bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multipotent Stromal Cell Therapy for Cavernous Nerve Injury-Induced Erectile Dysfunction
Authors: Albersen Maarten , Kendirci Muammer , Van der Aa Frank , Hellstrom Wayne J.G. , Lue Tom F. , Spees Jeffrey L. 
Published: December 2011

ABSTRACT

Introduction
Erectile dysfunction (ED) following radical prostatectomy (RP) is a result of inadvertent damage to the cavernous nerves that run close to the prostate capsula. The mechanisms behind the development of post-RP ED are increasingly recognized and include cavernosal fibrosis and cavernosal smooth muscle apoptosis, resulting from cavernous nerve degeneration due to neuropraxia. In recent years, cell-based therapies have received increasing attention regarding their potential for recovery of erectile function following cavernous nerve injury (CNI). Multipotent stromal cells (MSCs) are an attractive cell source for this application based on their regenerative potential and their clinical applicability.

Aim
To review available evidence on the efficacy and mechanisms of action of MSC application for the treatment of ED, with an emphasis on ED following CNI.

Methods
A nonsystematic review was conducted on the available English literature between 1966 and 2011 on the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar, and PubMed.

Results
MSCs from both bone marrow and adipose tissue have shown beneficial effects in a variety of animal models for ED. While MSC application in chronic disease models such as diabetes, aging, and hyperlipidemia may result in cell engraftment and possibly MSC differentiation, this observation has not been made in the acute CNI rat model. In the latter setting, MSC effects seem to be established by cell recruitment toward the major pelvic ganglion and local paracrine interaction with the host neural tissue.

Conclusions
While the type of model may influence the mechanisms of action of this MSC-based therapy, MSCs generally display efficacy in various animal models for ED. Before translation to the clinic is established, various hurdles need to be overcome.
Clitoral Neuroma After Female Genital Mutilation/Cutting: A Rare but Possible Event
Authors: Abdulcadir Jasmine , Pusztaszeri Marc , Vilarino Raquel , Dubuisson Jean-Bernard , Vlastos Anne-Thérèse 
Published: December 2011

ABSTRACT

Introduction
Female genital mutilation/cutting (FGM/C), in particular, type III, also called infibulation, can cause various long-term complications. However, posttraumatic neuroma of the clitoris is extremely rare; only one case was previously reported in the literature.

Aim
The aim of this study was to describe the case of a patient presenting a clitoral neuroma post-FGM/C in detail and her successful multidisciplinary treatment.

Methods
We report the case of a 24-year-old woman originating from Somalia presenting a type III a–b FGM/C who attended our outpatient clinic at the Geneva University Hospitals complaining of primary dysmenorrhea and a post-mutilation painful clitoral mass. The mass was clinically diagnosed as a cyst and surgically removed. Histopathological analysis revealed that it was a posttraumatic neuroma and a foreign body granuloma around the ancient surgical thread. Our patient was also offered a multidisciplinary counseling by a specialized gynecologist on FGM/C, a sexologist, and a reproductive and sexual health counselor.

Results
One month after surgical treatment, the vulvar pain was over.

Conclusions
This is the second case of clitoral neuroma after FGM/C reported and the first with complete clinical, as well as histopathological documentation and multidisciplinary care. Considering the high frequency of clitoral cysts in case of infibulation, clitoral neuroma should be considered in the differential diagnosis. In this case, if symptomatic, the treatment should be surgery, clinical follow-up, and counseling. If necessary, appropriate sexual therapy should be offered too.
Testing the time‐for‐speciation effect in the assembly of regional biotas
Authors: Rabosky Daniel L. 
Published: December 2011

Summary1. Rates of evolutionary diversification play a fundamental role in the assembly of regional communities, but the relative balance of diversity‐dependent and diversity‐independent rate control remains controversial. Recent studies have reported a significant relationship between the amount of time a geographic region has been occupied and species richness, implying that feedbacks between species interactions and diversification rates may be less important than diversity‐independent mechanisms in generating regional species pools.2. Previous analyses of the regional age‐diversity relationship have used a range of metrics to quantify the amount of ‘evolutionary time’ that a region has been occupied, but the relative performance of these metrics has not been quantified.3. Here, I evaluate the performance of the most commonly used methods and data transformations for assessing the regional age‐diversity relationship.4. I find that process‐based models of diversification are more appropriate than process‐independent models for evaluating the influence of time on species richness. I also demonstrate that time should not be log‐transformed when testing the regional time‐for‐speciation hypothesis, as in some recent studies.5. Application of this framework to patterns of elevational richness in several recent studies provides support for a logistic model of diversity accumulation within elevational bands and implies that evolutionary age alone cannot fully account for current species richness.6. These results indicate that process‐based models, in concert with appropriate data transformation, provide a robust foundation for inference on the causes of regional diversity gradients.
Small Intestinal Intraepithelial Lymphocytes Expressing CD8 and T Cell Receptor γδ Are Involved in Bacterial Clearance during Salmonella enterica Serovar Typhimurium Infection
Authors: Li Zhiyuan , Zhang Cai , Zhou Zhixia , Zhang Jianhua , Zhang Jian , Tian Zhigang 
Published: December 2011

ABSTRACTThe intestinal immune system is crucial for the maintenance of mucosal homeostasis and has evolved under the dual pressure of protecting the host from pathogenic infection and coexisting with the dense and diverse commensal organisms in the lumen. Intestinal intraepithelial lymphocytes (iIELs) are the first element of the host T cell compartment available to respond to oral infection by pathogens. This study demonstrated that oral infection bySalmonella entericaserovar Typhimurium promoted the expansion of iIELs, particularly CD8+TCRγδ+IELs, enhanced expression of NKG2D on iIELs, increased expression of MULT1, and decreased expression of Qa-1 by intestinal epithelial cells (IECs), leading to activation of, particularly, CD8+TCRγδ+iIELs and cytolytic activity againstS. Typhimurium-infected IECs. Blockade of NKG2D recognition or depletion of TCRγδ+cells using a depleting monoclonal antibody significantly attenuated the clearance ofS. Typhimuriumin the intestine and other tissues. This study suggests that iIELs, particularly CD8+TCRγδ+iIELs, play important roles in the detection of pathogenic bacteria and eradication of infected epithelial cells and, thus, provide protection against invading pathogens. These data further our understanding of the mechanisms by which the immune system of the intestinal mucosa discriminates between pathogenic and commensal organisms.
Development and Evaluation of an Ovine Antibody-Based Platform for Treatment of Clostridium difficile Infection
Authors: Roberts April , McGlashan Joanna , Al-Abdulla Ibrahim , Ling Roger , Denton Harriet , Green Steve , Coxon Ruth , Landon John , Shone Clifford 
Published: December 2011

ABSTRACT

Treatment of
Clostridium difficile
is a major problem as a hospital-associated infection which can cause severe, recurrent diarrhea. The currently available antibiotics are not effective in all cases and alternative treatments are required. In the present study, an ovine antibody-based platform for passive immunotherapy of
C. difficile
infection is described. Antibodies with high toxin-neutralizing titers were generated against
C. difficile
toxins A and B and were shown to neutralize three sequence variants of these toxins (toxinotypes) which are prevalent in human
C. difficile
infection. Passive immunization of hamsters with a mixture of toxin A and B antibodies protected them from a challenge with
C. difficile
spores in a dose-dependent manner. Antibodies to both toxins A and B were required for protection. The administration of toxin A and B antibodies up to 24 h postchallenge was found to reduce significantly the onset of
C. difficile
infection compared to nonimmunized controls. Protection from infection was also demonstrated with key disease isolates (ribotypes 027 and 078), which are members of the hypervirulent
C. difficile
clade. The ribotype 027 and 078 strains also have the capacity to produce an active binary toxin and these data suggest that neutralization of this toxin is unnecessary for the management of infection induced by these strains. In summary, the data suggest that ovine toxin A and B antibodies may be effective in the treatment of
C. difficile
infection; their potential use for the management of severe, fulminant cases is discussed.
Acupuncture for Chemotherapy-Induced Peripheral Neuropathy (Cipn): A Pilot Study Using Neurography
Authors: Schroeder Sven , Meyer-Hamme Gesa , Epplée Susanne 
Published: December 2011

Objectives Chemotherapy-induced peripheral neuropathy (CIPN) can produce severe neurological deficits and neuropathic pain and is a potential reason for terminating or suspending chemotherapy treatments. Specific and effective curative treatments are lacking. Methods A pilot study was conducted to evaluate the therapeutic effect of acupuncture on CIPN as measured by changes in nerve conduction studies (NCS) in six patients treated with acupuncture for 10 weeks in addition to best medical care and five control patients who received the best medical care but no specific treatment for CIPN. Results In five of the six patients treated with acupuncture, NCS improved after treatment. In the control group, three of five patients did not show any difference in NCS, one patient improved and one showed impaired NCS. Conclusion The data suggest that acupuncture has a positive effect on CIPN. The encouraging results of this pilot study justify a randomised controlled trial of acupuncture in CIPN on the basis of NCS.
Ontogeny and Astogeny of the Graptolite Genus
Appendispinograptus
(Li and Li, 1985)
Authors: Loxton J. , Melchin M. J. , Mitchell C. E. , Senior S. J. H. 
Published: December 2011

SUMMARY

Graptolites of the genus
Appendispinograptus
feature prominently in Late Ordovician biostratigraphy and studies of biodiversity. Well-documented, but enigmatic, secondary structures extend along the basal spines in mature specimens of three of the four common late Katian species of the genus
: A. supernus, A. longispinus
, and
A. venustus
. Using SEM imaging of isolated, three-dimensional specimens of
A. supernus
, we provide a detailed description of its early growth, as well as confirm that its secondary structures are composed of hollow tubes extending from the sicular and thecal apertures (‘parasiculae’ and ‘parathecae’, respectively). We also describe a collection of Canadian (northern Yukon) appendispinograptids that possess a large heart-shaped, sheet-like basal structure. Detailed comparison (width, thecal length and thecal inclination) with immature specimens from our collection, as well as collections from Russia, China, and Nevada, identifies these specimens as
A. leptothecalis
, a species not previously known to exhibit any secondary spine modification. The observation of spine modification in
A. leptothecalis
allows previously unclassified specimens from China, Siberia, and Nevada to be assigned to this species, clarifying our understanding of appendispinograptid biogeography and diversity. However, these structures are difficult to explain functionally. Unlike structures found in other
Appendispinograptus
species, those in
A. leptothecalis
decrease usable thecal space, shift drag proximally, and provide no obvious feeding advantage.
Monoallelic Expression Determines Oncogenic Progression and Outcome in Benign and Malignant Brain Tumors
Authors: Walker Erin J. , Zhang Cindy , Castelo-Branco Pedro , Hawkins Cynthia , Wilson Wes , Zhukova Nataliya , Alon Noa , Novokmet Ana , Baskin Berivan , Ray Peter , Knobbe Christiane , Dirks Peter , Taylor Michael D. , Croul Sidney , Malkin David , Tabori Uri 
Published: December 2011

Abstract
Although monoallelic expression (MAE) is a frequent genomic event in normal tissues, its role in tumorigenesis remains unclear. Here we carried out single-nucleotide polymorphism arrays on DNA and RNA from a large cohort of pediatric and adult brain tumor tissues to determine the genome-wide rate of MAE, its role in specific cancer-related genes, and the clinical consequences of MAE in brain tumors. We also used targeted genotyping to examine the role of tumor-related genes in brain tumor development and specifically examined the clinical consequences of MAE at TP53 and IDH1. The genome-wide rate of tumor MAE was higher than in previously described normal tissue and increased with specific tumor grade. Oncogenes, but not tumor suppressors, exhibited significantly higher MAE in high-grade compared with low-grade tumors. This method identified nine novel genes highly associated with MAE. Within cancer-related genes, MAE was gene specific; hTERT was most significantly affected, with a higher frequency of MAE in adult and advanced tumors. Clinically, MAE at TP53 exists only in mutated tumors and increases with tumor aggressiveness. MAE toward the normal allele at IDH1 conferred worse survival even in IDH1 mutated tumors. Taken together, our findings suggest that MAE is tumor and gene specific, frequent in brain tumor subtypes, and may be associated with tumor progression/aggressiveness. Further exploration of MAE at relevant genes may contribute to better understanding of tumor development and determine survival in brain tumor patients. Cancer Res; 72(3); 636–44. ©2011 AACR.
Toward the Prognostic Significance and Therapeutic Potential of HER3 Receptor Tyrosine Kinase in Human Colon Cancer
Authors: Beji Abdelhamid , Horst David , Engel Jutta , Kirchner Thomas , Ullrich Axel 
Published: December 2011

Abstract
Purpose: Abnormal accumulation and dysregulation of the epidermal growth factor receptor family member HER3 is associated with the development of various human cancers including those of the breast, lung, and ovary. We have previously shown that in melanoma HER3 is frequently overexpressed and is associated with poor prognosis. However, the importance of HER3 in colon cancer and its putative prognostic significance is still unknown.
Experimental Design: HER3 expression was analyzed in primary colon tumors from 110 patients by immunohistochemistry and correlated with time of progression. Parallel to this, the influence of HER3 overexpression on cell proliferation, migration, invasion, and apoptosis was investigated in four different colon cancer cell lines including DLD-1, LoVo, CaCO2, and T-84.
Results: HER3 was detected at high frequency and exclusively at the membrane of the primary tumors. Elevated HER3 expression levels may serve as a putative prognostic marker because it associates with cell proliferation and decreased time to disease progression. High HER3 protein expression as well as phosphorylation levels were detected in tested cells. HER3 downregulation by RNA interference abrogated cell proliferation, migration, and invasion. In addition, suppression of HER3 resulted in a G2–M cell-cycle arrest, induced apoptosis, and led to morphologic changes in colon cancer cell lines. Furthermore, application of a monoclonal antibody specific to the extracellular portion of the receptor reduced heregulin-β1–induced migration and invasion and also induced apoptosis in colon cancer cell lines.
Conclusion: We postulate that HER3 is critically involved in colon cancer progression and may serve as a novel target for therapeutic intervention. Clin Cancer Res; 18(4); 956–68. ©2011 AACR.
Oncogene Mutation Profiling of Pediatric Solid Tumors Reveals Significant Subsets of Embryonal Rhabdomyosarcoma and Neuroblastoma with Mutated Genes in Growth Signaling Pathways
Authors: Shukla Neerav , Ameur Nabahet , Yilmaz Ismail , Nafa Khedoudja , Lau Chyau-Yueh , Marchetti Angela , Borsu Laetitia , Barr Frederic G. , Ladanyi Marc 
Published: December 2011

Abstract
Purpose: In contrast to the numerous broad screens for oncogene mutations in adult cancers, few such screens have been conducted in pediatric solid tumors. To identify novel mutations and potential therapeutic targets in pediatric cancers, we conducted a high-throughput Sequenom-based analysis in large sets of several major pediatric solid cancers, including neuroblastoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and desmoplastic small round cell tumor (DSRCT).
Experimental Design: We designed a highly multiplexed Sequenom-based assay to interrogate 275 recurrent mutations across 29 genes. Genomic DNA was extracted from 192 neuroblastoma, 75 Ewing sarcoma, 89 RMS, and 24 DSRCT samples. All mutations were verified by Sanger sequencing.
Results: Mutations were identified in 13% of neuroblastoma samples, 4% of Ewing sarcoma samples, 21.1% of RMS samples, and no DSRCT samples. ALK mutations were present in 10.4% of neuroblastoma samples. The remainder of neuroblastoma mutations involved the BRAF, RAS, and MAP2K1 genes and were absent in samples harboring ALK mutations. Mutations were more common in embryonal RMS (ERMS) samples (28.3%) than alveolar RMS (3.5%). In addition to previously identified RAS and FGFR4 mutations, we report for the first time PIK3CA and CTNNB1 (β-catenin) mutations in 5% and 3.3% of ERMS, respectively.
Conclusions: In ERMS, Ewing sarcoma, and neuroblastoma, we identified novel occurrences of several oncogene mutations recognized as drivers in other cancers. Overall, neuroblastoma and ERMS contain significant subsets of cases with nonoverlapping mutated genes in growth signaling pathways. Tumor profiling can identify a subset of pediatric solid tumor patients as candidates for kinase inhibitors or RAS-targeted therapies. Clin Cancer Res; 18(3); 748–57. ©2011 AACR.
Local action of the proinflammatory cytokines IL-1β and IL-6 on intracranial meningeal nociceptors
Authors: Zhang Xichun , Burstein Rami , Levy Dan 
Published: December 2011

Background: Peripheral nociceptive action of the proinflammatory cytokines IL-1β and IL-6 has been implicated in the pathogenesis of numerous pain syndromes. An increase in the level of these cytokines in jugular venous blood has been reported during migraine attacks, suggesting their potential involvement in mediating the intracranial headache of migraine. Methods: In this work we examined, using in vivo single-unit recording of meningeal nociceptors in the trigeminal ganglion of anesthetized rats, whether the peripheral actions of IL-1β and IL-6 can promote the activation and sensitization of nociceptors that innervate the intracranial meninges, two neural processes that are believed to play a key role in promoting the intracranial throbbing pain of migraine. Results: We found that meningeal application of IL-1β leads to the activation and mechanical sensitization of about 70% and 45% of the nociceptors respectively. In contrast, IL-6 was a very poor modulator of meningeal nociceptors’ response properties affecting overall only about 20% of the nociceptors. Conclusions: Our study provides for the first time in vivo electrophysiological evidence that meningeal action of IL-1β can promote the activation and increased mechanosensitivity of intracranial meningeal nociceptors and that IL-6 generally lacks these properties. Future studies are required to examine the mechanism that plays a role in mediating the nociceptive effects of IL-1β on meningeal nociceptors, which may serve as a target for migraine therapy.
Preference, satisfaction and usability of subcutaneously administered methotrexate for rheumatoid arthritis or psoriatic arthritis: results of a postmarketing surveillance study with a high-concentration formulation
Authors: Striesow Frank , Brandt Andreas 
Published: December 2011

Background/objectives: This postmarketing surveillance study assessed the preference, satisfaction, usability, and tolerability of subcutaneous self-administration of a high-concentration (50 mg/ml) ready-to-use formulation of methotrexate (MTX) in patients with rheumatoid arthritis or psoriatic arthritis. Methods: The study enrolled 403 patients with rheumatoid or psoriatic arthritis. The first injection was administered by the attending physician or nurse, followed by five self-administered injections at weekly intervals. The high-concentration formulation consisted of a prefilled syringe with MTX 50 mg/ml solution and a pre-attached needle. Questionnaires were used to document outcomes. Results: The overall assessment was ‘very good’ and ‘good’ in 87.6% of the patients and in 92.8% of the physicians/study nurses. Availability and use of a pre-attached needle was considered as very advantageous and advantageous by 91.8% of the patients and 88.8% of the physicians/study nurses. A total of 96% of the patients described the feeling of the injection as comfortable or tolerable. Patients reported that self-administration led to a feeling of more independence (89.1%) and an improved quality of life (83.6%). A total of 109 patients reported previous self-administration of low-concentration MTX formulations; 94.5% of them stated that they would prefer the high-concentration MTX formulation in the future. The formulation was generally well tolerated. Physicians’ expectations concerning the benefit of switching to MTX self-administration was met in 92.8% of the patients. A total of 96.3% of the patients were considered suitable for subcutaneous self-administration of the MTX formulation. Conclusions: The 50 mg/ml prefilled syringe appears to be a valuable treatment option for patients with rheumatoid and psoriatic arthritis in need of MTX. This is supported by the strong appreciation of the patients as well as their attending healthcare professionals for its convenience and tolerability. The results confirm the findings and experience from a clinical study performed in Germany in 2009, which showed that 93% of the patients prefer the 50 mg/ml prefilled syringe with a pre-attached needle.