bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using urinary bFGF and TIMP3 levels to predict the presence of juvenile pilocytic astrocytoma and establish a distinct biomarker signature
Authors: Pricola Fehnel Katie , Duggins-Warf Micah , Zurakowski David , McKee-Proctor Maxwell , Majumder Rajarshi , Raber Michael , Han Xuezhe , Smith Edward R. 
Published: June 2016

OBJECTIVE
The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers.

METHODS
Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses.

RESULTS
Using optimal urinary cutoff values of bFGF > 1.0 pg/μg and TIMP3 > 3.5 pg/μg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size.

CONCLUSIONS
This study identifies 2 urinary biomarkers—bFGF and TIMP3—that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.
Accuracy of operating neurosurgeons' prediction of functional levels after intracranial tumor surgery
Authors: Sagberg Lisa Millgård , Drewes Christina , Jakola Asgeir S. , Solheim Ole 
Published: June 2016

OBJECTIVE
In the absence of practical and reliable prognostic tools in intracranial tumor surgery, decisions regarding patient selection, patient information, and surgical management are usually based on neurosurgeons' clinical judgment, which may be influenced by personal experience and knowledge. The objective of this study was to assess the accuracy of the operating neurosurgeons' predictions about patients' functional levels after intracranial tumor surgery.

METHODS
In a prospective single-center study, the authors included 299 patients who underwent intracranial tumor surgery between 2011 and 2015. The operating neurosurgeons scored their patients' expected functional level at 30 days after surgery using the Karnofsky Performance Scale (KPS). The expected KPS score was compared with the observed KPS score at 30 days.

RESULTS
The operating neurosurgeons underestimated their patients' future functional level in 15% of the cases, accurately estimated their functional levels in 23%, and overestimated their functional levels in 62%. When dichotomizing functional levels at 30 days into dependent or independent functional level categories (i.e., KPS score < 70 or ≥ 70), the predictive accuracy was 80%, and the surgeons underestimated and overestimated in 5% and 15% of the cases, respectively. In a dichotomization based on the patients' ability to perform normal activities (i.e., KPS score < 80 or ≥ 80), the predictive accuracy was 57%, and the surgeons underestimated and overestimated in 3% and 40% of cases, respectively. In a binary regression model, the authors found no predictors of underestimation, whereas postoperative complications were an independent predictor of overestimation (p = 0.01).

CONCLUSIONS
Operating neurosurgeons often overestimate their patients' postoperative functional level, especially when it comes to the ability to perform normal activities at 30 days. This tendency to overestimate surgical outcomes may have implications for clinical decision making and for the accuracy of patient information.
Establishment and characterization of a chordoma cell line from the tissue of a patient with dedifferentiated-type chordoma
Authors: Kim Jeong-Yub , Lee Jongsun , Koh Jae-Soo , Park Myung-Jin , Chang Ung-Kyu 
Published: June 2016

OBJECTIVE
Chordoma is a rare bone tumor of the axial skeleton believed to originate from the remnants of the embryonic notochord. The available tumor cells are characteristically physaliferous and express brachyury, a transcription factor critical for mesoderm specification. Although chordomas are histologically not malignant, treatments remain challenging because they are resistant to radiation therapy and because wide resection is impossible in most cases. Therefore, a better understanding of the biology of chordomas using established cell lines may lead to the advancement of effective treatment strategies. The authors undertook a study to obtain this insight.

METHODS
Chordoma cells were isolated from the tissue of a patient with dedifferentiated-type chordoma (DTC) that had recurred. Cells were cultured with DMEM/F12 containing 10% fetal bovine serum and antibiotics (penicillin and streptomycin). Cell proliferation rate was measured by MTS assay. Cell-cycle distribution and cell surface expression of proteins were analyzed by fluorescence-activated cell sorting (FACS) analysis. Expression of proteins was analyzed by Western blot and immunocytochemistry. Radiation resistance was measured by clonogenic survival assay. Tumor formation was examined by injection of chordoma cells at hindlimb of nude mice.

RESULTS
The putative (DTC) cells were polygonal and did not have the conventional physaliferous characteristic seen in the U-CH1 cell line. The DTC cells exhibited similar growth rate and cell-cycle distribution, but they exhibited higher clonogenic activity in soft agar than U-CH1 cells. The DTC cells expressed high levels of platelet-derived growth factor receptor–β and a low level of brachyury and cytokeratins; they showed higher expression of stemness-related and epithelial to mesenchymal transition–related proteins than the U-CH1 cells. Intriguingly, FACS analysis revealed that DTC cells exhibited marginal surface expression of CD24 and CD44 and high surface expression of CXCR4 in comparison to U-CH1 cells. In addition, blockade of CXCR4 with its antagonist AMD3100 effectively suppressed the growth of both cell lines. The DTC cells were more resistant to paclitaxel, cisplatin, etoposide, and ionizing radiation than the U-CH1 cells. Injection of DTC cells into the hindlimb region of nude mice resulted in the efficient formation of tumors, and the histology of xenograft tumors was very similar to that of the original patient tumor.

CONCLUSIONS
The use of the established DTC cells along with preestablished cell lines of chordoma may help bring about greater understanding of the mechanisms underlying the chordoma that will lead to therapeutic strategies targeting chordomas.
Surgical treatment of degenerative and traumatic spinal diseases with expandable screws in patients with osteoporosis: 2-year follow-up clinical study
Authors: Gazzeri Roberto , Roperto Raffaelino , Fiore Claudio 
Published: June 2016

OBJECTIVE
Pedicle screw instrumentation of the osteoporotic spine carries an increased risk of screw loosening, pullout, and fixation failure. A variety of techniques have been used clinically to improve pedicle screw fixation in the presence of compromised bone. Pedicle screws may be augmented with cement, but this may lead to cement leakage and result in disastrous consequences. To avoid these complications, a multiaxial expandable pedicle screw has been developed. This was a prospective, single-center study designed to evaluate the clinical results of patients with osteoporosis with traumatic and degenerative spinal diseases treated with expandable pedicle screws.

METHODS
Thirty-three patients (mean age 61.4 years) with osteoporosis and traumatic or degenerative spinal diseases underwent spinal posterior fixation with expandable screws. Preoperative and postoperative visual analog scale (VAS) for pain and Oswestry Disability Index (ODI) questionnaire scores were obtained. The immediate postoperative screw position was measured and compared with the final position on lateral plain radiographs and axial CT scans at the 1- and 2-year follow-up examinations.

RESULTS
A total of 182 pedicle screws were used, including 174 expandable and 8 regular screws. The mean preoperative patient VAS score improved from 8.2 to 3.6 after surgery. The mean ODI score improved from 83.7% before surgery to 29.7% after the operation and to 36.1% at the final follow-up. No screw migration had occurred at the 1-year follow-up, but 1 screw breakage/migration was visualized on spinal radiography at the 2-year follow-up.

CONCLUSIONS
The results of this study show that the multiaxial expandable pedicle screw is a safe and practical technique for patients with osteoporosis and various spinal diseases and adds a valuable tool to the armamentarium of spinal instrumentation.
Recovery of functional connectivity of the sensorimotor network after surgery for diffuse low-grade gliomas involving the supplementary motor area
Authors: Vassal Matthieu , Charroud Céline , Deverdun Jérémy , Le Bars Emmanuelle , Molino François , Bonnetblanc Francois , Boyer Anthony , Dutta Anirban , Herbet Guillaume , Moritz-Gasser Sylvie , Bonafé Alain , Duffau Hugues , de Champfleur Nicolas Menjot 
Published: June 2016

OBJECTIVE
The supplementary motor area (SMA) syndrome is a well-studied lesional model of brain plasticity involving the sensorimotor network. Patients with diffuse low-grade gliomas in the SMA may exhibit this syndrome after resective surgery. They experience a temporary loss of motor function, which completely resolves within 3 months. The authors used functional MRI (fMRI) resting state analysis of the sensorimotor network to investigate large-scale brain plasticity between the immediate postoperative period and 3 months' follow-up.

METHODS
Resting state fMRI was performed preoperatively, during the immediate postoperative period, and 3 months postoperatively in 6 patients with diffuse low-grade gliomas who underwent partial surgical excision of the SMA. Correlation analysis within the sensorimotor network was carried out on those 3 time points to study modifications of its functional connectivity.

RESULTS
The results showed a large-scale reorganization of the sensorimotor network. Interhemispheric connectivity was decreased in the postoperative period, and increased again during the recovery process. Connectivity between the lesion side motor area and the contralateral SMA rose to higher values than in the preoperative period. Intrahemispheric connectivity was decreased during the immediate postoperative period and had returned to preoperative values at 3 months after surgery.

CONCLUSIONS
These results confirm the findings reported in the existing literature on the plasticity of the SMA, showing large-scale modifications of the sensorimotor network, at both inter- and intrahemispheric levels. They suggest that interhemispheric connectivity might be a correlate of SMA syndrome recovery.
Changing of the guard: reducing infection when replacing neural pacemakers
Authors: Pepper Joshua , Meliak Lara , Akram Harith , Hyam Jonathan , Milabo Catherine , Candelario Joseph , Foltynie Thomas , Limousin Patricia , Curtis Carmel , Hariz Marwan , Zrinzo Ludvic 
Published: June 2016

OBJECTIVE
Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution.

METHODS
Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up.

RESULTS
The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003).

CONCLUSIONS
This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.
Efficacy of microsurgical tumor removal for treatment of patients with intracanalicular vestibular schwannoma presenting with disabling vestibular symptoms
Authors: Samii Madjid , Metwali Hussam , Gerganov Venelin 
Published: June 2016

OBJECTIVEThe aim of this study was to analyze the efficacy and risks of microsurgery via the hearing-preserving retrosigmoid approach in patients with intracanalicular vestibular schwannoma (VS) suffering from disabling vestibular symptoms, with special attention to vertigo.METHODSThis is a retrospective analysis of 19 patients with intracanalicular VS and disabling vestibular dysfunction as the main or only symptom (Group A). All of the patients reported having had disabling vertigo attacks. Subjective evaluation of the impairment of patients was performed before surgery, 3 weeks after surgery, 3 months after surgery, and 1 year after surgery, using the Dizziness Handicap Inventory (DHI). The main outcome measures were improvement in quality of life as measured using the DHI, and general and functional outcomes, in particular facial function and hearing. Patient age, preoperative tumor size, preoperative DHI score, and preservation of the nontumorous vestibular nerve were tested using a multivariate regression analysis to determine factors affecting the postoperative DHI score. The Mann-Whitney U-test was used to compare the postoperative DHI score at 3 weeks, 3 months, and 1 year after surgery with a control group of 19 randomly selected patients with intracanalicular VSs, who presented without vestibular symptoms (Group B). The occurrence of early postoperative discrete vertigo attacks was also compared between groups.RESULTSThe preoperative DHI score was ≥ 54 in all patients. All patients reported having had disabling rotational vertigo before surgery. The only significant factor to affect the DHI outcome 3 weeks and 3 months after surgery was the preoperative DHI score. The DHI outcome after 1 year was not affected by the preoperative DHI score. Compared with the control group, the DHI score at 3 weeks and 3 months after surgery was significantly worse. There was no significant difference between the groups after 1 year. Vertigo was improved in all patients and completely resolved after 1 year in 17 patients.CONCLUSIONSDisabling vestibular dysfunction that affects quality of life should be considered an indication for surgery, even in otherwise asymptomatic patients with intracanalicular VS. Surgical removal of the tumor is safe and very effective in regard to symptom relief. All patients had excellent facial nerve function within 1 year after surgery, with a very good chance of hearing preservation.
Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies
Authors: Spiess Philippe E. , Dhillon Jasreman , Baumgarten Adam S. , Johnstone Peter A. , Giuliano Anna R. 
Published: June 2016

ABSTRACTAnswer questions and earn CME/CNESquamous cell carcinoma (SCC) of the penis is a rare malignancy in the United States, with a significantly higher incidence—up to 20 to 30 times greater—in areas of Africa and South America. This can be explained in part by the significantly greater prevalence of sexually transmitted diseases among high‐risk males often having unprotected sex with multiple sexual partners. Human papillomavirus (HPV) has been implicated as the infectious pathway by which several these penile neoplasms originate from precursor lesions. In this regard, a fundamental understanding of HPV in penile carcinogenesis can have meaningful implications in understanding 1) the diagnosis of HPV‐related precursor penile lesions, 2) targeting HPV‐specific molecular pathways, and 3) cancer prevention. Using vaccination programs not only may improve patient outcomes but also may minimize the need for highly aggressive and often debilitating surgical resection. CA Cancer J Clin 2016;66:481–495. © 2016 American Cancer Society.
A reexamination of the North American Crepis agamic complex and comparison with the findings of Babcock and Stebbins’ classic biosystematic monograph
Authors: Sears Christopher J. , Whitton Jeannette 
Published: June 2016

PREMISE OF THE STUDY:Babcock and Stebbins coined the term agamic complex in their 1938 monograph of the North American Crepis agamic complex. Despite the historical role that this complex holds in the evolutionary literature, it has not been reexamined in over 75 years. We present a thorough reevaluation of the complex to test hypotheses proposed by Babcock and Stebbins about its origins and spread, the relationships of diploids, and the nature and origins of polyploids.METHODS:We used flow cytometry to infer ploidy of roughly 600 samples spanning the morphological and taxonomic diversity of the complex and a phylogenetic analysis of plastid DNA variation to infer maternal relationships among diploids and to infer maternal origins of polyploids.KEY RESULTS:We identified populations of all seven recognized diploids plus one new lineage. Phylogenetic analysis of plastid DNA variation in diploids revealed a well‐resolved, but moderately supported phylogeny, with evidence for monophyly of the North America Crepis agamic complex and no evidence of widespread homoploid hybridization. Polyploids showed evidence of multiple origins and a pattern of frequent local co‐occurrence consistent with repeated colonization of suitable sites.CONCLUSIONS:Our findings agree broadly with the distribution and variation of ploidy within and among species described by Babcock and Stebbins. One key difference is finding support for monophyly of North American species, and refuting their hypothesis of polyphyly. Our results provide an explicit phylogenetic framework for further study of this classic agamic complex.
Molecular evidence supports ancient long‐distance dispersal for the amphi‐Atlantic disjunction in the giant yellow shrimp plant (Barleria oenotheroides)
Authors: Martín‐Bravo Santiago , Daniel Thomas F. 
Published: June 2016

PREMISE OF THE STUDY:Barleria is a large, pantropical genus of ca. 265 species mainly distributed in the Old World with only one species, B. oenotheroides, extending to the neotropics. This amphi‐Atlantic disjunction, frequently displayed by pantropical taxa, has been traditionally explained with vicariance or geodispersal hypotheses and increasingly with long‐distance dispersal. The native status of this species in the New World is controversial.METHODS:A molecular phylogeographic study based on the nuclear ribosomal ITS region and plastid trnL‐F, rps16, and trnS‐G sequences was done to clarify the origin of this tropical intercontinental disjunction. Divergence times were estimated with various analytical approaches, including different markers and primary calibration points.KEY RESULTS:Divergence ages estimated for Barleria lineages disagree with vicariance or geodispersal hypotheses. Genetic differentiation of American vs. African populations of B. oenotheroides does not support a recent anthropogenic introduction to the New World. Our data suggest ancient long‐distance dispersal from the Old to the New World probably during the Pliocene or Upper Miocene. The number of dispersal events remains unclear.CONCLUSIONS:Our study demonstrates the native status of Barleria in the New World, resolving one of only three presumed natural Old World–New World disjunctions at the species level among Acanthaceae. This case constitutes a further documented example of the “out‐of‐Africa” pattern in the family, despite their lack of documented assisted‐dispersal syndromes, and highlights the importance of long‐distance dispersal to explain pantropical distributions in many families.
CHALLENGING SOME CONTEMPORARY VIEWS OF CORONAL MASS EJECTIONS. I. THE CASE FOR BLAST WAVES
Authors: Howard T. A. , Pizzo V. J. 
Published: June 2016

ABSTRACT
Since the closure of the “solar flare myth” debate in the mid-1990s, a specific narrative of the nature of coronal mass ejections (CMEs) has been widely accepted by the solar physics community. This narrative describes structured magnetic flux ropes at the CME core that drive the surrounding field plasma away from the Sun. This narrative replaced the “traditional” view that CMEs were blast waves driven by solar flares. While the flux rope CME narrative is supported by a vast quantity of measurements made over five decades, it does not adequately describe every observation of what have been termed CME-related phenomena. In this paper we present evidence that some large-scale coronal eruptions, particularly those associated with EIT waves, exhibit characteristics that are more consistent with a blast wave originating from a localized region (such as a flare site) rather than a large-scale structure driven by an intrinsic flux rope. We present detailed examples of CMEs that are suspected blast waves and flux ropes, and show that of our small sample of 22 EIT-wave-related CMEs, 91% involve a blast wave as at least part of the eruption, and 50% are probably blast waves exclusively. We conclude with a description of possible signatures to look for in determining the difference between the two types of CMEs and with a discussion on modeling efforts to explore this possibility.