bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSV-sr39TK Positron Emission Tomography and Suicide Gene Elimination of Human Hematopoietic Stem Cells and Their Progeny in Humanized Mice
Authors: Gschweng Eric H. , McCracken Melissa N. , Kaufman Michael L. , Ho Michelle , Hollis Roger P. , Wang Xiaoyan , Saini Navdeep , Koya Richard C. , Chodon Thinle , Ribas Antoni , Witte Owen N. , Kohn Donald B. 
Published: July 2014

Abstract
Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR–bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173–83. ©2014 AACR.
Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History
Authors: Karlsson Anna , Ringnér Markus , Lauss Martin , Botling Johan , Micke Patrick , Planck Maria , Staaf Johan 
Published: July 2014

Abstract
Purpose: Cigarette smoking is the major pathogenic factor for lung cancer. The precise mechanisms of tobacco-related carcinogenesis and its effect on the genomic and transcriptional landscape in lung cancer are not fully understood.
Experimental Design: A total of 1,398 (277 never-smokers and 1,121 smokers) genomic and 1,449 (370 never-smokers and 1,079 smokers) transcriptional profiles were assembled from public lung adenocarcinoma cohorts, including matched next-generation DNA-sequencing data (n = 423). Unsupervised and supervised methods were used to identify smoking-related copy-number alterations (CNAs), predictors of smoking status, and molecular subgroups.
Results: Genomic meta-analyses showed that never-smokers and smokers harbored a similar frequency of total CNAs, although specific regions (5q, 8q, 16p, 19p, and 22q) displayed a 20% to 30% frequency difference between the two groups. Importantly, supervised classification analyses based on CNAs or gene expression could not accurately predict smoking status (balanced accuracies ∼60% to 80%). However, unsupervised multicohort transcriptional profiling stratified adenocarcinomas into distinct molecular subgroups with specific patterns of CNAs, oncogenic mutations, and mutation transversion frequencies that were independent of the smoking status. One subgroup included approximately 55% to 90% of never-smokers and approximately 20% to 40% of smokers (both current and former) with molecular and clinical features of a less aggressive and smoking-unrelated disease. Given the considerable intragroup heterogeneity in smoking-defined subgroups, especially among former smokers, our results emphasize the clinical importance of accurate molecular characterization of lung adenocarcinoma.
Conclusions: The landscape of smoking-related CNAs and transcriptional alterations in adenocarcinomas is complex, heterogeneous, and with moderate differences. Our results support a molecularly distinct less aggressive adenocarcinoma entity, arising in never-smokers and a subset of smokers. Clin Cancer Res; 20(18); 4912–24. ©2014 AACR.
Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility
Authors: Pentcheva-Hoang Tsvetelina , Simpson Tyler R. , Montalvo-Ortiz Welby , Allison James P. 
Published: July 2014

Abstract
It is now clear that anti–CTLA-4 (α-CTLA-4) antibodies stimulate tumor immunity either by relieving inhibition of effector T-cell function or by depletion of regulatory T cells (Treg). Several recent reports, however, have suggested that these antibodies may deliver a “go” signal to effector T cells, thus interrupting T-cell receptor signaling and subsequent T-cell activation. We examined the behavior of melanoma-specific CD8+ pmel-1 T cells in the B16/BL6 mouse model using intravital microscopy. Pmel-1 velocities in progressively growing tumors were lower than their velocities in tumors given a therapeutic combination that included α-CTLA-4 antibodies, suggesting that successful immunotherapy correlates with greater T-cell motility. When α-CTLA-4 antibodies were injected during imaging, the velocities of pmel-1 T cells in tumor-draining lymph nodes also increased. Because α-CTLA-4 Fab fragments had the same effect as the intact antibody, the higher T-cell motility does not seem to be due to CTLA-4 inhibitory signaling but rather to the release of nonproductive stable interactions between tumor-infiltrating T cells and tumor targets or antigen-presenting cells subsequent to CTLA-4 blockade. This phenomenon resembles the recently described reversal of the antiviral T-cell motility paralysis by programmed death 1 (PD-1)–specific antibodies during T-cell exhaustion in persistent viral infections. Cancer Immunol Res; 2(10); 970–80. ©2014 AACR.
Developing and sustaining a healthy school community: Essential elements identified by school health champions
Authors: Stolp Sean , Wilkins Emma , Raine Kim D 
Published: July 2014

Background: Comprehensive School Health (CSH) approaches to developing a healthy school community can be effective in supporting chronic disease prevention while positively impacting on student behaviour and academic performance. Although a CSH framework provides principles for action, there is a lack of evidence regarding the processes that best facilitate CSH work, and enable action. Objective: The purpose of this study was to identify and describe the elements of practice-based evidence that contribute to the success and sustainability of healthy school communities, through the identification of positive practices and lessons learned from a sample of projects in Alberta, Canada. Setting: School communities in Alberta, Canada. Design and methods: Key individuals from a list of operating CSH projects were invited for interview. An exploratory, qualitative design examined the perspectives of these ‘school health champions’. A total of 12 one-on-one interviews and one focus group with seven participants were completed, resulting in input from 19 individuals in total. Results: Elements to develop and sustain a healthy school community fall into one of two categories: (1) stakeholder buy-in and (2) adequate resources in the form of human resources, partnerships and peer support. Participants identified successful strategies for establishing buy-in from administrators, teachers, parents and students. Conclusion: To effectively mobilise a comprehensive school health framework, practical strategies for implementation are needed. While some of these strategies are context-specific, practice-based evidence that transcends the local context does exist and can be used more widely to support the development of a healthy school community.
An Anatomical Study Comparing Two Surgical Approaches for Isolated Talonavicular Arthrodesis
Authors: Higgs Zoe , Jamal Bilal , Fogg Quentin A. , Kumar C. Senthil 
Published: July 2014

Background: Two operative approaches are commonly used for isolated talonavicular arthrodesis: the medial and the dorsal approach. It is recognized that access to the lateral aspect of the talonavicular joint can be limited when using the medial approach, and it is our experience that using the dorsal approach addresses this issue. We performed an anatomical study using cadaver specimens, to compare the amount of articular surface that can be accessed by each operative approach. Methods: Medial and dorsal approaches to the talonavicular joint were performed on each of 11 cadaveric specimens (10 fresh frozen, 1 embalmed). Distraction of the joint was performed as used intraoperatively and the accessible area of articular surfaces was marked for each of the 2 approaches using a previously reported technique. Disarticulation was performed and the marked surface area was quantified using an immersion digital microscribe, allowing a 3-dimensional virtual model of the articular surfaces to be assessed. Results: The median percentage of total accessible talonavicular articular surface area for the medial and dorsal approaches was 71% and 92%, respectively (Wilcoxon signed-rank test, P < .001). Conclusion: This study provides quantifiable measurements of the articular surface accessible by the medial and dorsal approaches to the talonavicular joint. Clinical Relevance: These data support for the use of the dorsal approach for talonavicular arthrodesis, particularly in cases where access to the lateral half of the joint is necessary.
Feasibility and Outcome of Inferior Extensor Retinaculum Reinforcement in Modified Broström Procedures
Authors: Jeong Bi O , Kim Myung Seo , Song Wook Jae , SooHoo Nelson F. 
Published: July 2014

Background: The purpose of this study was to assess the feasibility of inferior extensor retinaculum (IER) reinforcement and analyze differences in clinical and radiographic outcomes based on whether or not IER reinforcement was performed in modified Broström procedures. Methods: Forty-one patients (41 ankles) who underwent ankle reconstruction with either a Broström procedure or modified Broström with IER reinforcement were included in this prospective study. During Broström procedures, feasibility of IER reinforcement was recorded. Clinical and radiographic outcomes were analyzed between modified Broström procedures (MBP group) in which IER reinforcement was feasible and Broström procedures (BP group) in which IER reinforcement was not feasible. Results: IER reinforcement was feasible in 31 cases (75.6%) and not feasible in 10 cases (24.4%) due to anatomic variations. The American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved in the MBP group from a preoperative mean of 66.3 to a postoperative mean of 89.4. In the BP group, the score increased from 71.3 to 89.8. The radiographic outcomes assessed by stress radiographs demonstrated that talar anterior translation and talar tilt improved from 6.3 mm to 4.6 mm and from 9.0 degrees to 5.0 degrees, respectively, in the MBP group. In the BP group, talar anterior translation improved from 6.9 mm to 4.9 mm and talar tilt, from 9.5 degrees to 4.9 degrees. No statistically significant difference was observed between the 2 groups. Conclusion: IER reinforcement was feasible in 75.6% of patients in whom modified Broström procedures had been planned. Postoperative clinical and radiographic outcomes were not significantly different based on whether or not IER reinforcement was performed. These findings suggest that isolated ligament reconstruction without IER may be sufficient to restore ankle stability. Level of Evidence: Level II, cohort study.
Statins, the renin–angiotensin–aldosterone system and hypertension – a tale of another beneficial effect of statins
Authors: Drapala Adrian , Sikora Mariusz , Ufnal Marcin 
Published: July 2014

Background: Statins, a class of lipid lowering drugs, decrease mortality associated with cardiovascular events. As hypercholesterolemia is often accompanied by hypertension, a large number of patients receive therapy with statins and antihypertensive drugs which act via the renin–angiotensin–aldosterone system (RAAS). New guidelines published by the American Heart Association and American College of Cardiology on the treatment of dyslipidaemia and the reduction of atherosclerotic cardiovascular risk, which use a risk prediction algorithm based on risk factors such as hypertension but not low-density lipoprotein (LDL) level, may even further increase the number of patients receiving such concomitant therapy. Method: In this paper we review studies on an interaction between statins, the RAAS and antihypertensive drugs acting via the RAAS. Result: Accumulating evidence suggests that the combination of statins and drugs affecting the RAAS exerts a synergistic effect on the circulatory system. For example, statins may lower arterial blood pressure and augment the effect of antihypertensive drugs acting via the RAAS. Statins may interact with the RAAS in a number of ways i.e. to decrease the expression of receptors for angiotensin II (Ang II), inhibit the Ang II-dependent intracellular signalling, reduce the RAAS-dependent oxidative stress and inflammation as well as inhibit the synthesis of Ang II and aldosterone. Conclusion: Although statins given either alone or together with antihypertensive drugs acting via the RAAS may lower arterial blood pressure, further research is needed to evaluate the mechanisms and their therapeutic significance.
Characterizing Accuracy and Precision of Glucose Sensors and Meters
Authors: Rodbard David 
Published: July 2014

Background: There is need for a method to describe precision and accuracy of glucose measurement as a smooth continuous function of glucose level rather than as a step function for a few discrete ranges of glucose. We propose and illustrate a method to generate a “Glucose Precision Profile” showing absolute relative deviation (ARD) and /or %CV versus glucose level to better characterize measurement errors at any glucose level. Method: We examine the relationship between glucose measured by test and comparator methods using linear regression. We examine bias by plotting deviation = (test – comparator method) versus glucose level. We compute the deviation, absolute deviation (AD), ARD, and standard deviation (SD) for each data pair. We utilize curve smoothing procedures to minimize the effects of random sampling variability to facilitate identification and display of the underlying relationships between ARD or %CV and glucose level. Results: AD, ARD, SD, and %CV display smooth continuous relationships versus glucose level. Estimates of MARD and %CV are subject to relatively large errors in the hypoglycemic range due in part to a markedly nonlinear relationship with glucose level and in part to the limited number of observations in the hypoglycemic range. Conclusions: The curvilinear relationships of ARD and %CV versus glucose level are helpful when characterizing and comparing the precision and accuracy of glucose sensors and meters.
Raman Spectroscopy as a Promising Tool for Noninvasive Point-of-Care Glucose Monitoring
Authors: Scholtes-Timmerman Maarten J. , Bijlsma Sabina , Fokkert Marion J. , Slingerland Robbert , van Veen Sjaak J. F. 
Published: July 2014

Background: Self-monitoring of glucose is important for managing diabetes. Noninvasive glucose monitors are not yet available, but patients would benefit highly from such a device. Methods: We present results that may lead to a novel, point-of-care noninvasive system to measure blood glucose based on Raman spectroscopy. A hospitalized cohort of 111 subjects was measured using a custom-made Raman spectrometer system. Blood glucose reference samples were used to correlate Raman data to glucose levels, using advanced preprocessing and analysis algorithms. Results: A correlation coefficient ( R2) of .83 was found correlating independent Raman-based predictions on reference blood glucose for the full cohort. Stratification of the cohort in gender-specific groups raised correlation levels to .88 (females) and .94 (males). Glucose could be measured noninvasively with average errors as low as 0.9 mM. Conclusion: We conclude that this novel system shows promising results for the advance of noninvasive, point-of-care glucose monitoring.
Osteochondral Lesions of the Ankle Joint in Professional Soccer Players
Authors: Valderrabano Victor , Barg Alexej , Alattar Abdulhameed , Wiewiorski Martin 
Published: July 2014

Acute and recurrent ankle sprains and other trauma to the ankle joint are common injuries in soccer and can be accompanied by or result in osteochondral lesions of the ankle joint, majorly of the talus. Conservative treatment frequently fails. Several operative treatment techniques exist; however, the choice of the right procedure is difficult due to lack of literature with a high level of evidence. We present our treatment method for acute and chronic ankle osteochondral lesions with cystic formation approached by a new surgical technique combining bone plasty and a collagen matrix (autologous matrix-induced chondrogenesis). Levels of Evidence: Therapeutic, Level IV: Case series
Joint Salvage After Neglected Intra-Articular Physeal Fracture of the Hallux in High-Level Gymnasts
Authors: Bariteau Jason T. , Murillo Diana Montoya , Tenenbaum Shay A. , Brodsky James W. 
Published: July 2014

Chronic sports-related injuries involving the hallux are well known in adult populations. However, they are less frequently described in adolescents. We present 2 cases of elite-level gymnasts with neglected Salter–Harris IV fractures involving the proximal phalanx of the great toe following a severe hyperextension injury to the metatarsophalangeal joint. Both were successfully treated with open reduction and internal fixation with return to pre-injury level of activity, improvement in outcome scores, and demonstration of no disability from injury 2 years after surgical intervention. Levels of Evidence: Therapeutic, Level IV: Case Series
Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models
Authors: Florek Mareike , Sega Emanuela I. , Leveson-Gower Dennis B. , Baker Jeanette , Müller Antonia M. S. , Schneidawind Dominik , Meyer Everett , Negrin Robert S. 
Published: July 2014

Key Points
Prophylactic ECP protects against GVHD in a murine BMT model. ECP provides apoptotic signals that promote tolerance through dendritic cells and Tregs.
Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito
Authors: Nagamura Yuko , Terawaki Kiyoshi , Uezono Yasuhito , Tsukada Toshihiko 
Published: July 2014

Abstract

Background
Rikkunshito is a traditional Japanese herbal medicine that is used to treat appetite loss associated with cancer and other disorders. The formulation contains various constituents that influence cell signaling, and rikkunshito may accordingly affect human homeostasis through multiple regulatory pathways, including those governed by the endocrine system. We investigated the actions of rikkunshito on catecholamine release from PC12 cells, an adrenal chromaffin cell line.

Methods
The actions of rikkunshito on PC12 cells were evaluated by measuring intracellular cAMP levels, tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP) mRNA expression levels, and catecholamine levels in the culture medium. The transcriptional activation of VIP gene by rikkunshito was assessed by using a VIP promoter-driven reporter gene assay.

Results
Rikkunshito dose-dependently enhanced forskolin-induced elevations in cAMP in PC12 cells, and also increased the gene expression of TH and VIP. The transcriptional activation of VIP gene by rikkunshito was confirmed. Norepinephrine and dopamine secretion into the culture medium of PC12 cells were also dose-dependently augmented by rikkunshito and/or forskolin, but experiments with a protein kinase C (PKC) activator and a phosphodiesterase inhibitor revealed that the effects of rikkunshito were not simply due to the modulation of PKC or phosphodiesterase activity.

Conclusions
These findings suggest that rikkunshito enhances the release of catecholamines by a novel mechanism involving cAMP.
Expression Profiling of Genes Modulated by Minocycline in a Rat Model of Neuropathic Pain
Authors: Rojewska Ewelina , Korostynski Michal , Przewlocki Ryszard , Przewlocka Barbara , Mika Joanna 
Published: July 2014

Background: The molecular mechanisms underlying neuropathic pain are constantly being studied to create new opportunities to prevent or alleviate neuropathic pain. The aim of our study was to determine the gene expression changes induced by sciatic nerve chronic constriction injury (CCI) that are modulated by minocycline, which can effectively diminish neuropathic pain in animal studies. The genes associated with minocycline efficacy in neuropathic pain should provide insight into the etiology of neuropathic pain and identify novel therapeutic targets. Results: We screened the ipsilateral dorsal part of the lumbar spinal cord of the rat CCI model for differentially expressed genes. Out of 22,500 studied transcripts, the abundance levels of 93 transcripts were altered following sciatic nerve ligation. Percentage analysis revealed that 54 transcripts were not affected by the repeated administration of minocycline (30 mg/kg, i.p.), but the levels of 39 transcripts were modulated following minocycline treatment. We then selected two gene expression patterns, B1 and B2. The first transcription pattern, B1, consisted of 10 mRNA transcripts that increased in abundance after injury, and minocycline treatment reversed or inhibited the effect of the injury; the B2 transcription pattern consisted of 7 mRNA transcripts whose abundance decreased following sciatic nerve ligation, and minocycline treatment reversed the effect of the injury. Based on the literature, we selected seven genes for further analysis: Cd40, Clec7a, Apobec3b, Slc7a7, and Fam22f from pattern B1 and Rwdd3 and Gimap5 from pattern B2. Additionally, these genes were analyzed using quantitative PCR to determine the transcriptional changes strongly related to the development of neuropathic pain; the ipsilateral DRGs (L4-L6) were also collected and analyzed in these rats using qPCR. Conclusion: In this work, we confirmed gene expression alterations previously identified by microarray analysis in the spinal cord and analyzed the expression of selected genes in the DRG. Moreover, we reviewed the literature to illustrate the relevance of these findings for neuropathic pain development and therapy. Further studies are needed to elucidate the roles of the individual genes in neuropathic pain and to determine the therapeutic role of minocycline in the rat neuropathic pain model.
Stem cell delivery of therapies for brain disorders
Authors: Aleynik Alexander , Gernavage Kevin M , Mourad Yasmine SH , Sherman Lauren S , Liu Katherine , Gubenko Yuriy A , Rameshwar Pranela 
Published: July 2014

AbstractThe blood brain barrier (BBB) poses a problem to deliver drugs for brain malignancies and neurodegenerative disorders. Stem cells such as neural stem cells (NSCs) and mesenchymal stem cells (MSCs) can be used to delivery drugs or RNA to the brain. This use of methods to bypass the hurdles of delivering drugs across the BBB is particularly important for diseases with poor prognosis such as glioblastoma multiforme (GBM). Stem cell treatment to deliver drugs to neural tumors is currently in clinical trial. This method, albeit in the early phase, could be an advantage because stem cells can cross the BBB into the brain. MSCs are particularly interesting because to date, the experimental and clinical evidence showed ‘no alarm signal’ with regards to safety. Additionally, MSCs do not form tumors as other more primitive stem cells such as embryonic stem cells. More importantly, MSCs showed pathotropism by migrating to sites of tissue insult. Due to the ability of MSCs to be transplanted across allogeneic barrier, drug‐engineered MSCs can be available as off‐the‐shelf cells for rapid transplantation. This review discusses the advantages and disadvantages of stem cells to deliver prodrugs, genes and RNA to treat neural disorders.