bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRE-HOSPITAL NON-INVASIVE VENTILATION FOR ACUTE RESPIRATORY FAILURE: A SYSTEMATIC REVIEW AND NETWORK META ANALYSIS
Authors: Goodacre Steve 
Published: August 2014

Objectives & BackgroundWe aimed to determine the effectiveness of pre-hospital continuous positive airway pressure (CPAP) or bi-level inspiratory positive airway pressure (BiPAP) compared with usual care for adults presenting to the emergency services with acute respiratory failure.MethodsWe searched 14 electronic databases and research registers from inception to August 2013. Searches were supplemented by hand-searching the reference list of relevant articles (including citation searching), the World Wide Web and contacting experts in the field. We selected randomised or quasi-randomised controlled trials that compared pre-hospital NIV to a relevant comparator treatment in patients with acute respiratory failure. An aggregate data network meta-analysis was used to jointly estimate intervention effects relative to standard care. A network meta-analysis using a mixture of individual patient-level data (IPD) and aggregate data was carried out to assess potential treatment effect modifiers.ResultsThe literature searches identified 2284 citations. Eight randomised and two quasi-randomised controlled trials (six CPAP; four BiPAP; sample sizes 23 to 207) were selected for inclusion. The aggregate data network meta-analysis suggested that CPAP was the most effective treatment in terms of mortality (probability=0.989) and intubation rate (probability=0.639), and reduced both mortality (odds ratio 0.41; 95% CrI (credible interval) 0.20 to 0.77) and intubation rate (0.32; 95% CrI 0.17 to 0.62) compared to standard care. The effect of BiPAP upon mortality (odds ratio 1.94; 95% CrI 0.65 to 6.14) and intubation rate (odds ratio 0.40; 95% CrI 0.14 to 1.16) was uncertain. The network meta-analysis using IPD and aggregate data suggested that sex was a modifier of the effect of treatment on mortality.ConclusionPre-hospital CPAP can reduce mortality and intubation rates compared to standard care, while the effectiveness of pre-hospital BiPAP is uncertain.Comparison of mortality for interventions versus standard care from the primary trials
Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR
Authors: Suwa Kenichiro , Satoh Hiroshi , Sano Makoto , Nobuhara Mamoru , Saitoh Takeji , Saotome Masao , Urushida Tsuyoshi , Katoh Hideki , Tawarahara Kei , Ohtani Hayato , Wakabayashi Yasushi , Takase Hiroyuki , Terada Hajime , Takehara Yasuo , Sakahara Harumi , Hayashi Hideharu 
Published: August 2014

ObjectiveThe prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury.MethodsStudy design: a multicentre trans-sectional study.Patients: 45 patients with APH and 5 with apical aneurysm diagnosed with transthoracic echocardiography (TTE) in the database of Hamamatsu Circulation Forum.Measure: the apical contraction with cine-cardiac MR (CMR), the myocardial fibrotic scar with late gadolinium enhancement (LGE)-CMR, and QRS fragmentation (fQRS) defined when two ECG-leads exhibited RSR’s patterns.ResultsCine-CMR revealed 27 patients with normal, 12 with hypokinetic and 11 with dyskinetic apical contraction. TTE misdiagnosed 11 (48%) patients with hypokinetic and dyskinetic contraction as those with normal contraction. Apical LGE was apparent in 10 (83%) and 11 (100%) patients with hypokinetic and dyskinetic contraction, whereas only in 11 patients (41%) with normal contraction (p<0.01). Patients with dyskinetic apical contraction had the lowest left ventricular ejection fraction, the highest prevalence of ventricular tachycardia, and the smallest ST depression and depth of negative T waves. The presence of fQRS was associated with impaired apical contraction and apical LGE (OR=8.32 and 8.61, p<0.05).ConclusionsCMR is superior to TTE for analysing abnormalities of the apex in patients with APH and with apical aneurysm. The presence of fQRS can be a promising parameter for the early detection of apical myocardial injury.
Age dating of an extensive thrust system on Mercury: implications for the planet's thermal evolution
Authors: Giacomini L. , Massironi M. , Marchi S. , Fassett C. I. , Di Achille G. , Cremonese G. 
Published: August 2014

Abstract
The tectonic evolution of Mercury is dominated at a global scale by contractional features such as lobate scarps that are widely distributed across the planet. These structures are thought to be the consequence of the secular cooling of Mercury. Therefore, dating these features is essential to place constraints on the timing of planetary cooling, which is important for understanding the thermal evolution of Mercury. In this work, we date an extended thrust system, which we term the Blossom Thrust System, located between 80°E and 100°E, and 30°N and 15°S, and which consists of several individual lobate scarps exhibiting a north–south orientation and a westward vergence. The age of the system was determined using several different methods. Traditional stratigraphic analysis was accompanied by crater counting of units that overlap the thrust system and by using the buffered crater-counting technique, allowing us to determine an absolute model age for the tectonic feature. These complementary methods give consistent results, implying that activity on the thrust ended between 3.5 and 3.7 Ga, depending on the adopted absolute-age model. These data provide an important insight into this portion of Mercury's crust, which may have implications for models of the thermal evolution of the planet as a whole.
Influence of deformation conditions on the development of heterogeneous recrystallization microstructures in experimentally deformed Carrara marble
Authors: Valcke S. L. A. , de Bresser J. H. P. , Pennock G. M. , Drury M. R. 
Published: August 2014

Abstract
Recrystallized grains are potentially useful as indicators of palaeostress in naturally deformed rocks, providing that well-calibrated relationships (palaeopiezometers) exist between the recrystallized grain size and stress. Rocks can exhibit microstructures that are heterogeneous, that is, containing recrystallized as well as deformed grains, and showing subgrains within grains that differ in size and character from the grain core to the mantle. Previous studies on palaeopiezometers only rarely took into account such heterogeneous microstructure. We used electron backscattered diffraction (EBSD) to accurately quantify the heterogeneous microstructures in experimentally deformed Carrara marble (flow stress 15–85 MPa, temperature 700–990 °C and natural strain 0.15–0.90). The sizes of bulges, recrystallized grains and deformed grains have been measured. We found that the overall character of the microstructures varies as a function of deformation conditions. In heterogeneous samples showing core-mantle microstructures, the sizes of the bulges and recrystallized grains are independent of strain and show an inverse dependency on stress. The recrystallized grains have been found to nucleate at grain boundary bulges. Our study illustrates that very different microstructures may develop in relation to the complexity of the recrystallization mechanisms. We therefore suggest that piezometers should be calibrated and applied for a single type of overall microstructure.
AEG-1 Regulates Retinoid X Receptor and Inhibits Retinoid Signaling
Authors: Srivastava Jyoti , Robertson Chadia L. , Rajasekaran Devaraja , Gredler Rachel , Siddiq Ayesha , Emdad Luni , Mukhopadhyay Nitai D. , Ghosh Shobha , Hylemon Phillip B. , Gil Gregorio , Shah Khalid , Bhere Deepak , Subler Mark A. , Windle Jolene J. , Fisher Paul B. , Sarkar Devanand 
Published: August 2014

Abstract
Retinoid X receptor (RXR) regulates key cellular responses such as cell growth and development, and this regulation is frequently perturbed in various malignancies, including hepatocellular carcinoma (HCC). However, the molecule(s) that physically govern this deregulation are mostly unknown. Here, we identified RXR as an interacting partner of astrocyte-elevated gene-1 (AEG-1)/metadherin (MTDH), an oncogene upregulated in all cancers. Upon interaction, AEG-1 profoundly inhibited RXR/retinoic acid receptor (RAR)–mediated transcriptional activation. Consequently, AEG-1 markedly protected HCC and acute myelogenous leukemia (AML) cells from retinoid- and rexinoid-induced cell death. In nontumorigenic cells and primary hepatocytes, AEG-1/RXR colocalizes in the nucleus in which AEG-1 interferes with recruitment of transcriptional coactivators to RXR, preventing transcription of target genes. In tumor cells and AEG-1 transgenic hepatocytes, overexpressed AEG-1 entraps RXR in cytoplasm, precluding its nuclear translocation. In addition, ERK, activated by AEG-1, phosphorylates RXR that leads to its functional inactivation and attenuation of ligand-dependent transactivation. In nude mice models, combination of all-trans retinoic acid (ATRA) and AEG-1 knockdown synergistically inhibited growth of human HCC xenografts. The present study establishes AEG-1 as a novel homeostatic regulator of RXR and RXR/RAR that might contribute to hepatocarcinogenesis. Targeting AEG-1 could sensitize patients with HCC and AML to retinoid- and rexinoid-based therapeutics. Cancer Res; 74(16); 4364–77. ©2014 AACR.
Sentinel Lymph Node Biopsy Revisited: Ultrasound-Guided Photoacoustic Detection of Micrometastases Using Molecularly Targeted Plasmonic Nanosensors
Authors: Luke Geoffrey P. , Myers Jeffrey N. , Emelianov Stanislav Y. , Sokolov Konstantin V. 
Published: August 2014

Abstract
Metastases rather than primary tumors are responsible for killing most patients with cancer. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure—sentinel LN biopsy—is generally used to identify metastatic cancer cells. Here, we introduce a new approach for more sensitive in vivo detection of LN micrometastases, based on the use of ultrasound-guided spectroscopic photoacoustic (sPA) imaging of molecularly activated plasmonic nanosensors (MAPS). Using a metastatic murine model of oral squamous cell carcinoma, we showed that MAPS targeted to the epidermal growth factor receptor shifted their optical absorption spectrum to the red-near-infrared region after specific interactions with nodal metastatic cells, enabling their noninvasive detection by sPA. Notably, LN metastases as small as 50 μm were detected at centimeter-depth range with high sensitivity and specificity. Large sPA signals appeared in metastatic LN within 30 minutes of MAPS injection, in support of the clinical utility of this method. Our findings offer a rapid and effective tool to noninvasively identify micrometastases as an alternate to sentinal node biopsy analysis. Cancer Res; 74(19); 5397–408. ©2014 AACR.
Abstract P1-03-02: “Normal” tissue adjacent to breast cancer is not normal
Authors: Clare SE , Pardo I , Mathieson T , Lillemoe HA , Blosser RJ , Choi M , Sauder CAM , Doxey DK , Badve S , Storniolo AMV , Atale R , Radovich M 
Published: August 2014

Abstract
Background: Gene expression data from pancreatic cancer, histologically normal tissue adjacent to the cancer and normal pancreas reveals that adjacent normal has already acquired a number of transcriptional alterations and is not, therefore, an appropriate baseline for comparison with cancers. (Gadaleta et al., 2011) The purpose of this study was to determine if this is also the case for breast cancer and, if so, to identify the differences in gene expression between adjacent normal and normal breast.
Methods: RNA-Seq data from breast cancer and adjacent normal was downloaded from the TCGA (The Cancer Genome Atlas) data portal. The epithelia from 20 frozen tissue cores from healthy premenopausal donors to the Susan G. Komen for the the Cure® Tissue Bank at the IU Simon Cancer Center were microdissected and the RNA isolated. RNA-seqeuncing was carried out using the Life Technologies SOLiD Platform. RPKM gene expression values from TCGA and sequencing of the Komen normal tissues were merged, quantile normalized, and batch effect corrected. Normalization and differential gene expression was performed using Partek Genomics Suite.
Results: Principal component analysis (PCA) reveals complete separation between adjacent normal and healthy normal breast tissue. Setting a maximum FDR (false discover rate) of 5%, 2239 genes are differentially expressed between adjacent normal and healthy normal. Ingenuity pathway analysis reveals that the Fos, Jun and TGFbeta pathways are active in the adjacent normal.
Conclusions: Tissue adjacent to a primary breast cancer is not normal when using healthy breast tissue as a comparator. As RNA-Seq data is digital, it is possible to quantify the changes in gene expression starting from healthy normal to normal adjacent to tumor to tumor. Increasing and decreasing gene expression values provide clues to the fundamental molecular changes occurring in histologically normal appearing adjacent tissue. The differences in gene expression we have identified are some of the earliest changes in breast carcinogenesis and provide insight into the etiology of this disease and, potentially, its prevention.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-03-02.
Abstract P1-05-24: Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis.
Authors: Borges S , Doppler H , Andorfer CA , Perez EA , Sun Z , Anastasiadis PZ , Thompson AE , Geiger XJ , Storz P 
Published: August 2014

Abstract
Epigenetic silencing of tumor suppressing genes by promoter-specific DNA methylation is common in many types of cancer. As an early event, this process has been well shown to promote tumor initiation and progression; however little is known how such epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes Protein Kinase D1 (PKD1), a serine/threonine kinase expressed in epithelial cells of the normal mammary gland that maintains the epithelial phenotype of normal breast cells and prevents epithelial-to-mesenchymal transition (EMT). PKD1 is also a critical suppressor of tumor cell invasion and is silenced in expression and activity during breast tumor progression. Here, we show that aberrant methylation of PRKD1 promoter region is not only correlated with the silencing of its expression but is also associated with invasiveness of breast cancer cell lines and with aggressiveness of breast tumors. Using the highly invasive MDA-MB-231 cells, we show that the inhibition of PRKD1 promoter methylation with the DNA methyltransferase inhibitor decitabine restores PKD1 expression and significantly decreases their invasive abilities in vitro. More importantly, in a tumor xenograft model it dramatically blocks tumor spread and metastasis to the lung in a PKD1-dependent fashion. Our data suggest that the status of epigenetic regulation of the PRKD1 promoter can provide valid information on the invasiveness of breast tumors, and therefore could serve as an early diagnostic marker. Moreover, targeted upregulation of PKD1 expression may be used as a therapeutic approach to reverse the invasive phenotype of breast cancer cells.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-24.
Abstract P4-14-07: Impact of preservation of the intercostobrachial nerve during axillary dissection on sensory change and health-related quality of life two years after breast cancer surgery
Authors: Taira N , Shimozuma K , Ohsumi S , Kuroi K , Shiroiwa T , Watanabe T , Saito M 
Published: August 2014

Abstract
Background: Sensory loss or paresthesia due to division of the intercostobrachial nerve (ICBN) is a complication of axillary lymph node dissection (ALND). Preservation of the ICBN may be of value, but few prospective studies have shown an impact of preservation on sensory changes or health related quality of life (HRQOL) after breast cancer surgery.
Methods: Prospective study was performed to evaluate the association of ICBN preservation with sensory change and HRQOL at 1 (baseline), 6, 12 and 24 months after breast cancer surgery in 140 patients. The sensory examination included dysesthesia, paresthesia, abnormal touch and pain sensation in the upper arm.
Results: Division of the ICBN did not influence the frequency or severity of subjective dysesthesia and paresthesia. There was no marked difference in touch or pain sensation at baseline between patients with a preserved (group P) and divided (group D) ICBN. In group P, the percentage of patients aware of a sensory deficit or loss decreased with time, and that of patients aware of a hypersensitive sensation increased. These changes did not occur in group D, leading to a significant difference between the groups at 24 months. The main difference between the groups was the area with reduced touch or pain sensation. This area decreased with time in group P, but not in group D. ICBN preservation or division did not influence HRQOL.
Conclusion: ICBN preservation in ALND has a benefit of a reduced area with long-term axillary hypoesthesia, but has no influence on improvement of pain and HRQOL.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-07.
Abstract P5-18-09: A Phase I Study of MM-302, a HER2-targeted Liposomal Doxorubicin, in Patients with Advanced, HER2- Positive Breast Cancer
Authors: Wickham T , Futch K 
Published: August 2014

Abstract
Background: Anthracyclines have been an effective backbone of breast cancer therapies for decades. However, cardiotoxicity issues associated with free anthracyclines have limited their effective use. While liposomal doxorubicin formulations have succeeded in reducing cardiotoxicity, they have failed to demonstrate clear-cut efficacy advantages. To address these safety and efficacy limitations, we have designed a pegylated liposomal doxorubicin formulation, MM-302, with anti-HER2 antibody fragments coupled to its surface. MM-302 specifically targets tumor cells overexpressing HER2 with minimal uptake into normal cells such as cardiomyocytes which express low levels of HER2. This first-in-human Phase 1 study evaluates the safety of MM-302 in patients with HER2+ advanced breast cancer (ABC).
Methods: Patients aged &gt; 18 years with histologically confirmed HER2+ advanced breast cancer that have progressed or recurred on standard therapy or for which no standard therapy exists who have adequate performance status, bone marrow reserve, and organ function, were eligible for the study. A standard 3 + 3 dose escalation design is used to determine the maximum tolerated dose (MTD) followed by expansion arms to evaluate activity. The primary endpoint is determination of the MTD. Secondary endpoints included determination of dose-limiting toxicity, adverse event(s), and pharmacokinetic and immunogenicity profiles of MM-302, as well as overall response and clinical benefit rates of MM-302. MM-302 is administered intravenously weekly in 4-week cycles.
Results: We report current findings containing data from four cohorts (8, 16, 30 and 40 mg/m2 Q4W). 14 patients have been enrolled in these cohorts; median age 55 (range 34–65), median cycles 2 (range 1–6). The most frequent AEs were constipation (53.8%), Fatigue (69.2%) and decreased appetite (46.2%). Five patients have achieved SD and one patient has achieved a PR. A pharmacokinetic analysis indicates a half-life of approximately 50 hours.
Conclusions: To date, results suggest that single agent MM-302 administered to patients with ABC is tolerable, without cardiotoxicity, in patients up to 40 mg/m2 Q4W. Updated data on additional dosing cohorts and expansion arms will be presented.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-09.
Abstract P5-20-04: Eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer: results from a phase 2, multicenter, single-arm study
Authors: Vahdat L , Schwartzberg L , Wilks S , Rege J , Liao J , Cox D , O'Shaughnessy J 
Published: August 2014

Abstract
Background: Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, has been approved for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. This study evaluates efficacy and safety of eribulin + trastuzumab (TRAZ) as first-line therapy for human epidermal growth factor receptor 2 positive (HER2+) locally recurrent or MBC.
Methods: Patients received eribulin mesylate at 1.4 mg/m2 IV on days 1, 8 and TRAZ initial dose of 8 mg/kg IV on day 1 every 21 days, followed by 6 mg/kg on day 1 of each subsequent cycle. For study inclusion, patients could have been previously treated with TRAZ, but at least 12 months should have passed since any prior neoadjuvant or adjuvant chemotherapy was used. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments are evaluated every 6 weeks for the first 6 cycles and every 6–12 weeks thereafter per RECIST 1.1.
Results: Updated results presented here as of June 1, 2012; 37 of 52 planned patients have been treated. Patient characteristics are as follows: median age: 58 years (range, 31–81), 70% have luminal subtype, 95% are stage IV disease, and 73% have visceral disease, 46% had prior neo/adjuvant, 22% had prior anthracycline and 32% had prior taxane, 35% had original diagnosis of MBC. Patients received median of 7 (1,20) cycles for eribulin and 9 (1,23) cycles for TRAZ. The most common treatment related AEs are reported in Table 1.

Treatment-related serious AEs were reported for 4 (11%) patients; neutropenia 3 (8%) and febrile neutropenia 2 (6%) patients each. Eight patients have discontinued treatment due to disease progression (PD). Best patient responses are found in Table 2.

Conclusions: Based on the updated preliminary results of this Phase II study, the combination of eribulin + trastuzumab as first-line therapy for HER2+ locally recurrent or MBC appears to demonstrate an acceptable safety profile with considerable tumor responses, including in patients with ER/PR+ disease. Accrual is ongoing and study completion is anticipated prior to SABCS 2012.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-04.