bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Gene RNF138 Expressed in Human Gliomas and Its Function in the Glioma Cell Line U251
Authors: Zhou You-xin , Chen San-song , Wu Ting-feng , Ding Da-dong , Chen Xiong-hui , Chen Jin-ming , Su Zuo-peng , Li Bin , Chen Gui-lin , Xie Xue-shun , Dai Yan-fang , Wei Yong-xin , Du Zi-wei 
Published: January 2015

Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes and the inactivation of tumor suppressor genes. Whether the RING finger protein, RNF138, a newly discovered protein, plays a role in glioma oncogenesis is unknown. The present study investigates the expression levels of RNF138 mRNA in glioma samples and noncancerous brain samples and its function in the human glioma cell line U251.Methods: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of 35 pathological confirmed glioma samples (Grade I – 4 cases, Grade II – 13 cases, Grade III – 11 cases, and Grade IV – 7 cases) and five noncancerous brain tissue samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi) with the lentivirus vector system, the expression of RNF138 was inhibited in the human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138-knockdown on cell proliferation were assessed by Cellomics, and cell cycle and cell apoptosis were assessed by FACS.Results: The RNF138 mRNA is expressed in the five glioma cell lines, and its expression level is significantly higher in glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138 expression, U251 cell proliferation was inhibited and cell apoptosis increased. At the same time, S stage cells lessened and G2 stage cells increased.Conclusion: The RNF138 gene is highly expressed in glioma tissue and glioma cell lines. It plays an important role in glioma cell proliferation, apoptosis, and cell cycle.
A Role of Three-Dimensional (3D)-Reconstruction in the Classification of Lung Adenocarcinoma
Authors: Onozato Maristela L. , Klepeis Veronica E. , Yagi Yukako , Mino-Kenudson Mari 
Published: January 2015

Background: Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas and different fields of view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, the most frequent histology type of lung cancer characterized by its morphological heterogeneity.Objective: In this work, we tested whether an automated tissue sectioning machine and slide scanning system could generate precise 3D-reconstruction of microanatomy of the lung and help us better understand and define histologic subtypes of lung adenocarcinoma.Methods: Four formalin-fixed human lung adenocarcinoma resections were studied. Paraffin embedded tissues were sectioned with Kurabo-Automated tissue sectioning machine and serial sections were automatically stained and scanned with a Whole Slide Imaging system. The resulting stacks of images were 3D reconstructed by Pannoramic Viewer software.Results: Two of the four specimens contained islands of tumor cells detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications. 3D-reconstruction revealed the details of spatial distribution and structural interaction of the tumor that could hardly be observed by 2D light microscopy studies. The islands of tumor cells extended into a deeper aspect of the tissue, and were interconnected with each other and with the main tumor with a solid pattern that was surrounded by the islands. The finding raises the question whether the islands of tumor cells should be classified into a solid pattern in the current classification.Conclusion: The combination of new technologies enabled us to build an effective 3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us refine the classification of lung adenocarcinoma by adding detailed spatial/structural information to 2D light microscopy evaluation.
Study on Interaction of Cationic Porphyrazine with Synthetic Polynucleotides
Authors: Dezhampanah Hamid , Fyzolahjani Soghra 
Published: January 2015

Interactions of cationic tetrakis (N, N′, N″, N‴- tetramethyltetra-3, 4-pyridinoporphyrazinatozinc (II) (Zn (tmtppa)) with synthetic polynucleotides, poly (G-C) and poly (A-T), and calf thymus DNA have been characterized in 7.5 mM phosphate buffer of pH 7.2 by UV-Vis absorption and fluorescence spectroscopy. The appearance of hypochromicity more than 30% in UV-Vis spectra of porphyrazine due to interaction of both poly (G-C) and poly (A-T) indicates interaction similar to that of porphyrazine with DNA.The binding constants were determined from the changes in the Q-band maximum of the porphyrazine spectra at various poly (G-C) and DNA concentrations. The values of K were 2.5 × 106M−1, 2.5 × 106M−1and 2.5 × 105M−1for poly (G-C), poly (A-T) and DNA, respectively, at 25°C. The thermodynamic parameters (ΔG°, ΔH°, ΔS°) were calculated using the van't Hoff equation at various temperatures. The enthalpy and entropy changes were determined to be 41.14 kJ mol−1and 260.50 J mol−1·K−1for poly (G-C) and 53.59 kJ mol−1and 285.46 J mol−1·K−1for DNA at 25°C. The positive and large values of the entropy and enthalpy suggest that both hydrophobic and electrostatic interactions may play an important role in the stabilization of the complex formation. The binding of polynucleotides to porphyrazine quenches fluorescence emission of ethidium bromide (EB), and the quenching process obeys linear Stern-Volmer relationship. The results reviled groove-binding mode of porphyrazine for both AT- and GC-rich polynucleotides of DNA.
Spectroscopic Studies on the Interaction of a Water-Soluble Cationic Porphyrin with Bovine Serum Albumin
Authors: Dezhampanah Hamid , Bordbar Abdol-Khalegh , Khodadusdt Yadolahe 
Published: January 2015

The interaction of a water-soluble cationic porphyrin, Cobalt(III) 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin [Co(III)TMPyP], with bovine serum albumin (BSA) has been studied in 1 mM phosphate buffer pH 7.0 containing 5 mM NaCl by UV-vis absorption, resonance light scattering (RLS) and fluorescence spectroscopies at 25°C. The results of RLS studies represent no aggregate formation of porphyrin in the surface of BSA and low tendency of this porphyrin for aggregate formation.The binding of porphyrin complex to BSA quenches fluorescence emission of BSA via a dynamic mechanism and the quenching process obeys a linear Stern-Volmer relationship. The values of Stern-Volmer constants, KSV, was determined nearly 105M−1, that depend on BSA concentration. The average aggregation number of BSA calculated from the analysis of fluorescence quenching data indicates that absence of any porphyrin induced aggregation of BSA due to its interaction with porphyrin complex. The binding of Co(III) TMPyP had no obvious effect on the molecular conformation of the protein. Electrostatic force played an important role in the binding due to the opposite charges on porphyrin and the protein.
Interferon Regulatory Factor-1 Signaling Regulates the Switch between Autophagy and Apoptosis to Determine Breast Cancer Cell Fate
Authors: Schwartz-Roberts Jessica L. , Cook Katherine L. , Chen Chun , Shajahan-Haq Ayesha N. , Axelrod Margaret , Wärri Anni , Riggins Rebecca B. , Jin Lu , Haddad Bassem R. , Kallakury Bhaskar V. , Baumann William T. , Clarke Robert 
Published: January 2015

Abstract
Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell fate in several cell types. Here, we report an inverse correlation in expression of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells that directly affects their cell fate. In mice harboring mutant Atg7, nuclear IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic investigations identified ATG7 and the cell death modulator beclin-1 (BECN1) as negative regulators of IRF1. Silencing ATG7 or BECN1 caused estrogen receptor-α to exit the nucleus at the time when IRF1 nuclear localization occurred. Conversely, silencing IRF1 promoted autophagy by increasing BECN1 and blunting IGF1 receptor and mTOR survival signaling. Loss of IRF1 promoted resistance to antiestrogens, whereas combined silencing of ATG7 and IRF1 restored sensitivity to these agents. Using a mathematical model to prompt signaling hypotheses, we developed evidence that ATG7 silencing could resensitize IRF1-attenuated cells to apoptosis through mechanisms that involve other estrogen-regulated genes. Overall, our work shows how inhibiting the autophagy proteins ATG7 and BECN1 can regulate IRF1-dependent and -independent signaling pathways in ways that engender a new therapeutic strategy to attack breast cancer. Cancer Res; 75(6); 1046–55. ©2015 AACR.
Redundancy: A Critical Obstacle to Improving Cancer Therapy
Authors: Lavi Orit 
Published: January 2015

Abstract
A system characterized by redundancy has various elements that are able to act in the same biologic or dynamic manner, where the inhibition of one of those elements has no significant effect on the global biologic outcome or on the system's dynamic behavior. Methods that aim to predict the effectiveness of cancer therapies must include evolutionary and dynamic features that would change the static view that is widely accepted. Here, we explore several important issues about mechanisms of redundancy, heterogeneity, biologic importance, and drug resistance and describe methodologic challenges that, if overcome, would significantly contribute to cancer research. Cancer Res; 75(5); 808–12. ©2015 AACR.
Geospatial Patterns in Human Papillomavirus Vaccination Uptake: Evidence from Uninsured and Publicly Insured Children in North Carolina
Authors: Trogdon Justin G. , Ahn Thomas 
Published: January 2015

Abstract
Background: Human papillomavirus (HPV) vaccination coverage is far below the national objective set by Healthy People 2020. This paper explores spatial patterns in HPV vaccination uptake.
Methods: Secondary data for publicly funded HPV vaccinations among age-eligible children from 2008 through 2013 from the North Carolina Immunization Registry (NCIR) were used in 2014 in an ecological analysis at the ZIP code tabulation area (ZCTA) level. We tested for spatial autocorrelation in unadjusted HPV vaccination rates using choropleth maps and Moran's I. We estimated nonspatial and spatial negative binomial models with spatially correlated random effects adjusted for demographic, economic, and healthcare variables drawn from the 2010 U.S. Census Bureau, 2008–2012 American Community Survey, 2010 ZIP Business Patterns, and the 2012–2013 Area Resource File.
Results: The NCIR revealed areas of especially low rates in publicly funded HPV vaccinations among uninsured and means-tested, publicly insured children. For boys, but not girls, ZCTAs tended to have HPV vaccination rates that were similar to their neighbors. This result was partially explained by included ZCTA characteristics, but not wholly.
Conclusions: To the extent that the geospatial clustering of vaccination rates is due to causal influences from one ZCTA to another (e.g., through information networks), targeting interventions to increase HPV vaccination in one area could also lead to increases in neighboring areas.
Impact: Spatial targeting of HPV vaccination, especially in clusters of low vaccination areas, could be an effective strategy to reduce the spread of HPV and related cancers. Cancer Epidemiol Biomarkers Prev; 24(3); 595–602. ©2015 AACR.
Long-term Persistence of Oral Human Papillomavirus Type 16: The HPV Infection in Men (HIM) Study
Authors: Pierce Campbell Christine M. , Kreimer Aimée R. , Lin Hui-Yi , Fulp William , O'Keefe Michael T. , Ingles Donna J. , Abrahamsen Martha , Villa Luisa L. , Lazcano-Ponce Eduardo , Giuliano Anna R. 
Published: January 2015

Abstract
Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan–Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25–42] and were followed for a median of 44.4 months (IQR, 29.9–49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4–NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. Cancer Prev Res; 8(3); 190–6. ©2015 AACR.
Peptide/MHC Tetramer–Based Sorting of CD8+ T Cells to a Leukemia Antigen Yields Clonotypes Drawn Nonspecifically from an Underlying Restricted Repertoire
Authors: Hunsucker Sally A. , McGary Colleen S. , Vincent Benjamin G. , Enyenihi Atim A. , Waugh Jennifer P. , McKinnon Karen P. , Bixby Lisa M. , Ropp Patricia A. , Coghill James M. , Wood William A. , Gabriel Don A. , Sarantopoulos Stefanie , Shea Thomas C. , Serody Jonathan S. , Alatrash Gheath , Rodriguez-Cruz Tania , Lizée Gregory , Buntzman Adam S. , Frelinger Jeffrey A. , Glish Gary L. , Armistead Paul M. 
Published: January 2015

Abstract
Testing of T cell–based cancer therapeutics often involves measuring cancer antigen–specific T-cell populations with the assumption that they arise from in vivo clonal expansion. This analysis, using peptide/MHC tetramers, is often ambiguous. From a leukemia cell line, we identified a CDK4-derived peptide epitope, UNC-CDK4-1 (ALTPVVVTL), that bound HLA-A*02:01 with high affinity and could induce CD8+ T-cell responses in vitro. We identified UNC-CDK4-1/HLA-A*02:01 tetramer+ populations in 3 of 6 patients with acute myeloid leukemia who had undergone allogeneic stem cell transplantation. Using tetramer-based, single-cell sorting and T-cell receptor β (TCRβ) sequencing, we identified recurrent UNC-CDK4-1 tetramer–associated TCRβ clonotypes in a patient with a UNC-CDK4-1 tetramer+ population, suggesting in vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRβ repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer–associated TCRβ clonotypes represented &gt;17% of the entire TCRβ repertoire—far in excess of the UNC-CDK4-1 tetramer+ frequency—indicating that the recurrent TCRβ clonotypes identified from UNC-CDK-4-1 tetramer+ cells were likely a consequence of the extremely constrained T-cell repertoire in the patient and not in vivo UNC-CDK4-1–driven clonal T-cell expansion. Mapping recurrent TCRβ clonotype sequences onto TCRβ repertoires can help confirm or refute antigen-specific T-cell expansion in vivo. Cancer Immunol Res; 3(3); 228–35. ©2015 AACR.
Functional Tuning of CARs Reveals Signaling Threshold above Which CD8+ CTL Antitumor Potency Is Attenuated due to Cell Fas–FasL-Dependent AICD
Authors: Künkele Annette , Johnson Adam J. , Rolczynski Lisa S. , Chang Cindy A. , Hoglund Virginia , Kelly-Spratt Karen S. , Jensen Michael C. 
Published: January 2015

AbstractChimeric antigen receptor (CAR) development is biased toward selecting constructs that elicit the highest magnitude of T-cell functional outputs. Here, we show that components of CAR extracellular spacer and cytoplasmic signaling domain modulate, in a cooperative manner, the magnitude of CD8+CTL activation for tumor-cell cytolysis and cytokine secretion. Unexpectedly, CAR constructs that generate the highest in vitro activity, either by extracellular spacer length tuning or by the addition of cytoplasmic signaling modules, exhibit attenuated antitumor potency in vivo, whereas CARs tuned for moderate signaling outputs mediate tumor eradication. Recursive CAR triggering renders CTLs expressing hyperactive CARs highly susceptible to activation-induced cell death (AICD) as a result of augmented FasL expression. CAR tuning using combinations of extracellular spacers and cytoplasmic signaling modules, which limit AICD of CD8+CTLs, may be a critical parameter for achieving clinical activity against solid tumors. Cancer Immunol Res; 3(4); 368–79. ©2015 AACR.
Percutaneous Epicardial Access for Mapping and Ablation Is Feasible in Patients With Prior Cardiac Surgery, Including Coronary Bypass Surgery
Authors: Killu Ammar M. , Ebrille Elisa , Asirvatham Samuel J. , Munger Thomas M. , McLeod Christopher J. , Packer Douglas L. , Friedman Paul A. , Mulpuru Siva K. 
Published: January 2015

Background—
Prior cardiac surgery, especially the presence of coronary artery bypass grafts, is thought to preclude percutaneous epicardial access (EpiAcc) and, therefore, mapping and ablation. We evaluated the feasibility and safety of EpiAcc in patients with a prior cardiac operation.

Methods and Results—
We retrospectively analyzed all patients who underwent EpiAcc for ablation for ventricular tachycardia or symptomatic premature ventricular complexes between 2004 and 2013 at Mayo Clinic, Rochester, MN. Of 162 patients who underwent EpiAcc, 18 had prior cardiac surgery (median age, 64 years, all men). This included 10 coronary artery bypass grafts, 2 epicardial implantable cardioverter defibrillator placement, 5 valve surgery, 2 septal myectomy, 1 aortic arch replacement, 1 myocardial bridge unroofing, and 1 myocardial perforation repair (3 patients had multiple procedures). Access was successful in 12 of 18; the inferior approach was used in 78%. Successful access was achieved in 6 of 10 patients with prior coronary artery bypass grafts. Adhesiolysis was required in 10 patients with the sheath, access wire, and pigtail or ablation catheter. Intraprocedural coronary angiography was performed in 8 patients. A total of 45 ventricular tachycardias/premature ventricular complexes were ablated. Thirteen patients underwent endocardial-only ablation, 2 had epicardial-only ablation, whereas 3 had endocardial–epicardial ablation. Ablation was deemed successful in 13 of 18 patients. Four patients had bleeding complications (pericardial effusion, pericardial hematoma, hemoperitoneum, and pericardial tamponade). In patients with coronary grafts, there was no evidence of acute graft disruption.

Conclusions—
Percutaneous EpiAcc is feasible in patients with previous cardiac surgery, including coronary artery bypass grafts. However, adhesiolysis is frequently required. Although the risk of coronary graft injury is low, life-threatening complications may occur.
Survival and Neurocognitive Outcomes After Cardiac Extracorporeal Life Support in Children Less Than 5 Years of Age
Authors: Ryerson Lindsay M. , Guerra Gonzalo Garcia , Joffe Ari R. , Robertson Charlene M.T. , Alton Gwen Y. , Dinu Irina A. , Granoski Don , Rebeyka Ivan M. , Ross David B. , Lequier Laurance 
Published: January 2015

Background—
Survival after pediatric cardiac extracorporeal life support (ECLS) is guarded, and neurological morbidity varies widely. Our objective is to report our 10-year experience with cardiac ECLS, including survival and kindergarten entry neurocognitive outcomes; to identify predictors of mortality or adverse neurocognitive outcomes; and to compare 2 eras, before and after 2005.

Methods and Results—

From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Sixty-four patients (65%) survived to hospital discharge, and 50 (51%) survived ≤5 years of age. Neurocognitive follow-up of survivors was completed at mean (SD) age of 52.9 (8) months using Wechsler Preschool and Primary Scale of Intelligence. Logistic regression analysis found the longer time (hours) for lactate to fall below 2 mmol/L on ECLS (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84;
P
=0.022), and the amount of platelets (mL/kg) given in the first 48 hours (hazard ratio, 1.18; 95% confidence interval, 1.06, 1.32;
P
=0.002) was independently associated with higher in-hospital mortality. Receiving ECLS after the year 2005 was independently associated with lower risk of in-hospital mortality (hazard ratio, 0.36; 95% confidence interval, 0.13, 0.99;
P
=0.048). Extracorporeal cardiopulmonary resuscitation was not independently associated with mortality or neurocognitive outcomes. Era was not independently associated with neurocognitive outcomes. The full-scale intelligence quotient of survivors without chromosomal abnormalities was 79.7 (16.6) with 25% below 2 SD of the population mean.

Conclusions—
Mortality has improved over time; time for lactate to fall on ECLS and volume of platelets transfused are independent predictors of mortality. Extracorporeal cardiopulmonary resuscitation and era were not independently associated with neurocognitive outcomes.
Persistent Recovery of Normal Left Ventricular Function and Dimension in Idiopathic Dilated Cardiomyopathy During Long‐Term Follow‐up: Does Real Healing Exist?
Authors: Merlo Marco , Stolfo Davide , Anzini Marco , Negri Francesco , Pinamonti Bruno , Barbati Giulia , Ramani Federica , Di Lenarda Andrea , Sinagra Gianfranco 
Published: January 2015

Background

An important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long‐term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in
dilated cardiomyopathy
.

Methods and Results

Persistent apparent healing was evaluated among 408 patients with
dilated cardiomyopathy
receiving tailored medical treatment and followed over the very long‐term. Persistent apparent healing was defined as
left ventricular
ejection fraction ≥50% and indexed left ventricular end‐diastolic diameter ≤33 mm/m
2
at both mid‐term (19±4 months) and long‐term (103±9 months) follow‐up. At mid‐term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9% of the whole population) showed persistent apparent healing at long‐term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant–free survival at very long‐term follow‐up (95% versus 71%;
P
=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very long term, 37% of this subgroup experienced deterioration of
left ventricular
systolic function, and 5% died or had heart transplantation.

Conclusions

Persistent long‐term apparent healing was evident in a remarkable proportion of
dilated cardiomyopathy
patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of
left ventricular
function over the very long term, highlighting the relevance of serial and individualized follow‐up in all patients with
dilated cardiomyopathy
, especially considering the absence of predictors for long‐term apparent healing.