bluuebunny/crossref_metadata_2025_split huggingface dataset:
The New Zealand serious non-fatal self-harm indicators: how valid are they for monitoring trends?
Authors: Gulliver Pauline , Cryer Colin , Davie Gabrielle 
Published: November 2011

BackgroundTo monitor accurately injury incidence trends, indicators should measure incidence independently of extraneous factors. Frequencies and rates of New Zealand's serious non-fatal self-harm indicators may be prone to fluctuations in reporting owing, for example, to changing social norms. Hence, they have been considered provisional.AimTo validate empirically the serious non-fatal self-harm indicators.MethodsAll serious non-fatal first admissions to hospital were identified and classified according to whether principal diagnosis (PDx) was injury or mental disorder, and conversely whether contributing diagnoses were mental disorder or injury. The proportion assigned self-harm external cause of injury code (E-code) was calculated for each year from 2001 to 2007. Subsequently, all cases with a self-harm E-code were identified, and the proportion with a PDx of injury and contributing diagnosis of mental disorder, or PDx of mental disorder and contributing diagnosis of injury over time, were determined.ResultsNo linear changes over time were detected in the proportion of cases assigned an injury PDx, or the proportion assigned a mental disorder PDx, or the proportion with a self-harm E-code. The estimated maximum observed increase in the frequency of serious non-fatal self-harm hospitalisation explained by changes in reporting was 19– 40%.ConclusionIdentification of serious non-fatal self-harm events using an operational definition of PDx of injury, a self-harm first listed E-code, and an appropriate severity cut-off point, is a valid method of monitoring incidence and rates in New Zealand.
Making the message meaningful: a qualitative assessment of media promoting all-terrain vehicle safety
Authors: Brann Maria , Mullins Samantha Hope , Miller Beverly K , Eoff Shane , Graham James , Aitken Mary E 
Published: November 2011

BackgroundMillions of all-terrain vehicles (ATV) are used around the world for recreation by both adults and youth. This increase in use has led to a substantial increase in the number of injuries and fatalities each year. Effective strategies for reducing this incidence are clearly needed; however, minimal research exists regarding effective educational interventions.ObjectiveThis study was designed to assess rural ATV riders' preferences for and assessment of safety messages.Methods13 focus group discussions with youth and adult ATV riders were conducted. 88 formative research participants provided feedback on existing ATV safety materials, which was used to develop more useful ATV safety messages. 60 evaluative focus group participants critiqued the materials developed for this project.ResultsExisting ATV safety materials have limited effectiveness, in part because they may not address the content or design needs of the target population. ATV riders want educational and action-oriented safety messages that inform youth and adult riders about their responsibilities to learn, educate and implement safety behaviours (eg, appropriate-sized ATV, safety gear, solo riding, speed limits, riding locations). In addition, messages should be clear, realistic, visually appealing and easily accessible. Newly designed ATV safety materials using the acronym TRIPSS (training, ride off-road, impairment, plan ahead, safety gear, single rider) meet ATV riders' safety messaging needs.ConclusionsTo reach a target population, it is crucial to include them in the development and assessment of safety messages. Germane to this particular study, ATV riders provided essential information for creating useful ATV safety materials.
Tumor Suppressive MicroRNAs miR-34a/c Control Cancer Cell Expression of ULBP2, a Stress-Induced Ligand of the Natural Killer Cell Receptor NKG2D
Authors: Heinemann Anja , Zhao Fang , Pechlivanis Sonali , Eberle Jürgen , Steinle Alexander , Diederichs Sven , Schadendorf Dirk , Paschen Annette 
Published: November 2011

Abstract
Malignant cells express ligands for the natural killer cell immunoreceptor NKG2D, which sensitizes to early recognition and elimination by cytotoxic lymphocytes and provides an innate barrier against tumor development. However, the mechanisms that control NKG2D ligand (NKG2DL) expression in tumor cells remain unknown. We recently identified the NKG2DL ULBP2 as strong prognostic marker in human malignant melanoma. Here, we provide evidence that the tumor-suppressive microRNAs (miRNA) miR-34a and miR-34c control ULBP2 expression. Reporter gene analyses revealed that both miRNAs directly targeted the 3′-untranslated region of ULBP2 mRNA and that levels of miR-34a inversely correlated with expression of ULBP2 surface molecules. Accordingly, treatment of cancer cells with miRNA inhibitors led to upregulation of ULBP2, whereas miR-34 mimics led to downregulation of ULBP2, diminishing tumor cell recognition by NK cells. Treatment with the small molecule inhibitor Nutlin-3a also decreased ULBP2 levels in a p53-dependent manner, which was due to a p53-mediated increase in cellular miR-34 levels. Taken together, our study shows that tumor-suppressive miR-34a and miR-34c act as ULBP2 repressors. These findings also implicate p53 in ULBP2 regulation, emphasizing the role of the specific NKG2DL in tumor immune surveillance. Cancer Res; 72(2); 460–71. ©2011 AACR.
HMGB1 Promotes Drug Resistance in Osteosarcoma
Authors: Huang Jun , Ni Jiangdong , Liu Ke , Yu Yan , Xie Min , Kang Rui , Vernon Philip , Cao Lizhi , Tang Daolin 
Published: November 2011

Abstract
Osteosarcoma is the most commonly occurring bone cancer in children and adolescents. Unfortunately, treatment failures are common due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. In this study, we implicate the DNA-binding protein HMGB1, which also exerts immunoregulatory effects in its secreted form, in the development of drug resistance in osteosarcoma. Anticancer agents including doxorubicin, cisplatin, and methotrexate each induced HMGB1 upregulation in human osteosarcoma cells, and RNA interference–mediated knockdown of HMGB1 restored the chemosensitivity of osteosarcoma cells in vivo and in vitro. Mechanistic investigation revealed that HMGB1 increased drug resistance by inducing autophagy, an intracellular self-defense mechanism known to confer drug resistance. We found that HMGB1 bound to the autophagy regulator Beclin1 and regulated the formation of the Beclin1–PI3KC3 [PI3KC3, phosphatidylinositol 3-kinase class 3] complex that facilitates autophagic progression. In addition, we found that interaction between HMGB1 and Beclin1 relied upon the autophagic complex ULK1–mAtg13–FIP200. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance, and it offers a novel target for improving osteosarcoma therapy. Cancer Res; 72(1); 230–8. ©2011 AACR.
An Anti-Wnt5a Antibody Suppresses Metastasis of Gastric Cancer Cells In Vivo by Inhibiting Receptor-Mediated Endocytosis
Authors: Hanaki Hideaki , Yamamoto Hideki , Sakane Hiroshi , Matsumoto Shinji , Ohdan Hideki , Sato Akira , Kikuchi Akira 
Published: November 2011

Abstract
Wnt5a is a representative ligand that activates the β-catenin–independent pathway in Wnt signaling. It was reported that the expression of Wnt5a in human gastric cancer is associated with aggressiveness and poor prognosis and that knockdown of Wnt5a reduces the ability of gastric cancer cells to metastasize in nude mice. Therefore, Wnt5a and its signaling pathway might be important targets for the therapy of gastric cancer. The aim of this study was to examine whether an anti-Wnt5a antibody affects metastasis of gastric cancer cells. One anti-Wnt5a polyclonal antibody (pAb5a-5) inhibited migration and invasion activities in vitro of gastric cancer cells with a high expression level of Wnt5a. Previously, it was shown that Wnt5a induces the internalization of receptors, which is required for Wnt5a-dependent activation of Rac1. pAb5a-5 inhibited Wnt5a-dependent internalization of receptors, thereby suppressed Wnt5a-dependent activation of Rac1. Laminin γ2 is one of target genes of Wnt5a signaling and Rac1 was involved in its expression. pAb5a-5 also inhibited Wnt5a-dependent expression of laminin γ2. In an experimental liver metastasis assay, gastric cancer cells were introduced into the spleens of nude mice. Laminin γ2 was required for liver metastatic ability of gastric cancer cells in vivo. Furthermore, intraperitoneal injection of pAb5a-5 inhibited the metastatic ability of gastric cancer cells. These results suggest that an anti-Wnt5a antibody was capable of suppressing Wnt5a-dependent internalization of receptors, resulting in the prevention of metastasis of gastric cancer cells by inhibiting the activation of Rac1 and the expression of laminin γ2. Mol Cancer Ther; 11(2); 298–307. ©2011 AACR.
Short-Term Biomarker Modulation Prevention Study of Anastrozole in Women at Increased Risk for Second Primary Breast Cancer
Authors: Arun Banu , Valero Vicente , Liu Diane , Brewster Abenaa , Green Marjorie , Gutierrez-Barrera Angelica , Akar Ugur , Rivera Edgardo , Esteva Francisco J. , Buzdar Aman U. , Hortobagyi Gabriel N. , Sneige Nour 
Published: November 2011

Abstract
The selective estrogen receptor modulators (SERM), Tamoxifen and raloxifen reduce risk breast cancer. Patient acceptance of SERMs for breast cancer prevention is low due to toxicities. New agents with a better toxicity profile are needed. Aromatase inhibitors (AI) reduce the risk of contralateral breast cancer and risk of new breast cancer in high risk women. However, the mechanism by which AIs reduce breast risk is not known. Surrogate biomarkers are needed to evaluate the effect of preventive agents. The objective of this prospective short-term prevention study was to evaluate the effect of anastrozole on biomarkers in breast tissue and serum of women at increased risk for developing a contralateral breast cancer. Women with a history of stage I, II breast cancer who started anastrozole for standard adjuvant treatment were eligible. Patients underwent baseline fine needle aspiration of the unaffected breast and serum collection for biomarker analysis before starting anastrozole at 1 mg per oral/day and again at 6 months. Biomarkers included changes in cytology, insulin-like growth factor 1 (IGF-1), IGF-binding protein 1 (IGFBP-1), and IGFBP-3. Thirty-seven patients were enrolled. There was a significant modulation in serum IGFBP-1 levels between pre- and postsamples (P = 0.02). No change was observed in IGF-1, IGFBP-3, and breast cytology.We showed a significant modulation of IGFBP-1 levels with six months anastrozole. Anastrozole is currently being studied as a prevention agent in a large phase III trial and our results provide support for continued evaluation of IGFBP-1 as a surrogate endpoint biomarker in prospective breast chemoprevention studies. Cancer Prev Res; 5(2); 276–82. ©2011 AACR.
Ototoxicity of Intratympanic Docusate Sodium and Mineral Oil in the Guinea Pig
Authors: Nader Marc‐Elie , Saliba Issam 
Published: November 2011

Objectives(1) To evaluate the ototoxic potential of docusate sodium and mineral oil and (2) to compare the cerumenolytic properties of these agents to water and a commercially available product.Study DesignProspective animal study.SettingDocusate sodium and mineral oil are being used to dissolve cerumen plugs. Their ototoxicity has never been assessed.MethodsNineteen guinea pigs represented 38 ears, which formed 4 groups. Each group was injected with an intratympanic solution once a week for 4 weeks. Group 1 was injected with a negative control solution of saline, group 2 with docusate sodium, group 3 with a positive control solution of gentamicin, and group 4 with mineral oil. Auditory brainstem responses (ABRs) were recorded before any procedure and 1 week after the final injections. Cochleas were analyzed under scanning electron microscopy. The cerumenolytic properties of water, docusate sodium, mineral oil, and cerumol were evaluated.ResultsThere was no significant ABR threshold increase for saline or mineral oil. Gentamicin and docusate sodium caused a significant threshold increase that averaged 51.9 dB and 44.9 dB over all the frequencies (P <. 001). Electron microscopy could not be performed on the cochleas treated by docusate sodium because of very severe osteitis. All of the agents tested seemed to be effective cerumenolytics compared with no treatment, but water was significantly more effective compared with any of the other tested products (P <. 001).ConclusionDocusate sodium was severely ototoxic, and its use should be discouraged. Mineral oil was not ototoxic. Water seemed to be the most effective cerumenolytic agent.
Prevalence, Characteristics, and Management of Swallowing Disorders following Cerebellopontine Angle Surgery
Authors: Starmer Heather M. , Best Simon R. , Agrawal Yuri , Chien Wade W. , Hillel Alexander T. , Francis Howard W. , Tamargo Rafael J. , Akst Lee M. 
Published: November 2011

ObjectiveTo describe swallowing disorders encountered after cerebellopontine angle surgery and to explore variables associated with increased incidence of postoperative dysphagia.Study DesignCase series with chart review.SettingSingle academic medical institution.Subjects and MethodsChart review of 181 consecutive patients undergoing surgical excision of cerebellopontine angle pathology from January 2008 to December 2010 at the Johns Hopkins Hospital. Presence and characteristics of dysphagia were determined by review of speech pathologist reports. Other clinical variables were extracted from the electronic medical record, and statistical analyses were applied to determine factors associated with postoperative dysphagia.ResultsImmediate postoperative dysphagia was identified in 57 of 181 patients (31%). Oral, oropharyngeal, and pharyngeal deficits accounted for 51%, 37%, and 12% of dysphagic symptoms, respectively. Facial nerve weakness in the immediate postoperative period was noted in 91% of dysphagic subjects compared with 43% of those without. Mean House‐Brackmann score for dysphagic individuals was 4 compared with 2 in the nondysphagic group. Diet alterations were required for 65% of dysphagic individuals, and an additional 9% required tube feeding. Common findings during videofluoroscopic swallowing studies were pharyngeal residue, reduced pharyngeal constriction, and anterior bolus loss. Abnormal penetration‐aspiration scores (≥3) were found in 59% of those undergoing videofluoroscopic swallow studies.ConclusionsOral and pharyngeal swallowing deficits are commonly encountered after cerebellopontine angle surgery. Consultation with the speech‐language pathologist appears most critical for any individuals demonstrating postoperative cranial nerve dysfunction, particularly for those with evidence of facial nerve weakness. Early consultation may help to manage short‐ and long‐term functional difficulties.
Intratympanic Treatment of Intractable Unilateral Ménière Disease
Authors: Casani Augusto Pietro , Piaggi Paolo , Cerchiai Niccolò , Seccia Veronica , Sellari Franceschini Stefano , Dallan Iacopo 
Published: November 2011

ObjectiveTo determine the efficacy and safety of low‐dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable unilateral Ménière disease (MD).Study DesignOpen prospective randomized controlled study.SettingTertiary referral center.Subjects and MethodsSixty patients affected by definite unilateral MD were enrolled between January 1, 2007, and June 30, 2008. Thirty‐two patients were treated with a buffered gentamicin solution injected in the middle ear (maximum of 2 injections); 28 patients were treated with ITD (4 mg/mL, 3 injections at intervals of 1 every 3 days). Mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), speech discrimination score, functional disability score, and statistical analysis using repeated measures analysis of variance.ResultsIn the ITG group at 2‐year follow‐up, complete control of vertigo (class A) was achieved in 26 patients (81%) and substantial control of vertigo (class B) in 4 patients (12.5%). In the ITD group, class A was achieved in 12 (43%), and class B in 5 (18%) patients. In the gentamicin group, 4 patients showed a reduction in PTA of ≥10 dB. In the ITD group, PTA was unchanged or slightly improved in 16 patients (belonging to class A‐B) and worse in 12.ConclusionsLow‐dose ITG achieved better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral MD, with a very low incidence of hearing deterioration. ITD offers poorer vertigo control rate, and hearing preservation is achieved only in cases with no vertigo recurrences.
Profile of an American Amateur Rugby Union Sevens Series
Authors: Lopez Victor , Galano Gregory J. , Black Christopher M. , Gupta Arun T. , James Douglas E. , Kelleher Kristen M. , Allen Answorth A. 
Published: November 2011

Background: Rugby union will enter the Olympic arena as Rugby Sevens in 2016. Purpose: To investigate the injury rate, injury type, and nature of injuries sustained in an amateur American rugby union sevens tournament series. Study Design: Descriptive epidemiology study. Methods: The rate, demographics, and characteristics of injury were evaluated in 1536 rugby union sevens players, from 128 sides, competing in 4 amateur 1-day tournaments in a USA Rugby local area rugby union. Results: Forty-eight injuries occurred over 4 tournaments, for an injury rate of 55.4 injuries per 1000 playing hours. Head and neck injuries were most common (33.3% of injuries), followed by upper extremity (31.3%), trunk (18.8%), lower extremity (14.6%), and physiologic injuries (2.1%). The most common type of injury was ligament sprain (25.0%); followed by concussion (14.6%), hematoma/contusion (12.5%), muscle strain (10.4%), and abrasion (8.3%). Tackling was the most common mechanism of injury (74.5%). Males were injured at a significantly higher rate than females (RR, 7.5, P < .01), but no significant difference was observed based on player position ( P = .08). Conclusion: Injuries are common among American amateur rugby athletes, with a substantial proportion involving the head and neck region. Clinical Relevance: Understanding injury patterns in an American rugby union will be important for formulating future injury prevention, assessment, and treatment protocols.
The principal results of the International Immune Tolerance Study: a randomized dose comparison
Authors: Hay Charles R. M. , DiMichele Donna M. 
Published: November 2011

AbstractThe International Immune Tolerance Study was a multicenter, prospective, randomized comparison of high-dose (HD; 200 IU/kg/d) and low-dose (LD; 50 IU/kg 3 times/week) factor VIII regimens in 115 “good-risk,” severe high-titer inhibitor hemophilia A subjects. Sixty-six of 115 subjects reached the defined study end points: success, n = 46 (69.7%); partial response, n = 3 (4.5%); and failure, n = 17 (25.8%). Successes did not differ between treatment arms (24 of 58 LD vs 22/57 HD, P = .909). The times taken to achieve a negative titer (P = .027), a normal recovery (P = .002), and tolerance (P = .116, nonsignificant) were shorter with the HD immune tolerance induction (ITI). Peak historical (P = .026) and on-ITI (P = .002) titers were correlated inversely with success, but only peak titer on ITI predicted outcome in a multivariate analysis (P = .002). LD subjects bled more often (odds ratio, 2.2; P = .0019). The early bleed rate/month was 0.62 (LD) and 0.28 (HD; P = .000 24), decreasing by 90% once negative titers were achieved. Bleeding was absent in 8 of 58 LD versus 21 of 57 HD subjects (P = .0085). One hundred twenty-four central catheter infections were reported in 41 subjects (19 LD); infection frequency did not differ between the treatment arms. Neither bleeding nor infection influenced outcome. Although it was stopped early for futility and safety considerations, this trial contributed valuable data toward evidence-based ITI practice.
SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells
Authors: Lai Yu-Heng , Cheng Jessica , Cheng Dongmei , Feasel Mattie E , Beste Kyle D , Peng Junmin , Nusrat Asma , Moreno Carlos S 
Published: November 2011

AbstractBackgroundSOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression.ResultsHere, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such asAXIN2,DICER1, andDHX9. In addition, SOX4 DNA binding activity to the promoters ofDICER1,AXIN2,DHX9andSOX4itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4-plakoglobin interactions resulted in reduced transcriptional activity of β-catenin luciferase reporters.ConclusionsThese data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression.