bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Impact of Comorbidity among Long-Term Breast Cancer Survivors: Results from the LACE Study
Authors: Braithwaite Dejana , Moore Dan H. , Satariano William A. , Kwan Marilyn L. , Hiatt Robert A. , Kroenke Candyce , Caan Bette J. 
Published: July 2012

Abstract
Background: Little is known about the long-term impact of comorbidity among women with breast cancer.
Methods: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models.
Results: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13–1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19–2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93–1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20–1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10–2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03–2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26–2.16 vs. stage III, HR, 0.53; 95% CI, 0.23–1.25).
Conclusion: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer–specific survival.
Impact: Comorbidity may play an important role in breast cancer outcomes. Cancer Epidemiol Biomarkers Prev; 21(7); 1115–25. ©2012 AACR.
Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Esophageal Cancer: A Systematic Review and Meta-analysis
Authors: Chen Meilan , Cai Erhui , Huang Jizheng , Yu Ping , Li Ke 
Published: July 2012

AbstractBackground: VEGF is a prime mediator of tumorigenesis and metastasis. Various studies assessing the prognostic value of VEGF in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the evidence on the suitability of VEGF to predict patients' survival.Methods: Searches were applied to PubMed and EMBASE until December 31, 2011, without language restrictions. Studies were assessed for quality using REMARK (Reporting recommendations for tumor MARKer prognostic studies). Data were collected comparing overall survival in patients with high VEGF level with those with low level. We conducted a systematic review of 31 studies (n = 2,387 patients) and completed a meta-analysis of 30 studies (n = 2,345 patients) that correlated VEGF levels with overall survival. Data were synthesized with HRs.Results: The estimated risk of death was 1.82-fold greater in patients with high VEGF expression [95% confidence interval (CI), 1.58–2.08]. The heterogeneity was not significant (P = 0.130) between studies. High VEGF expression was associated with worse survival in esophageal squamous cell carcinoma (HR, 1.81; 95% CI, 1.57–2.10) and there was no significance in between-study heterogeneity (P = 0.185). Data collected were not sufficient to determine the prognostic value of VEGF in patients with esophageal adenocarcinoma.Conclusions: In this meta-analysis, elevated VEGF expression was associated with poor survival in patients with esophageal cancer but not esophageal adenocarcinoma.Impact: These results support further investigation of VEGF expression for predicting poor survival in patients with esophageal carcinoma and may have implications for treatments directed at inhibiting VEGF-mediated angiogenesis. Cancer Epidemiol Biomarkers Prev; 21(7); 1126–34. ©2012 AACR.
Modeling of the Growth Kinetics of Occult Breast Tumors: Role in Interpretation of Studies of Prevention and Menopausal Hormone Therapy
Authors: Santen Richard J. , Yue Wei , Heitjan Daniel F. 
Published: July 2012

Abstract
Background: Autopsy studies report a reservoir of small, occult, undiagnosed breast cancers in up to 15.6% of women dying from unrelated causes. The effective doubling times (EDT) of these occult neoplasms range from 70 to 350 days and mammographic detection threshold diameters from 0.88 to 1.66 cm. Modeling of the biologic behavior of these occult tumors facilitates interpretation of tamoxifen breast cancer prevention and menopausal hormone therapy studies.
Methods: We used iterative and mathematical techniques to develop a model of occult tumor growth (OTG) whose parameters included prevalence, EDT, and detection threshold. The model was validated by comparing predicted with observed incidence of breast cancer in several populations.
Results: Iterative analysis identified a 200-day EDT, 7% prevalence and 1.16 cm detection threshold as optimal parameters for an OTG model as judged by comparison with Surveillance Epidemiology and End Results (SEER) population incidence rates in the United States. We validated the model by comparing predicted incidence rates with those observed in five separate population databases, in three long-term contralateral breast cancer detection studies, and with data from a computer-simulated tumor growth (CSTG) model. Our model strongly suggests that breast cancer prevention with anti-estrogens or aromatase inhibitors represents early treatment not prevention. In addition, menopausal hormone therapy does not primarily induce de novo tumors but promotes the growth of occult lesions.
Conclusions: Our OGTG model suggests that occult, undiagnosed tumors are prevalent, grow slowly, and are the biologic targets of anti-estrogen therapy for prevention and hormone therapy for menopausal women. Cancer Epidemiol Biomarkers Prev; 21(7); 1038–48. ©2012 AACR.
Height, Sitting Height, and Leg Length in Relation with Breast Cancer Risk in the E3N Cohort
Authors: Fagherazzi Guy , Vilier Alice , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Mesrine Sylvie 
Published: July 2012

Abstract
Background: If height is a well-established risk factor for breast cancer, leg length and sitting height are usually considered as better candidate biomarkers of growth hormone exposure than height, respectively, in pre- and postpuberty.
Methods: Risk of breast cancer associated with quartiles of height, sitting height, and leg length were estimated in the French E3N cohort (N = 50,704, including 2,065 breast cancer cases), stratified on both menopausal and hormone receptor statuses.
Results: Height was associated with an increased postmenopausal breast cancer risk [HR = 1.22 (1.06–1.41) when comparing extreme categories, Ptrend = 0.002], which was exclusively driven by the association with leg length [HR = 1.21 (1.05–1.39), Ptrend = 0.013] and not sitting height [HR = 1.03 (0.89–1.18), Ptrend = 0.379]. Leg length was associated with an increased ER+ breast cancer risk in postmenopausal [HR = 1.24 (1.06–1.46), Ptrend = 0.004], whereas sitting height was associated with a borderline decreased ER− premenopausal breast cancer risk [HR = 0.45 (0.20–1.01), Ptrend = 0.011]. The positive associations observed in the overall population between leg length and breast cancer risk were actually restricted to women who had a short birth length [HR = 1.82 (1.22–2.72), Ptrend = 0.022] and those with a low birth weight [HR = 1.43 (1.00–2.04), Ptrend = 0.054].
Conclusion: The two components of height risk are differentially associated with breast cancer risk: leg length with an increased risk of postmenopausal ER+ tumors and sitting height with a decreased risk of premenopausal ER− tumors.
Impact: Future prospective studies should no longer consider height a single risk factor for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1171–5. ©2012 AACR.
Oophorectomy after Menopause and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers
Authors: Kotsopoulos Joanne , Lubinski Jan , Lynch Henry T. , Kim-Sing Charmaine , Neuhausen Susan , Demsky Rochelle , Foulkes William D. , Ghadirian Parviz , Tung Nadine , Ainsworth Peter , Senter Leigha , Karlan Beth , Eisen Andrea , Eng Charis , Weitzel Jeffrey , Gilchrist Dawna M. , Blum Joanne L. , Zakalik Dana , Singer Christian , Fallen Taya , Ginsburg Ophira , Huzarski Tomasz , Sun Ping , Narod Steven A. 
Published: July 2012

Abstract
Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers.
Methods: We conducted a matched case–control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates.
Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ = −0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend &lt; 0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40–0.66; Ptrend &lt; 0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62–1.07; Ptrend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02–0.54; P = 0.006).
Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer.
Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention. Cancer Epidemiol Biomarkers Prev; 21(7); 1089–96. ©2012 AACR.
Urinary Naphthol Metabolites and Chromosomal Aberrations in 5-Year-Old Children
Authors: Orjuela Manuela A. , Liu Xinhua , Miller Rachel L. , Warburton Dorothy , Tang Deliang , Jobanputra Vaidehi , Hoepner Lori , Suen Ida Hui , Diaz-Carreño Silvia , Li Zheng , Sjodin Andreas , Perera Frederica P. 
Published: July 2012

Abstract
Background: Exposure to naphthalene, an International Agency for Research on Cancer (IARC)-classified possible carcinogen and polycyclic aromatic hydrocarbon (PAH), is widespread, though resulting health effects are poorly understood. Metabolites of naphthalene, 1- and 2-naphthol, are measurable in urine and are biomarkers of personal exposure. Chromosomal aberrations, including translocations, are established markers of cancer risk and a biodosimeter of clastogenic exposures. Although prenatal (maternal) PAH exposure predicts chromosomal aberrations in cord blood, few studies have examined chromosomal aberrations in school-age children and none has examined their association with metabolites of specific PAHs.
Methods: Using Whole Chromosome Paint Fluorescent in situ Hybridization, we documented chromosomal aberrations including translocations, in 113 five-year-old urban minority children and examined their association with concurrent concentrations of PAH metabolites measured in urine.
Results: We report that in lymphocytes, the occurrence and frequency of chromosomal aberrations including translocations are associated with levels of urinary 1- and 2-naphthol. When doubling the levels of urinary naphthols, gender-adjusted OR for chromosomal aberrations are 1.63 [95% confidence interval (CI), 1.21–2.19] and 1.44 (95% CI, 1.02–2.04) for 1- and 2-naphthol, respectively; and for translocations OR = 1.55 (95% CI, 1.11–2.17) and 1.92 (95% CI, 1.20–3.08) for 1- and 2-naphthol, respectively.
Conclusion: Our results show that markers of exposure to naphthalene in children are associated with translocations in a dose-related manner, and that naphthalene may be a clastogen.
Impact: Indoor exposure to elevated levels of naphthalene is prevalent in large regions of the world. This study is the first to present an association between a marker of naphthalene exposure and a precarcinogenic effect in humans. Cancer Epidemiol Biomarkers Prev; 21(7); 1191–202. ©2012 AACR.
Differentiation Between Fresh and Old Left Ventricular Thrombi by Deformation Imaging
Authors: Niemann Markus , Gaudron Philipp Daniel , Bijnens Bart , Störk Stefan , Beer Meinrad , Hillenbrand Hanns , Cikes Maja , Herrmann Sebastian , Hu Kai , Ertl Georg , Weidemann Frank 
Published: July 2012

Background—
Noninvasive echocardiographic differentiation between old and fresh left ventricular thrombi after myocardial infarction would be of clinical importance to estimate the risk for embolization and the necessity of anticoagulation.

Methods and Results—

Fifty-two patients, aged 41 to 87 years, with a thrombus after myocardial infarction were included in this 2-part study: In substudy-I, 20 patients, 10 each with a definite diagnosis of fresh or old thrombus, were included. In the subsequent prospective substudy-II, 32 consecutive patients with an incident thrombus after myocardial infarction but unknown thrombus age were started on phenprocoumon and followed for 6 months. Data on medical history, standard echocardiography, strain-rate (SR) imaging and magnetic resonance tomography were analyzed. In substudy-I, analysis of thrombus deformation revealed the most rapid change in SR during the isovolumetric relaxation period when cavity pressure decreases rapidly. Fresh (range: 5–27 days) and old thrombi (4–26 months) could be discriminated without overlap by peak SR during the isovolumetric relaxation period, using a cutoff value of 1 s
−1
. Applying this threshold value in substudy-II, 17 thrombi were echocardiographically classified as fresh (=SR ≥1 s
−1
) and 15 as old. After 6 months in the fresh thrombus group, 16 of 17 thrombi had disappeared (94%), and in 1 patient the thrombus size was diminished by >50% (now presenting an old thrombus SR pattern). In contrast, 14 of the 15 old thrombi remained unchanged in size and deformation (1 thrombus disappeared).

Conclusions—
Fresh and old intracavitary thrombi can be reliably differentiated by deformation imaging. In fresh thrombi, anticoagulation with phenprocoumon results in thrombus resolution in most patients.
Transplantation and Tracking of Human-Induced Pluripotent Stem Cells in a Pig Model of Myocardial Infarction
Authors: Templin Christian , Zweigerdt Robert , Schwanke Kristin , Olmer Ruth , Ghadri Jelena-Rima , Emmert Maximilian Y. , Müller Ennio , Küest Silke M. , Cohrs Susan , Schibli Roger , Kronen Peter , Hilbe Monika , Reinisch Andreas , Strunk Dirk , Haverich Axel , Hoerstrup Simon , Lüscher Thomas F. , Kaufmann Philipp A. , Landmesser Ulf , Martin Ulrich 
Published: July 2012

Background—
Evaluation of novel cellular therapies in large-animal models and patients is currently hampered by the lack of imaging approaches that allow for long-term monitoring of viable transplanted cells. In this study, sodium iodide symporter (NIS) transgene imaging was evaluated as an approach to follow in vivo survival, engraftment, and distribution of human-induced pluripotent stem cell (hiPSC) derivatives in a pig model of myocardial infarction.

Methods and Results—

Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NIS
pos
-hiPSCs) were established. Iodide uptake, efflux, and viability of NIS
pos
-hiPSCs were assessed in vitro. Ten (±2) days after induction of myocardial infarction by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NIS
pos
-hiPSCs guided by 3-dimensional NOGA mapping was performed. Dual-isotope single photon emission computed tomographic/computed tomographic imaging was applied with the use of
123
I to follow donor cell survival and distribution and with the use of
99m
TC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NIS
pos
-hiPSCs was increased 100-fold above that of nontransgenic controls. In vivo, viable NIS
pos
-hiPSCs could be visualized for up to 15 weeks. Immunohistochemistry demonstrated that hiPSC-derived endothelial cells contributed to vascularization. Up to 12 to 15 weeks after transplantation, no teratomas were detected.

Conclusions—

This study describes for the first time the feasibility of repeated long-term in vivo imaging of viability and tissue distribution of cellular grafts in large animals. Moreover, this is the first report demonstrating vascular differentiation and long-term engraftment of hiPSCs in a large-animal model of myocardial infarction. NIS
pos
-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models.
Theoretical Impact of Changing Albedo on Precipitation at the Southernmost Boundary of the ITCZ in South America
Authors: Doughty Christopher E. , Loarie Scott R. , Field Christopher B. 
Published: July 2012

AbstractSouth America has undergone a large increase in albedo over the past decade as forests have been converted to crops and wetlands have been drained. Recent modeling literature and paleoclimate precipitation proxies have highlighted how changes in surface energy balance could affect the position of the intertropical convergence zone (ITCZ) in South America. Here, the authors investigate whether large continental increases in albedo in South America can likewise affect the southward migration of the ITCZ into South America using the NCAR Community Atmosphere Model, version 3.0 (CAM3.0) coupled with the Community Land Model, version 3.5 (CLM3.5) and a slab ocean model. Moderate Resolution Imaging Spectroradiometer (MODIS) albedo data show that between 2001 and 2008 average albedo increased by 0.0025 albedo units across all South America and by 0.0032 albedo units between 0° and 24° latitude in South America and, because of this effect, the authors’ simulations estimate an average ~23 mm yr−1 decrease in rainfall in the southern migration of the ITCZ (SMI) and an average ~9 mm yr−1 decrease in the entire Amazon basin. Large increases in albedo in South America decrease the northward atmospheric energy transport at the equator during the months the region of increased albedo is south of the ITCZ (May–July), leading to an apparent delay in its arrival to the SMI region and reduced rainfall in this region. However, because changing albedo is often associated with changing surface roughness, the authors model this separately and find that decreased surface roughness will have an opposite, increasing effect on precipitation. Therefore, they expect increasing albedo in South America associated with the drainage of wetlands to decrease precipitation, especially in the SMI region; however, in the case of deforestation, some of the decrease in precipitation from increased albedo may be offset by a corresponding decrease in surface roughness.
Long-Term Trends in Air Temperature Distribution and Extremes, Growing Degree‐Days, and Spring and Fall Frosts for Climate Impact Assessments on Agricultural Practices in Nebraska
Authors: Skaggs Kari E. , Irmak Suat 
Published: July 2012

AbstractAir temperature influences agricultural practices and production outcomes, making detailed quantifications of temperature changes necessary for potential positive and negative effects on agricultural management practices to be exploited or mitigated. Temperature trends of long-term data for five agricultural locations, ranging from the subhumid eastern to the semiarid western parts of Nebraska, were studied to determine local temperature changes and their potential effects on agricultural practices. The study quantified trends in annual and monthly average maximum and minimum air temperature (Tmax and Tmin), daily temperature range (DTR), total growing degree-days, extreme temperatures, growing‐season dates and lengths, and temperature distributions for five heavily agricultural areas of Nebraska: Alliance, Central City, Culbertson, Fremont, and Hastings. July and August were the months with the greatest decreases in Tmax for the central part of Nebraska—Culbertson, Hastings, and Central City. Alliance, Culbertson, and Fremont had year-round decreases in DTR. Central City and Hastings experienced growing‐season decreases in DTR. Increases in growing‐season length occurred at rates of 14.3, 16.7, and 11.9 days century−1 for Alliance, Central City, and Fremont, respectively. At Hastings, moderately earlier last spring frost (LS) at a rate of 6.6 days century−1 was offset by an earlier (2.7 days century−1) first fall frost (FF), resulting in only a 3.8 days century−1 longer growing season. There were only slight changes in LS and FF dates of around 2 days earlier and 1 day later per century, respectively, for Culbertson.
Teaching the clinical encounter in psychiatry: a trial of Balint groups for medical students
Authors: Parker Stephen , Leggett Andrew 
Published: July 2012

Objective: Balint groups are being trialled as a method to facilitate understanding of the relational aspects of student encounters with psychiatric patients. This paper reports on the establishment, processes and trends in the student evaluations of these groups. Method: The groups have been introduced as part of the medical student curriculum at a tertiary referral hospital. In six of the eight weeks of the clinical rotation in psychiatry, students meet in a group led by the authors, to discuss relational aspects of their interactions with patients. Ten third-year postgraduate medical students participate in the group each rotation. The educational value of each meeting and the group overall is assessed using questionnaires. Results: The groups tended to be rated positively by the participants. However, students were less certain of the relevance to their clinical practice. Vignettes demonstrating aspects of group process are presented in the context of the leaders’ experiential account. Conclusions: Short-term clinical reflection groups can be effectively implemented for medical students in a hospital environment. These groups have the potential to support students in the process of learning to work in doctor–patient relationships, but may encounter significant challenges necessitating adaptation of method and process to context.
Thoughts of suicide and stage of recovery in patients with schizophrenia in community mental health care
Authors: Gale Christopher , Skegg Keren , Mullen Richard , Patterson Tess , Gray Andrew 
Published: July 2012

Objective: Suicidality among patients with schizophrenia remains a major concern. The consumer-oriented concept of recovery has been recognised as important in recent years. We aimed to assess whether there was any relationship between stages of recovery and suicidality among people with schizophrenia in community care. Method: In a community mental health service, 85 patients with schizophrenia consented to an interview during which their stages of recovery were assessed using the Stages of Recovery Instrument. They were asked about suicidality and screened for depression using the Revised Clinical Interview Schedule. Insight was assessed via the Insight and Treatment Attitudes Questionnaire. Data analysis involved logistic regression. Results: In the past year 14% of the patients reported having wanted to die and 13% had considered suicide. Scores indicating the highest stage of recovery were associated with lower odds of suicidal thoughts. In contrast, suicidality was not significantly associated with depression or stage of insight. Conclusion: The link found between suicidality and stages of recovery has practical implications for suicide prevention among those with schizophrenia in community care. Approaches that facilitate the recovery process may reduce suicidal thoughts in this population.