bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Imaging of Prostate Cancer Using [68Ga]-Labeled Bombesin Analog BAY86-7548
Authors: Kähkönen Esa , Jambor Ivan , Kemppainen Jukka , Lehtiö Kaisa , Grönroos Tove J. , Kuisma Anna , Luoto Pauliina , Sipilä Henri J. , Tolvanen Tuula , Alanen Kalle , Silén Jonna , Kallajoki Markku , Roivainen Anne , Schäfer Niklaus , Schibli Roger , Dragic Martina , Johayem Anass , Valencia Ray , Borkowski Sandra , Minn Heikki 
Published: August 2013

Abstract
Purpose: A novel [68Ga]-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 peptide (BAY86-7548) having high affinity to bombesin receptor subtype II to detect primary and metastatic prostate carcinoma using positron emission tomography/computed tomography (PET/CT) was synthesized and evaluated for prostate cancer.
Experimental Design: In this first human study with BAY86-7548, 14 men scheduled for radical prostatectomy (n = 11) or with biochemical recurrence after surgery or hormonal therapy (n = 3) were enrolled. The patients received an intravenous injection of BAY86-7548 followed by over 60-minute dynamic imaging of prostate gland (n = 10) and/or subsequent whole-body imaging (n = 14). The visual assessment of PET/CT images included evaluation of intraprostatic (12 subsextants) and pelvic nodal uptake of BAY86-7548 in 11 surgical patients and detection of potential metastatic foci in all patients. In patients with biochemical recurrence, results were compared with those of either [11C]-acetate (n = 2) or [18F]-fluoromethylcholine (n = 1) PET/CT.
Results: We found a sensitivity, specificity, and accuracy of 88%, 81% and 83%, respectively, for detection of primary PCa and sensitivity of 70% for metastatic lymph nodes using histology as gold standard. BAY86-7548 correctly detected local recurrence in prostate bed and showed nodal relapse in accordance with [11C]-acetate PET/CT in 2 patients with biochemical relapse. In the third hormone refractory patient, BAY86-7548 failed to show multiple bone metastases evident on [18F]-fluoromethylcholine PET/CT.
Conclusion: BAY86-7548 PET/CT is a promising molecular imaging technique for detecting intraprostatic prostate cancer. Clin Cancer Res; 19(19); 5434–43. ©2013 AACR.
Ponatinib—A Step Forward in Overcoming Resistance in Chronic Myeloid Leukemia
Authors: Frankfurt Olga , Licht Jonathan D. 
Published: August 2013

Abstract
With the current therapy, the improvement in survival of patient with early chronic phase chronic myelogenous leukemia (CML) is unrivaled by that of any other leukemia. In fact, extrapolation of the survival curves may suggest that life expectancy of patients who achieve and maintain predetermined milestones may not differ from that of the age-matched healthy adults. The main reasons for such success are the presence of a well-defined molecular target, the BCR-ABL oncogene, necessary and sufficient for the initiation and propagation of CML, and the powerful and selective agents that inhibit it. Five U.S. Food and Drug Administration (FDA)-approved tyrosine kinase inhibitors (TKI), each with unique activities and toxicity profiles, allow for individualized patient care. Despite the remarkable responses of most patients, a small but significant fraction of patients develops clinical resistance to the TKIs, some of which is attributed to the BCR-ABL kinase domain mutations affecting TKI binding and activity. The recently approved third-generation TKI ponatinib showed remarkable activity in the patients with multi-TKI–resistant disease. Particularly impressive was its efficacy in patients with T315I mutation that is resistant to all other TKIs. In lieu of the current emphasis on achieving earlier and more profound responses and excellent activity of ponatinib in the refractory setting, its optimal position among the available armamentarium of agents is being established. Clin Cancer Res; 19(21); 5828–34. ©2013 AACR.
Predicting Response to Bevacizumab in Ovarian Cancer: A Panel of Potential Biomarkers Informing Treatment Selection
Authors: Collinson Fiona , Hutchinson Michelle , Craven Rachel A. , Cairns David A. , Zougman Alexandre , Wind Tobias C. , Gahir Narinder , Messenger Michael P. , Jackson Sharon , Thompson Douglas , Adusei Cybil , Ledermann Jonathan A. , Hall Geoffrey , Jayson Gordon C. , Selby Peter J. , Banks Rosamonde E. 
Published: August 2013

Abstract
Purpose: The aim of this study was to identify and validate novel predictive and/or prognostic serum proteomic biomarkers in patients with epithelial ovarian cancer (EOC) treated as part of the phase III international ICON7 clinical trial.
Experimental Design: ICON7 was a phase III international trial in EOC which showed a modest but statistically significant benefit in progression-free survival (PFS) with the addition of bevacizumab to standard chemotherapy. Serum samples from 10 patients who received bevacizumab (five responders and five nonresponders) were analyzed by mass spectrometry to identify candidate biomarkers. Initial validation and exploration by immunoassay was undertaken in an independent cohort of 92 patients, followed by a second independent cohort of 115 patients (taken from across both arms of the trial).
Results: Three candidate biomarkers were identified: mesothelin, fms-like tyrosine kinase-4 (FLT4), and α1-acid glycoprotein (AGP). Each showed evidence of independent prognostic potential when adjusting for high-risk status in initial (P &lt; 0.02) and combined (P &lt; 0.01) validation cohorts. In cohort I, individual biomarkers were not predictive of bevacizumab benefit; however, when combined with CA-125, a signature was developed that was predictive of bevacizumab response and discriminated benefit attributable to bevacizumab better than clinical characteristics. The signature showed weaker evidence of predictive ability in validation cohort II, but was still strongly predictive considering all samples (P = 0.001), with an improvement in median PFS of 5.5 months in signature-positive patients in the experimental arm compared with standard arm.
Conclusions: This study shows a discriminatory signature comprising mesothelin, FLT4, AGP, and CA-125 as potentially identifying those patients with EOC more likely to benefit from bevacizumab. These results require validation in further patient cohorts. Clin Cancer Res; 19(18); 5227–39. ©2013 AACR.
PI3K Stimulates DNA Synthesis and Cell-Cycle Progression via Its p55PIK Regulatory Subunit Interaction with PCNA
Authors: Wang Guihua , Cao Xiaonian , Lai Senyan , Luo Xuelai , Feng Yongdong , Xia Xianmin , Yen Paul M. , Gong Jianping , Hu Junbo 
Published: August 2013

Abstract
Previously, we have shown that p55PIK, an isoform of class IA phosphoinositide 3-kinase (PI3K), specifically interacts with important cell-cycle regulators, such as retinoblastoma (Rb), to promote cell-cycle progression. Here, we used the glutathione S-transferase pull-down assay to identify other p55PIK-interacting proteins besides Rb in a Rb-deficient cell line and found that p55PIK interacted with proliferation cell nuclear antigen (PCNA), which plays a key role in coordinating both initiation of the leading strand DNA replication and discontinuous lagging strand synthesis. Overexpression of p55PIK increased, and knockdown decreased, DNA synthesis and DNA replication by modulating the binding of DNA polymerase δ (Polδ) to PCNA. Moreover, a cell-permeable peptide containing the N-terminal–binding domain of p55PIK (TAT–N24) disrupted the p55PIK–PCNA interaction in cancer cells, and also inhibited the DNA synthesis and tumor growth in cell culture and in vivo. Altogether, our results show that the p55PIK–PCNA interaction is important in regulating DNA synthesis and contributes to tumorigenesis. Furthermore, the p55PIK–PCNA interaction provides a potential new target for anticancer drug development. Mol Cancer Ther; 12(10); 2100–9. ©2013 AACR.
Enhancement of Tumor-Reactive Cytotoxic CD4+ T-cell Responses after Ipilimumab Treatment in Four Advanced Melanoma Patients
Authors: Kitano Shigehisa , Tsuji Takemasa , Liu Caillian , Hirschhorn-Cymerman Daniel , Kyi Chrisann , Mu Zhenyu , Allison James P. , Gnjatic Sacha , Yuan Jianda D. , Wolchok Jedd D. 
Published: August 2013

AbstractCD4+ T cells provide help to enhance and sustain cytotoxic CD8+ T-cell responses. A direct lytic role for this cell population in mouse models further supports the use of tumor-reactive CD4+ T cells for cancer immunotherapy. CTLA-4 blockade has been shown to expand antigen-specific cytotoxic CD4+ T cells in mouse models. We took advantage of spontaneous immunity to the NY-ESO-1 cancer-testis antigen to investigate quantitative and qualitative changes in antigen-specific CD4+ T-cell responses after ipilimumab (anti-CTLA-4 monoclonal antibody) treatment in patients with advanced melanoma. Four patients with NY-ESO-1 seropositive melanoma were chosen upon the availability of suitable blood specimens for characterizing the functions of NY-ESO-1 antigen-specific CD4+ T-cell response by enzyme-linked immunospot (ELISPOT), intracellular cytokine staining (ICS), and cytotoxicity assays. Multiple NY-ESO-1 antigen-specific CD4+ T-cell responses with TH1 dominance were induced or enhanced after ipilimumab treatment in peripheral blood in all four patients. NY-ESO-1 antigen–specific CD4+ T-cell lines established from all four patients after ipilimumab treatment recognized naturally processed NY-ESO-1 protein in antigen-presenting cells, expressed master transcription factor Eomesodermin (Eomes), and secreted perforin and Granzyme B. Finally, we showed that these NY-ESO-1 antigen-specific CD4+ T-cell lines directly lysed autologous melanoma cell lines expressing NY-ESO-1 in an MHC class II restricted manner. Our results show that antigen-specific cytotoxic CD4+ T-cell responses are induced after ipilimumab therapy in human cancer patients. Ipilimumab may induce the expression of lytic granules on antigen-specific cytotoxic CD4+ T cells via Eomes, revealing a novel consequence of immunologic checkpoint blockade. Cancer Immunol Res; 1(4); 235–44. ©2013 AACR.
Is Greater Temperature Change Within a Day Associated With Increased Emergency Hospital Admissions for Heart Failure?
Authors: Qiu Hong , Tak-sun Yu Ignatius , Tse Lap Ah , Tian Linwei , Wang Xiaorong , Wong Tze Wai 
Published: August 2013

Background—
Although the seasonal variation and the effect of cold temperature on heart failure (HF) morbidity have been well documented, it is unknown whether the temperature variation within a day, that is, diurnal temperature range (DTR), is an independent risk factor for HF. We hypothesized that large DTR might be a source of additional environmental stress and, therefore, a risk factor for HF exacerbation. We aimed to test the association between DTR and HF hospitalization and to examine the effect modifiers, such as age, sex, and season.

Methods and Results—

We collected daily meteorologic data and emergency HF hospital admissions from 2000 to 2007 in Hong Kong. We used Poisson regression models to fit the relationship between daily DTR and emergency HF hospitalizations, after adjusting for the time trend, seasonality, mean temperature, humidity, and levels of outdoor air pollution. We confirmed the seasonal variation of HF with peak hospital admissions in winter in Hong Kong. The adverse effects of DTR on emergency HF admissions were observed on the current day and lasted for the following several days. Every 1°C increase of DTR at lag
0
corresponded to 0.86% (95% confidence interval, 0.31%–1.43%) increment of emergency hospital admissions for HF. DTR exhibited significantly greater effect in the cool season, and on female and elderly patients.

Conclusions—
Greater temperature change within a day was associated with increased emergency hospital admissions for HF. Health policymakers and hospitals may want to take into account the increased demand of specific facilities for susceptive population in winter with greater daily temperature variations.
Global Proteomics and Pathway Analysis of Pressure-Overload–Induced Heart Failure and Its Attenuation by Mitochondrial-Targeted Peptides
Authors: Dai Dao-Fu , Hsieh Edward J. , Chen Tony , Menendez Lorena G. , Basisty Nathan B. , Tsai Lauren , Beyer Richard P. , Crispin David A. , Shulman Nicholas J. , Szeto Hazel H. , Tian Rong , MacCoss Michael J. , Rabinovitch Peter S. 
Published: August 2013

Background—
We investigated the protective effects of mitochondrial-targeted antioxidant and protective peptides, Szeto-Schiller (SS) 31 and SS20, on cardiac function, proteomic remodeling, and signaling pathways.

Methods and Results—
We applied an improved label-free shotgun proteomics approach to evaluate the global proteomics changes in transverse aortic constriction (TAC)–induced heart failure and the associated signaling pathway changes using ingenuity pathway analysis. We found that 538 proteins significantly changed after TAC, which mapped to 53 pathways. The top pathways were in the categories of actin cytoskeleton, mitochondrial function, intermediate metabolism, glycolysis/gluconeogenesis, and citrate cycle. Concomitant treatment with SS31 ameliorated the congestive heart failure phenotypes and mitochondrial damage induced by TAC, in parallel with global attenuation of mitochondrial proteome changes, with an average of 84% protection of mitochondrial and 69% of nonmitochondrial protein changes. This included significant amelioration of all the ingenuity pathway analysis noted above. SS20 had only modest effects on heart failure and this tracked with only partial attenuation of global proteomics changes; furthermore, actin cytoskeleton pathways were significantly protected in SS20, whereas mitochondrial and metabolic pathways essentially were not.

Conclusions—
This study elucidates the signaling pathways significantly changed in pressure-overload–induced heart failure. The global attenuation of TAC-induced proteomic alterations by the mitochondrial-targeted peptide SS31 suggests that perturbed mitochondrial function may be an upstream signal to many of the pathway alterations in TAC and supports the potential clinical application of mitochondrial-targeted peptide drugs for the treatment heart failure.
Long-Term Effects of Secondary Prevention on Cognitive Function in Stroke Patients
Authors: Douiri Abdel , McKevitt Christopher , Emmett Eva S. , Rudd Anthony G. , Wolfe Charles D.A. 
Published: August 2013

Background—
Limited long-term follow-up data exist on the impact of appropriate secondary prevention therapies on cognitive function in patients after first-ever stroke. The aim of this study is to determine the effect of secondary prevention of vascular events on cognitive function after stroke.

Methods and Results—

Data were collected between 1995 and 2011 (n=4413) from the community-based South London Stroke Register covering an inner-city multiethnic source population of 271 817 inhabitants. Modified Poisson regression models were constructed to adjust for cognitive function status at 3 months, demographic and socioeconomic characteristics, case mix, stroke subtype, vascular risk factors, disability, and stroke recurrence. In patients with ischemic strokes without a history of atrial fibrillation (AF), there was a reduced risk of cognitive impairment associated with the use of different prevention treatments: (1) antihypertensives (relative risk, 0.7 [95% confidence interval, 0.57
–
0.82] for diuretics; relative risk, 0.8 [95% confidence interval, 0.64
–
0.98] for angiotensin-converting enzyme inhibitors; and relative risk, 0.7 [95% confidence interval, 0.55
–
0.81] for their combination), (2) a combination of aspirin and dipyridamole (relative risk, 0.8 [95% confidence interval, 0.68
–
1.01]), and (3) statin (relative risk, 0.9 [95% confidence interval, 0.76
–
1.06]) when clinically indicated. Protective effects against cognitive impairment were also observed in patients on the combination of antihypertensives, antithrombotic agents, and lipid-lowering drugs (relative risk, 0.55 [95% confidence interval, 0.40
–
0.77]). No significant associations were noted between poststroke cognitive impairment and antihypertensives among hemorrhagic stroke patients.

Conclusions—
Appropriate vascular risk management was associated with a long-term reduced risk of cognitive impairment. Focus on optimal preventive drug therapy of vascular risk factors and management should be supported.
Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding
Authors: Sarode Ravi , Milling Truman J. , Refaai Majed A. , Mangione Antoinette , Schneider Astrid , Durn Billie L. , Goldstein Joshua N. 
Published: August 2013

Background—
Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal.

Methods and Results—

In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8–20.0) for the 4F-PCC group and 3.60 (1.9–38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, –5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (
P
<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event.

Conclusions—
4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00708435.
Three-dimensional circular various weave patterns in woven preform structures
Authors: Bilisik Kadir , Karaduman Nesrin Sahbaz , Bilisik Nedim Erman , Bilisik Havva Esra 
Published: August 2013

The aim of this study was to develop three-dimensional (3D) fully interlaced representative circular woven preform structures and to understand the effects of weave pattern and number of layers on 3D circular woven structures. Various 3D circular woven preforms were developed. Data generated from these structures included yarn-to-yarn space, density, yarn angle, yarn length and crimp. It was shown that the weave patterns affected the 3D circular woven preform structures. The yarn-to-yarn spaces in the 3D fully interlaced circular structures were high compared to the traditional 3D orthogonal circular woven structures in fabric circumference (fabric outside surface) due to the interlacement of the yarn sets. The 3D plain, twill and satin structures resulted in axial angle (θ a) in fabric length; circumferential angle (θ c), and interlaced radial angle (θ ri) in fabric circumference and fabric diameter due to the axial-circumferential and axial-radial interlacements. The weave patterns slightly affected the yarn angles. On the other hand, it was observed that the number of layers considerably affected the radial arc length and the radial length in wall thickness in the 3D circular woven structure. The interlacement on 3D plain, twill and satin circular woven structures resulted in axial crimp, circumferential crimp and radial crimp. The crimps in the 3D fully interlaced circular woven structures slightly depended on the types of weave pattern and the number of layers.
Modelling uniformly porous facades to predict dwelling infiltration rates
Authors: Jones BM , Lowe RJ , Davies M , Chalabi Z , Das P , Ridley I 
Published: August 2013

It is important to limit dwelling infiltration to reduce energy demand and help meet national climate change commitments while concurrently providing sufficient ventilation to deliver adequate indoor air quality. DOMVENT3D is a model of infiltration and exfiltration that assumes a linear pressure distribution over any number of uniformly porous facades and integrates the airflow rate in the vertical plane to predict the theoretically correct airflow rate through them. DOMVENT3D is a new development of an existing two-dimensional model of infiltration that provides more opportunities for investigating a greater number of dwellings than was previously possible. Initial testing suggests that DOMVENT3D is mathematically robust and is suitable for modelling a wide variety of dwelling types and geometries to assist engineers and policy makers. Practical application: The modern building services engineer may be required to model airflow networks in a building to balance the conflicting needs of energy consumption reduction and occupant health. Limiting exfiltration is one method of reducing heat losses from a building and so there is a need to model it accurately. This article presents a new model of infiltration and exfiltration through a uniformly porous facade that can be incorporated within advanced complex airflow network tools or applied using a simple spreadsheet.
I’ve had a good life, what’s left is a bonus: Factor analysis of the Mental Adjustment to Cancer Scale in a palliative care population
Authors: Goodwin Laura , Price Annabel , Lee William , Rayner Lauren , Moorey Stirling , Monroe Barbara , Sykes Nigel , Hansford Penny , Higginson Irene J , Hotopf Matthew 
Published: August 2013

Background: The Mental Adjustment to Cancer Scale is an assessment tool commonly used to measure coping in cancer patients, which characterises adaptive coping under the label of ‘fighting spirit’. Aim: This study explores adaptation in patients with advanced cancer, by examining the factor structure of the Mental Adjustment to Cancer Scale. Further aims were to examine associations between types of coping and psychological outcomes measured at the same time (time 1) and 4 weeks after referral to palliative care services (time 2). Design: A cross-sectional study with a follow-up assessment 4 weeks later. Factor analysis examined the structure of the Mental Adjustment to Cancer Scale at time 1. Setting/participants: A total of 275 patients with advanced cancer receiving palliative care, of whom 193 took part at follow-up. Results: This study provided evidence for the internal consistency and validity of a new scale of ‘acceptance and positivity’ for use in advanced cancer patients. Patients with a desire for hastened death had lower acceptance and positivity, and patients with higher global quality of life reported a higher level. Social support was positively associated with acceptance and positivity. Higher scores on the acceptance and positivity scale were associated with reduced odds of a desire for hastened death at time 2. Conclusion: Adaptation to advanced cancer differs from adaptation to early stage cancer, comprising a general acceptance of the illness and trying to make the most of the time that is left. Individuals with low social support were less likely to evidence appropriate adaptation to their illness.