bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of compensatory processes of postnatal hypoxia in newborn piglets applying short-term nonlinear dynamics analysis
Authors: Schulz Steffen , Reulecke Sina , Eiselt Michael , Schwab Karin , Witte Herbert , Walter Bernd , Bauer Reinhard , Voss Andreas 
Published: October 2011

AbstractBackgroundNewborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adapting their vital functions. Exposure to hypoxia leads to an increase in the sympathetic tone causing cardio-respiratory response, peripheral vasoconstriction and vasodilatation in privileged organs like the heart and brain. However, there is only limited information available about the time and intensity changes of the underlying complex processes controlled by the autonomic nervous system.MethodsIn this study an animal model involving seven piglets was used to examine an induced state of circulatory redistribution caused by moderate oxygen deficit. In addition to the main focus on the complex dynamics occurring during sustained normocapnic hypoxia, the development of autonomic regulation after induced reoxygenation had been analysed. For this purpose, we first introduced a new algorithm to prove stationary conditions in short-term time series. Then we investigated a multitude of indices from heart rate and blood pressure variability and from bivariate interactions, also analysing respiration signals, to quantify the complexity of vegetative oscillations influenced by hypoxia.ResultsThe results demonstrated that normocapnic hypoxia causes an initial increase in cardiovascular complexity and variability, which decreases during moderate hypoxia lasting one hour (p < 0.004). After reoxygenation, cardiovascular complexity parameters returned to pre-hypoxic values (p < 0.003), however not respiratory-related complexity parameters.ConclusionsIn conclusion, indices from linear and nonlinear dynamics reflect considerable temporal changes of complexity in autonomous cardio-respiratory regulation due to normocapnic hypoxia shortly after birth. These findings might be suitable for non-invasive clinical monitoring of hypoxia-induced changes of autonomic regulation in newborn humans.
Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes
Authors: Rago Vittoria , Romeo Francesco , Giordano Francesca , Maggiolini Marcello , Carpino Amalia 
Published: October 2011

Abstract

Background
Estrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER) has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells.

Methods
This study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex-cord stromal and germ cell tumors) by immunohistochemical and Western Blot analyses.

Results
In control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results.

Conclusions
These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells.
Research advances on flotillins
Authors: Zhao Feng , Zhang Jie , Liu Yong-Sheng , Li Li , He Ya-Li 
Published: October 2011

Abstract
The proteins of flotillin-1 and flotillin-2 were originally discovered in axon regeneration of goldfish retinal ganglion cells. They are generally used as marker proteins of lipid rafts and considered to be scaffolding proteins of lipid microdomains. Although they are ubiquitously expressed and well-conserved from fly to man, their exact functions remain controversial. In this review, we summarize the structure of flotillins and some functions of them, such as regulating axon regeneration, endocytosis, T cell activation, insulin signaling, membrane protein recruitment, roles in the progression of some diseases and so on.
Autophagy Impairment in a Mouse Model of Neuropathic Pain
Authors: Berliocchi Laura , Russo Rossella , Maiarù Maria , Levato Alessandra , Bagetta Giacinto , Corasaniti Maria Tiziana 
Published: October 2011

Autophagy is an intracellular membrane trafficking pathway controlling the delivery of cytoplasmic material to the lysosomes for degradation. It plays an important role in cell homeostasis in both normal settings and abnormal, stressful conditions. It is now recognised that an imbalance in the autophagic process can impact basal cell functions and this has recently been implicated in several human diseases, including neurodegeneration and cancer. Here, we investigated the consequences of nerve injury on the autophagic process in a commonly used model of neuropathic pain. The expression and modulation of the main autophagic marker, the microtubule-associated protein 1 light chain 3 (LC3), was evaluated in the L4-L5 cord segment seven days after spinal nerve ligation (SNL). Levels of LC3-II, the autophagosome-associated LC3 form, were markedly higher in the spinal cord ipsilateral to the ligation side, appeared to correlate with the upregulation of the calcium channel subunit α2δ-1 and were not present in mice that underwent sham surgery. However, LC3-I and Beclin 1 expression were only slightly increased. On the contrary, SNL promoted the accumulation of the ubiquitin- and LC3-binding protein p62, which inversely correlates with autophagic activity, thus pointing to a block of autophagosome turnover. Our data showed for the first time that basal autophagy is disrupted in a model of neuropathic pain.
Total error shift patterns for daily CT on rails image-guided radiotherapy to the prostate bed
Authors: Cavalieri Ronaldo , Gay Hiram A , Liu Jingxia , Ferreira Maria C , Mota Helvecio C , Sibata Claudio H , Allison Ron R 
Published: October 2011

Abstract

Background
To evaluate the daily total error shift patterns on post-prostatectomy patients undergoing image guided radiotherapy (IGRT) with a diagnostic quality computer tomography (CT) on rails system.

Methods
A total of 17 consecutive post-prostatectomy patients receiving adjuvant or salvage IMRT using CT-on-rails IGRT were analyzed. The prostate bed's daily total error shifts were evaluated for a total of 661 CT scans.

Results
In the right-left, cranial-caudal, and posterior-anterior directions, 11.5%, 9.2%, and 6.5% of the 661 scans required no position adjustments; 75.3%, 66.1%, and 56.8% required a shift of 1 - 5 mm; 11.5%, 20.9%, and 31.2% required a shift of 6 - 10 mm; and 1.7%, 3.8%, and 5.5% required a shift of more than 10 mm, respectively. There was evidence of correlation between the x and y, x and z, and y and z axes in 3, 3, and 3 of 17 patients, respectively. Univariate (ANOVA) analysis showed that the total error pattern was random in the x, y, and z axis for 10, 5, and 2 of 17 patients, respectively, and systematic for the rest. Multivariate (MANOVA) analysis showed that the (x,y), (x,z), (y,z), and (x, y, z) total error pattern was random in 5, 1, 1, and 1 of 17 patients, respectively, and systematic for the rest.

Conclusions
The overall daily total error shift pattern for these 17 patients simulated with an empty bladder, and treated with CT on rails IGRT was predominantly systematic. Despite this, the temporal vector trends showed complex behaviors and unpredictable changes in magnitude and direction. These findings highlight the importance of using daily IGRT in post-prostatectomy patients.
DENSE: efficient and prior knowledge-driven discovery of phenotype-associated protein functional modules
Authors: Hendrix Willam , Rocha Andrea M , Padmanabhan Kanchana , Choudhary Alok , Scott Kathleen , Mihelcic James R , Samatova Nagiza F 
Published: October 2011

AbstractBackgroundIdentifying cellular subsystems that are involved in the expression of a target phenotype has been a very active research area for the past several years. In this paper,cellular subsystemrefers to a group of genes (or proteins) that interact and carry out a common function in the cell. Most studies identify genes associated with a phenotype on the basis of some statistical bias, others have extended these statistical methods to analyze functional modules and biological pathways for phenotype-relatedness. However, a biologist might often have a specific question in mind while performing such analysis and most of the resulting subsystems obtained by the existing methods might be largely irrelevant to the question in hand. Arguably, it would be valuable to incorporate biologist's knowledge about the phenotype into the algorithm. This way, it is anticipated that the resulting subsytems would not only be related to the target phenotype but also contain information that the biologist is likely to be interested in.ResultsIn this paper we introduce a fast and theoretically guranteed method calledDENSE(Dense and ENriched Subgraph Enumeration) that can take in as input a biologist'spriorknowledge as a set of query proteins and identify all the dense functional modules in a biological network that contain some part of the query vertices. The density (in terms of the number of network egdes) and the enrichment (the number of query proteins in the resulting functional module) can be manipulated via two parameters γ andμ, respectively.ConclusionThis algorithm has been applied to the protein functional association network ofClostridium acetobutylicumATCC 824, a hydrogen producing, acid-tolerant organism. The algorithm was able to verify relationships known to exist in literature and also some previously unknown relationships including those with regulatory and signaling functions. Additionally, we were also able to hypothesize that some uncharacterized proteins are likely associated with the target phenotype. The DENSE code can be downloaded fromhttp://www.freescience.org/cs/DENSE/
Loop-mediated isothermal amplification: rapid detection of Angiostrongylus cantonensis infection in Pomacea canaliculata
Authors: Chen Rui , Tong QunBo , Zhang Yi , Lou Di , Kong QingMing , Lv Shan , Zhuo MingMing , Wen LiYong , Lu ShaoHong 
Published: October 2011

Abstract

Background

Angiostrongylus cantonensis is a zoonotic parasite that causes eosinophilic meningitis in humans. The most common source of infection with A. cantonensis is the consumption of raw or undercooked mollusks (e.g., snails and slugs) harbouring infectious third-stage larvae (L3). However, the parasite is difficult to identify in snails. The purpose of this study was to develop a quick, simple molecular method to survey for A. cantonensis in intermediate host snails.

Findings
We used a loop-mediated isothermal amplification (LAMP) assay, which was performed using Bst DNA polymerase. Reactions amplified the A. cantonensis 18S rRNA gene and demonstrated high sensitivity; as little as 1 fg of DNA was detected in the samples. Furthermore, no cross-reactivity was found with other parasites such as Toxoplasma gondii, Plasmodium falciparum, Schistosoma japonicum, Clonorchis sinensis, Paragonimus westermani and Anisakis. Pomacea canaliculata snails were exposed to A. cantonensis first-stage larvae (L1) in the laboratory, and L3 were observed in the snails thirty-five days after infection. All nine samples were positive as determined by the LAMP assay for A. cantonensis, which was identified as positive by using PCR and microscopy, this demonstrates that LAMP is sensitive and effective for diagnosis.

Conclusions
LAMP is an appropriate diagnostic method for the routine identification of A. cantonensis within its intermediate host snail P. canaliculata because of its simplicity, sensitivity, and specificity. It holds great promise as a useful monitoring tool for A. cantonensis in endemic regions.
Eight-Signature Classifier for Prediction of Nasopharyngeal Carcinoma Survival
Authors: Wang Hai-Yun , Sun Bing-Yu , Zhu Zhi-Hua , Chang Ellen T. , To Ka-Fai , Hwang Jacqueline S.G. , Jiang Hao , Kam Michael Koon-Ming , Chen Gang , Cheah Shie-Lee , Lee Ming , Liu Zhi-Wei , Chen Jing , Zhang Jia-Xing , Zhang Hui-Zhong , He Jie-Hua , Chen Fa-Long , Zhu Xiao-Dong , Huang Ma-Yan , Liao Ding-Zhun , Fu Jia , Shao Qiong , Cai Man-Bo , Du Zi-Ming , Yan Li-Xu , Hu Chun-Fang , Ng Ho-Keung , Wee Joseph T.S. , Qian Chao-Nan , Liu Qing , Ernberg Ingemar , Ye Weimin , Adami Hans-Olov , Chan Anthony T. , Zeng Yi-Xin , Shao Jian-Yong 
Published: October 2011

Purpose Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC. Patients and Methods We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM) –based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients. Results The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort. Conclusion As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.
Evidence for Sequenced Molecular Evolution of IDH1 Mutant Glioblastoma From a Distinct Cell of Origin
Authors: Lai Albert , Kharbanda Samir , Pope Whitney B. , Tran Anh , Solis Orestes E. , Peale Franklin , Forrest William F. , Pujara Kanan , Carrillo Jose A. , Pandita Ajay , Ellingson Benjamin M. , Bowers Chauncey W. , Soriano Robert H. , Schmidt Nils O. , Mohan Sankar , Yong William H. , Seshagiri Somasekar , Modrusan Zora , Jiang Zhaoshi , Aldape Kenneth D. , Mischel Paul S. , Liau Linda M. , Escovedo Cameron J. , Chen Weidong , Nghiemphu Phioanh Leia , James C. David , Prados Michael D. , Westphal Manfred , Lamszus Katrin , Cloughesy Timothy , Phillips Heidi S. 
Published: October 2011

Purpose Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1R132MUT) is frequent in low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, regardless of clinical history. To determine how GBMs arising with IDH1R132MUT differ from other GBMs, we undertook a comprehensive comparison of patients presenting clinically with primary GBM as a function of IDH1R132 mutation status. Patients and Methods In all, 618 treatment-naive primary GBMs and 235 lower-grade diffuse gliomas were sequenced for IDH1R132 and analyzed for demographic, radiographic, anatomic, histologic, genomic, epigenetic, and transcriptional characteristics. Results Investigation revealed a constellation of features that distinguishes IDH1R132MUT GBMs from other GBMs (including frontal location and lesser extent of contrast enhancement and necrosis), relates them to lower-grade IDH1R132MUT gliomas, and supports the concept that IDH1R132MUT gliomas arise from a neural precursor population that is spatially and temporally restricted in the brain. The observed patterns of DNA sequence, methylation, and copy number alterations support a model of ordered molecular evolution of IDH1R132MUT GBM in which the appearance of mutant IDH1 protein is an initial event, followed by production of p53 mutant protein, and finally by copy number alterations of PTEN and EGFR. Conclusion Although histologically similar, GBMs arising with and without IDH1R132MUT appear to represent distinct disease entities that arise from separate cell types of origin as the result of largely nonoverlapping sets of molecular events. Optimal clinical management should account for the distinction between these GBM disease subtypes.
Capecitabine Versus Classical Cyclophosphamide, Methotrexate, and Fluorouracil As First-Line Chemotherapy for Advanced Breast Cancer
Authors: Stockler Martin R. , Harvey Vernon J. , Francis Prudence A. , Byrne Michael J. , Ackland Stephen P. , Fitzharris Bernie , Van Hazel Guy , Wilcken Nicholas R.C. , Grimison Peter S. , Nowak Anna K. , Gainford M. Corona , Fong Akiko , Paksec Lisa , Sourjina Tatiana , Zannino Diana , Gebski Val , Simes R. John , Forbes John F. , Coates Alan S. 
Published: October 2011

Purpose We compared oral capecitabine, administered intermittently or continuously, versus classical cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for women with advanced breast cancer unsuited to more intensive regimens. Patients and Methods Three hundred twenty-three eligible women were randomly assigned to capecitabine administered intermittently (1,000 mg/m2 twice daily for 14 of every 21 days; n = 107) or continuously (650 mg/m2 twice daily for 21 of every 21 days; n = 107), or to classical CMF (oral cyclophosphamide 100 mg/m2 days 1 to 14 with intravenous methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 on days 1 and 8 every 28 days; n = 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P > .05), combined for definitive comparisons versus CMF. Results Quality-adjusted PFS (P = .2), objective tumor response rate (20%; P = .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P = .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P = .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine. Conclusion Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.
Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial
Authors: Wells Samuel A. , Robinson Bruce G. , Gagel Robert F. , Dralle Henning , Fagin James A. , Santoro Massimo , Baudin Eric , Elisei Rossella , Jarzab Barbara , Vasselli James R. , Read Jessica , Langmuir Peter , Ryan Anderson J. , Schlumberger Martin J. 
Published: October 2011

Purpose There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients and Methods Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Results Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Conclusion Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).
First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors
Authors: Yap Timothy A. , Yan Li , Patnaik Amita , Fearen Ivy , Olmos David , Papadopoulos Kyriakos , Baird Richard D. , Delgado Liliana , Taylor Adekemi , Lupinacci Lisa , Riisnaes Ruth , Pope Lorna L. , Heaton Simon P. , Thomas George , Garrett Michelle D. , Sullivan Daniel M. , de Bono Johann S. , Tolcher Anthony W. 
Published: October 2011

PurposeAKT signaling is frequently deregulated in human cancers. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity in preclinical models. A phase I study of MK-2206 was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor efficacy.Patients and MethodsPatients with advanced solid tumors received MK-2206 on alternate days. Paired tumor biopsies were mandated at the MTD for biomarker studies. PD studies incorporated tumor and hair follicle analyses, and putative predictive biomarker studies included tumor somatic mutation analyses and immunohistochemistry for phosphatase and tensin homolog (PTEN) loss.ResultsThirty-three patients received MK-2206 at 30, 60, 75, or 90 mg on alternate days. Dose-limiting toxicities included skin rash and stomatitis, establishing the MTD at 60 mg. Drug-related toxicities included skin rash (51.5%), nausea (36.4%), pruritus (24.2%), hyperglycemia (21.2%), and diarrhea (21.2%). PKs (area under the concentration-time curve from 0 to 48 hours and maximum measured plasma concentration) were dose proportional. Phosphorylated serine 473 AKT declined in all tumor biopsies assessed (P = .015), and phosphorylated threonine 246 proline-rich AKT substrate 40 was suppressed in hair follicles at 6 hours (P = .008), on days 7 (P = .028) and 15 (P = .025) with MK-2206; reversible hyperglycemia and increases in insulin c-peptide were also observed, confirming target modulation. A patient with pancreatic adenocarcinoma (PTEN loss; KRAS G12D mutation) treated at 60 mg on alternate days experienced a decrease of approximately 60% in cancer antigen 19-9 levels and 23% shrinkage in tumor measurements. Two patients with pancreatic neuroendocrine tumors had minor tumor responses.ConclusionMK-2206 was well tolerated, with evidence of AKT signaling blockade. Rational combination trials are ongoing to maximize clinical benefit with this therapeutic strategy.