH. We performed univariate and multivariate analyses to determine the association of infection with admission characteristics and hospital complications. We performed logistic regression on association of infection with outcomes after controlling for known determinants of prognosis after ICH (volume, age, infratentorial location, intraventricular hemorrhage, and Glasgow Coma Scale).

Results—

Among 800 patients, infections occurred in 245 (31%). Admission characteristics associated with infection in multivariable models were ICH volume (odds ratio [OR], 1.02/mL; 95% confidence interval [CI], 1.01–1.03), lower Glasgow Coma Scale (OR, 0.91 per point; 95% CI, 0.87–0.95), deep location (reference lobar: OR, 1.90; 95% CI, 1.28–2.88), and black race (reference white: OR, 1.53; 95% CI, 1.01–2.32). In a logistic regression of admission and hospital factors, infections were associated with intubation (OR, 3.1; 95% CI, 2.1–4.5), dysphagia (with percutaneous endoscopic gastrostomy: OR, 3.19; 95% CI, 2.03–5.05 and without percutaneous endoscopic gastrostomy: OR, 2.11; 95% CI, 1.04–4.23), pulmonary edema (OR, 3.71; 95% CI, 1.29–12.33), and deep vein thrombosis (OR, 5.6; 95% CI, 1.86–21.02), but not ICH volume or Glasgow Coma Scale. Infected patients had higher discharge mortality (16% versus 8%;
P
=0.001) and worse 3-month outcomes (modified Rankin Scale ≥3; 80% versus 51%;
P
<0.001). Infection was an independent predictor of poor 3-month outcome (OR, 2.6; 95% CI, 1.8–3.9).

Conclusions—
There are identifiable risk factors for infection after ICH, and infections predict poor outcomes.
Comparison of the Tada Formula With Software Slicer
Authors: Xu Xinghua , Chen Xiaolei , Zhang Jun , Zheng Yi , Sun Guochen , Yu Xinguang , Xu Bainan 
Published: October 2014

Background and Purpose—
The Tada (ABC/2) formula has been used widely for volume assessment of intracerebral hematoma. However, the formula is crude for irregularly shaped hematoma. We aimed to compare the accuracy of the ABC/2 formula with open source software Slicer.

Methods—
Computed tomographic images of 294 patients with spontaneous intracerebral hematoma were collected. Hematoma volumes were assessed with the ABC/2 formula and calculated with software 3D Slicer. Results of these 2 methods were compared with regard to hematoma size and shape.

Results—

The estimated hematoma volume was 58.41±37.83 cm
3
using the ABC/2 formula, compared with 50.38±31.93 cm
3
with 3D Slicer (mean percentage deviation, 16.38±9.15%). When allocate patients into groups according to hematoma size, the mean estimation error were 3.24 cm
3
(17.72%), 5.85 cm
3
(13.72%), and 15.14 cm
3
(17.48%) for groups 1, 2, and 3, respectively. When divided by shape, estimation error was 3.33 cm
3
(9.76%), 7.19 cm
3
(18.37%), and 29.39 cm
3
(39.12%) for regular, irregular, and multilobular hematomas.

Conclusions—
There is significant estimation error using the ABC/2 formula to calculate hematoma volume. Compared with hematoma size, estimation error is more significantly associated with hematoma shape.
Behavioural induction of unreceptivity to mating from a post-copulatory display in the red mason bee, Osmia bicornis
Authors: Seidelmann K. 
Published: October 2014

In monandrous species, females have to manage their mating receptivity not only to gather an appropriate sperm supply, but to avoid further male sexual harassment as well. The shutdown of female receptivity to mating is often an irreversible process and therefore should result from a reliable signal. Females of the red mason bee, Osmia bicornis (syn. O. rufa), mate only once within the first day after their emergence from the maternal nest. The unreceptivity to mating of a mated female is induced by a male post-copulatory display, which takes place for about 10 min after ejaculating. During this display the male obviously applies an anti-aphrodisiac that reduces female’s attractiveness resulting in protection from other rival male sexual harassment. Protection by odour is only temporarily needed because females eventually reduce their attractiveness and receptivity to mating by themselves within a few days after emergence. The autonomous decrease in virgin female’s receptivity to mating is simply age driven and independent from mating status. In summary, the involvement of ejaculate substances in causing a loss of female receptivity to mating can be excluded for this species.
For Pilgrims and for Trade
Authors: Pétriat Philippe 
Published: October 2014

This article argues that public works were a major field where local notables associated themselves with Ottoman plans during the Tanzimat period. The documents this article is built on aim at evidencing the very tangible aspect of Ottomanization when imperial interests matched local ones.
First, plans for urban modernization were wisely endorsed by the main merchants of Jeddah to enhance the port facilities. Second, Ottoman archives highlight how important this local support was for the imperial administration. The matching of imperial and local interests is conspicuous in the common language used in minutes of the city council’s sessions and the petitions dispatched to Istanbul by the merchants of Jeddah. It exemplifies how notables advocated their own scheme of public planning and made it fit the politics of Ottomanization by framing their requests in terms of two important motivations for Ottoman officials: the proceedings of the pilgrimage, and trade.
A new species of Myrceugenia (Myrteae, Myrtaceae) from Distrito Federal, Brazil, with notes on its micromorphology
Authors: Gomes-Bezerra Kadja Milena , Faria Jair Eustáquio , Landrum Leslie , Soares-Silva Lucia Helena 
Published: October 2014

During field collections for the doctoral thesis of the first author, a population of Myrceugenia was found in a gallery forest along Bananal stream in the Distrito Federal, Brazil. This population was recognized as a new species related to Myrceugenia glaucescens and M. acutata, separated by 800 km or more from previously known populations of those species in Rio de Janeiro, Paraná, Santa Catarina and Rio Grande do Sul states. Specimens were studied using scanning electron microscopy (SEM) and the leaf architeture was studied in diaphanized leaves.