bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Expression of PTEN, Insulin-Like Growth Factor I Receptor (IGF-IR), and Lethal Prostate Cancer: A Prospective Study
Authors: Zu Ke , Martin Neil E. , Fiorentino Michelangelo , Flavin Richard , Lis Rosina T. , Sinnott Jennifer A. , Finn Stephen , Penney Kathryn L. , Ma Jing , Fazli Ladan , Gleave Martin E. , Bismar Tarek A. , Stampfer Meir J. , Pollak Michael N. , Loda Massimo , Mucci Lorelei A. , Giovannucci Edward 
Published: August 2013

Abstract
Background: Loss of PTEN has been shown to be associated with aggressive behavior of prostate cancer. It is less clear that loss of PTEN also increases the risk of cancer mortality. We investigated the association between PTEN expression and prostate cancer mortality and the potential effect modification by IGF-IR, a direct activator of the phosphoinositide-3-kinase (PI3K) pathway.
Methods: Protein expression in tumor was evaluated using tumor tissues obtained from 805 participants of the Physicians' Health and the Health Professionals Follow-up studies who were diagnosed with prostate cancer and underwent radical prostatectomy. Proportional hazard models were used to assess PTEN expression and its interaction with IGF-IR, in relation to lethal prostate cancer (cancer-specific death or distant metastases).
Results: Low PTEN expression was associated with an increased risk of lethal prostate cancer [HR, 1.7; 95% confidence interval (CI), 0.98–3.2; Ptrend = 0.04]. The association was attenuated after adjustment for Gleason grade, tumor stage, and prostate-specific antigen (PSA) at diagnosis. A significant negative interaction between PTEN and IGF-IR was found (Pinteraction = 0.03). Either reduction in PTEN or increase in IGF-IR expression was sufficient to worsen prognosis. Models including PTEN and IGF-IR expression offer additional predicting power to prostate cancer survival, compared to those only including demographic and clinical factors.
Conclusions: Low PTEN protein expression significantly increases the risk of lethal prostate cancer, particularly when the IGF-IR expression remains at normal level.
Impact: PTEN and IGF-IR expression in tumor are promising candidates for independent prognostic factors to predict lethal prostate cancer. Cancer Epidemiol Biomarkers Prev; 22(11); 1984–93. ©2013 AACR.
Associations between Dietary Acrylamide Intake and Plasma Sex Hormone Levels
Authors: Hogervorst Janneke G. , Fortner Renee T. , Mucci Lorelei A. , Tworoger Shelley S. , Eliassen A. Heather , Hankinson Susan E. , Wilson Kathryn M. 
Published: August 2013

AbstractBackground: The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiologic studies have observed positive associations between acrylamide intake and endometrial, ovarian, and breast cancer risks, which suggest that acrylamide may have sex-hormonal effects.Methods: We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and sex hormone–binding globulin (SHBG) among 687 postmenopausal and 1,300 premenopausal controls from nested case–control studies within the Nurses' Health Studies.Results: There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin, or SHBG. Among normal-weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, whereas statistically significant positive associations for testosterone and androstenedione were observed among overweight women.Conclusions: Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biologic plausibility to the observed increased risks of endometrial, ovarian, and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers.Impact: The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. Cancer Epidemiol Biomarkers Prev; 22(11); 2024–36. ©2013 AACR.
Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803
Authors: Warren Robert S. , Atreya Chloe E. , Niedzwiecki Donna , Weinberg Vivian K. , Donner David B. , Mayer Robert J. , Goldberg Richard M. , Compton Carolyn C. , Zuraek Marlene B. , Ye Cynthia , Saltz Leonard B. , Bertagnolli Monica M. 
Published: August 2013

Abstract
Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer.
Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL).
Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men.
Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men. Clin Cancer Res; 19(20); 5777–87. ©2013 AACR.
The Twist Box Domain Is Required for Twist1-induced Prostate Cancer Metastasis
Authors: Gajula Rajendra P. , Chettiar Sivarajan T. , Williams Russell D. , Thiyagarajan Saravanan , Kato Yoshinori , Aziz Khaled , Wang Ruoqi , Gandhi Nishant , Wild Aaron T. , Vesuna Farhad , Ma Jinfang , Salih Tarek , Cades Jessica , Fertig Elana , Biswal Shyam , Burns Timothy F. , Chung Christine H. , Rudin Charles M. , Herman Joseph M. , Hales Russell K. , Raman Venu , An Steven S. , Tran Phuoc T. 
Published: August 2013

Abstract
Twist1, a basic helix-loop-helix transcription factor, plays a key role during development and is a master regulator of the epithelial–mesenchymal transition (EMT) that promotes cancer metastasis. Structure–function relationships of Twist1 to cancer-related phenotypes are underappreciated, so we studied the requirement of the conserved Twist box domain for metastatic phenotypes in prostate cancer. Evidence suggests that Twist1 is overexpressed in clinical specimens and correlated with aggressive/metastatic disease. Therefore, we examined a transactivation mutant, Twist1-F191G, in prostate cancer cells using in vitro assays, which mimic various stages of metastasis. Twist1 overexpression led to elevated cytoskeletal stiffness and cell traction forces at the migratory edge of cells based on biophysical single-cell measurements. Twist1 conferred additional cellular properties associated with cancer cell metastasis including increased migration, invasion, anoikis resistance, and anchorage-independent growth. The Twist box mutant was defective for these Twist1 phenotypes in vitro. Importantly, we observed a high frequency of Twist1-induced metastatic lung tumors and extrathoracic metastases in vivo using the experimental lung metastasis assay. The Twist box was required for prostate cancer cells to colonize metastatic lung lesions and extrathoracic metastases. Comparative genomic profiling revealed transcriptional programs directed by the Twist box that were associated with cancer progression, such as Hoxa9. Mechanistically, Twist1 bound to the Hoxa9 promoter and positively regulated Hoxa9 expression in prostate cancer cells. Finally, Hoxa9 was important for Twist1-induced cellular phenotypes associated with metastasis. These data suggest that the Twist box domain is required for Twist1 transcriptional programs and prostate cancer metastasis.
Implications: Targeting the Twist box domain of Twist1 may effectively limit prostate cancer metastatic potential. Mol Cancer Res; 11(11); 1387–400. ©2013 AACR.
Inositol 1, 4, 5-Trisphosphate Receptors and Human Left Ventricular Myocytes
Authors: Signore Sergio , Sorrentino Andrea , Ferreira-Martins João , Kannappan Ramaswamy , Shafaie Mehrdad , Del Ben Fabio , Isobe Kazuya , Arranto Christian , Wybieralska Ewa , Webster Andrew , Sanada Fumihiro , Ogórek Barbara , Zheng Hanqiao , Liu Xiaoxia , del Monte Federica , D’Alessandro David A. , Wunimenghe Oriyanhan , Michler Robert E. , Hosoda Toru , Goichberg Polina , Leri Annarosa , Kajstura Jan , Anversa Piero , Rota Marcello 
Published: August 2013

Background—

Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca
2+
release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein–coupled receptor stimulation, affecting Ca
2+
cycling, enhancing myocyte performance, and potentially favoring an increase in the incidence of arrhythmias.

Methods and Results—

IP3R function was determined in human left ventricular myocytes, and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electric and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human left ventricular myocytes. After Gαq-protein–coupled receptor activation, Ca
2+
mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action potential, and occurrence of early afterdepolarizations. Ca
2+
transient amplitude and cell shortening are enhanced, and extrasystolic and dysregulated Ca
2+
elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that Gαq-protein–coupled receptor activation provides inotropic reserve, which is hampered by electric instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca
2+
load by IP3Rs promote Ca
2+
extrusion by forward-mode Na
+
/Ca
2+
exchange, an important mechanism of arrhythmic events.

Conclusions—
The Gαq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.
Negative Emotional Experiences during Navigation Enhance Parahippocampal Activity during Recall of Place Information
Authors: Chan Edgar , Baumann Oliver , Bellgrove Mark A. , Mattingley Jason B. 
Published: August 2013

Abstract
It is known that the parahippocampal cortex is involved in object–place associations in spatial learning, but it remains unknown whether activity within this region is modulated by affective signals during navigation. Here we used fMRI to measure the neural consequences of emotional experiences on place memory during navigation. A day before scanning, participants undertook an active object location memory task within a virtual house in which each room was associated with a different schedule of task-irrelevant emotional events. The events varied in valence (positive, negative, or neutral) and in their rate of occurrence (intermittent vs. constant). On a subsequent day, we measured neural activity while participants were shown static images of the previously learned virtual environment, now in the absence of any affective stimuli. Our results showed that parahippocampal activity was significantly enhanced bilaterally when participants viewed images of a room in which they had previously encountered negatively arousing events. We conclude that such automatic enhancement of place representations by aversive emotional events serves as an important adaptive mechanism for avoiding future threats.
Statistical Parameterization Expressing ENSO Variability and Reversibility in Response to CO2 Concentration Changes
Authors: Ohba Masamichi , Tsutsui Junichi , Nohara Daisuke 
Published: August 2013

Abstract
The degree of reversibility in the behavior of El Niño–Southern Oscillation (ENSO) in response to CO2 concentration changes is examined using the air–sea coupled Community Climate System Model, version 4. The model is run under simple and idealized climate change scenarios where atmospheric CO2 concentration is gradually increased to four times the preindustrial level and then gradually reduced at a similar rate along this trajectory. While the simulated ENSO amplitude is reduced when CO2 concentration increases, the amplitude is enhanced when CO2 decreases. This enhancement occurs with a relative El Niño–like warming of mean sea surface temperature. Most of the El Niño–like warming is attributed to a weakened cold water upwelling in the equatorial eastern Pacific. This weakened cooling is a result of a vertical ocean temperature gradient that is reduced in relation to a lag between subsurface temperature warming and surface temperature change. From these findings, a statistical parameterization expressing ENSO variability is developed in terms of the global-mean surface temperature and the vertical gradient of the global-mean temperature in the upper ocean. Plugging this parameterization into a statistical model of ENSO and combining the latter with a statistical spatial pattern of the ENSO-related temperature anomaly enables the reconstruction of surface temperature variability over North America. This approach can be useful when one assesses future climate changes under various CO2 emission scenarios using very simple models whose outputs are limited to a small number of global-mean variables.
Acceleration of the Antarctic Circumpolar Current by Wind Stress along the Coast of Antarctica
Authors: Zika Jan D. , Le Sommer Julien , Dufour Carolina O. , Naveira-Garabato Alberto , Blaker Adam 
Published: August 2013

Abstract
The influence of wind forcing on variability of the Antarctic Circumpolar Current (ACC) is investigated using a series of eddy-permitting ocean–sea ice models. At interannual and decadal time scales the ACC transport is sensitive to both the mean strength of westerly winds along the ACC circumpolar path, consistent with zonal momentum balance theories, and sensitive to the wind stresses along the coast of Antarctica, consistent with the “free mode” theory of Hughes et al. A linear combination of the two factors explains differences in ACC transport across 11 regional quasi-equilibrium experiments. Repeated single-year global experiments show that the ACC can be robustly accelerated by both processes. Across an ensemble of simulations with realistic forcing over the second half of the twentieth century, interannual ACC transport variability owing to the free-mode mechanism exceeds that due to the zonal momentum balance mechanism by a factor of between 3.5 and 5 to one. While the ACC transport may not accelerate significantly owing to projected increases in along-ACC winds in future decades, significant changes in transport could still occur because of changes in the stress along the coast of Antarctica.
Swallow Preservation Exercises during Chemoradiation Therapy Maintains Swallow Function
Authors: Duarte Victor M. , Chhetri Dinesh K. , Liu Yuan F. , Erman Andrew A. , Wang Marilene B. 
Published: August 2013

ObjectiveTo evaluate a swallow preservation protocol (SPP) in which patients received swallow therapy before, during, and after radiation treatment and its efficacy in maintaining swallowing function in head and neck cancer patients.DesignCase series with chart review.SettingTertiary care academic medical center.Subjects and MethodsEighty‐five patients who received radiation (RT) or chemoradiation (CRT) participated in the SPP from 2007 to 2012. Subjects were divided into 2 groups: compliant and noncompliant with SPP. At each SPP visit, the diet of each patient was recorded as regular (chewable), puree, liquid, or gastrostomy tube (G‐tube) dependent, along with their compliance with the swallow exercises. Patients were stratified by age, gender, tumor stage, type of treatment, radiation dose, diet change, dysguesia, odynophagia, pain, and stenosis. Statistical analysis was performed comparing the 2 compliance groups in regards to swallowing‐related outcomes at 1 month after completion of therapy.ResultsFifty‐seven patients were compliant and 28 were noncompliant with SPP during treatment. The compliant group had a higher percentage of patients tolerating a regular diet (54.4% vs 21.4%, P =. 008), a lower G‐tube dependence (22.8% vs 53.6%, P =. 008), and a higher rate of maintaining or improving their diet (54.4% vs 25.0%, P =. 025) compared to noncompliant patients.ConclusionA swallow preservation protocol appears to help maintain or improve swallow function in head and neck cancer patients undergoing RT or CRT. Patients who are able to comply with swallow exercises are less likely to worsen their diet, receive a G‐tube, or develop stenosis.
The development and evaluation of an educational intervention for primary care promoting person-centred responses to dementia
Authors: Edwards Rachel , Voss Sarah E , Iliffe Steve 
Published: August 2013

Background Early diagnosis of dementia within primary care is important to allow access to support. However, dementia remains under-detected in general practice. Aim This work aimed to develop and evaluate an educational intervention for primary care promoting person-centred responses to people experiencing cognitive decline. Method A prototype educational intervention was pilot tested and refined; the final version of the educational intervention was then evaluated in four volunteer practices. A questionnaire was administered pre- and post-training to 94 practice staff to assess knowledge and attitudes to dementia. The responses of general practitioners (who make diagnostic, referral and treatment decisions) were compared with those from other staff who do not have such roles. Findings Post-training, there were statistically significant improvements in understanding of person-centred care for people with dementia; attitudes to early diagnosis; awareness of non-cognitive dementia symptoms; and awareness of the role that non-clinical staff may have in recognising dementia. Conclusions A dementia education intervention for primary care which fosters person-centred attitudes can involve all members of a primary care team. Further research is needed to ascertain if improvements in knowledge and attitudes translate into improved practice.
Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin?
Authors: Kulozik Felix , Hasslacher Christoph 
Published: August 2013

Objectives: In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction. Methods: The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft–Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters. Results: The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR. Conclusions: Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is essential for the adjustment of insulin therapy in patients with diabetic nephropathy to achieve balanced glycemic control. To determine the underlying mechanisms, further studies on the pharmacokinetics and pharmacodynamics of the different insulins in patients with diabetic nephropathy are needed.
Polycomb repressive complex 2 (PRC2) suppresses Eμ-myc lymphoma
Authors: Lee Stanley C. W. , Phipson Belinda , Hyland Craig D. , Leong Huei San , Allan Rhys S. , Lun Aaron , Hilton Douglas J. , Nutt Stephen L. , Blewitt Marnie E. , Smyth Gordon K. , Alexander Warren S. , Majewski Ian J. 
Published: August 2013

Key Points
PRC1 and PRC2 have opposing activity in Eμ-myc lymphoma. Inhibition of PRC2 leads to increased self-renewal in B-cell progenitors.
Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality
Authors: Pidala Joseph , Wang Tao , Haagenson Michael , Spellman Stephen R. , Askar Medhat , Battiwalla Minoo , Baxter-Lowe Lee Ann , Bitan Menachem , Fernandez-Viña Marcelo , Gandhi Manish , Jakubowski Ann A. , Maiers Martin , Marino Susana R. , Marsh Steven G. E. , Oudshoorn Machteld , Palmer Jeanne , Prasad Vinod K. , Reddy Vijay , Ringden Olle , Saber Wael , Santarone Stella , Schultz Kirk R. , Setterholm Michelle , Trachtenberg Elizabeth , Turner E. Victoria , Woolfrey Ann E. , Lee Stephanie J. , Anasetti Claudio 
Published: August 2013

Key PointsAmino acid substitution at peptide-binding residues of the HLA class I molecule is associated with graft-versus-host disease and mortality. Avoidance of donor-recipient combinations that result in amino acid substitution at peptide-binding residues may improve transplant outcomes.