bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phospholipase C gamma mediates endogenous brain-derived neurotrophic factor-regulated calcitonin gene-related peptide expression in colitis-induced visceral pain
Authors: Hashmi Fiza , Liu Miao , Shen Shanwei , Qiao Li-Ya 
Published: June 2016

Background Visceral hypersensitivity is a complex pathophysiological paradigm with unclear mechanisms. Primary afferent neuronal plasticity marked by alterations in neuroactive compounds such as calcitonin gene-related peptide is suggested to underlie the heightened sensory responses. Signal transduction that leads to calcitonin gene-related peptide expression thereby sensory neuroplasticity during colitis remains to be elucidated. Results In a rat model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid, we found that endogenously elevated brain-derived neurotrophic factor elicited an up-regulation of calcitonin gene-related peptide in the lumbar L1 dorsal root ganglia. At seven days of colitis, neutralization of brain-derived neurotrophic factor with a specific brain-derived neurotrophic factor antibody reversed calcitonin gene-related peptide up-regulation in the dorsal root ganglia. Colitis-induced calcitonin gene-related peptide transcription was also inhibited by brain-derived neurotrophic factor antibody treatment. Signal transduction studies with dorsal root ganglia explants showed that brain-derived neurotrophic factor-induced calcitonin gene-related peptide expression was mediated by the phospholipase C gamma, but not the phosphatidylinositol 3-kinase/Akt or the mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathway. Application of PLC inhibitor U73122 in vivo confirmed that colitis-induced and brain-derived neurotrophic factor-mediated calcitonin gene-related peptide up-regulation in the dorsal root ganglia was regulated by the phospholipase C gamma pathway. In contrast, suppression of the phosphatidylinositol 3-kinase activity in vivo had no effect on colitis-induced calcitonin gene-related peptide expression. During colitis, calcitonin gene-related peptide also co-expressed with phospholipase C gamma but not with p-Akt. Calcitonin gene-related peptide up-regulation during colitis correlated to the activation of cAMP-responsive element binding protein in the same neurons. Consistently, colitis-induced cAMP-responsive element binding protein activation in the dorsal root ganglia was attenuated by brain-derived neurotrophic factor antibody treatment. Conclusion These results suggest that colitis-induced and brain-derived neurotrophic factor-mediated calcitonin gene-related peptide expression in sensory activation is regulated by a unique pathway involving brain-derived neurotrophic factor-phospholipase C gamma-cAMP-responsive element binding protein axis.
Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats
Authors: Xu Jing , Wang Wei , Zhong Xiong-Xiong , Feng Yi-Wei , Wei Xu-Hong , Liu Xian-Guo 
Published: June 2016

Background Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. Results We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve. Moreover, in the spinal dorsal horn, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the protein expression of p-p65 as well as tumor necrosis factor α was increased, whereas the protein expression of IL-10 was decreased following vincristine treatment. Furthermore, intraperitoneal injection of methylcobalamin could dose dependently attenuate vincristine-induced mechanical allodynia and thermal hyperalgesia, which was associated with intraepidermal nerve fibers rescue, and atypical mitochondria prevalence decrease in the sciatic nerve. Moreover, methylcobalamin inhibited the activation of NADPH oxidase and the downstream NF-κB pathway. Production of tumor necrosis factor α was also decreased and production of IL-10 was increased in the spinal dorsal horn following methylcobalamin treatment. Intrathecal injection of Phorbol-12-Myristate-13-Acetate, a NADPH oxidase activator, could completely block the analgesic effect of methylcobalamin. Conclusions Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-κB pathway, resulting in the rebalancing of proinflammatory and anti-inflammatory cytokines in the spinal dorsal horn might also be involved. These findings might provide potential target for preventing vincristine-induced neuropathic pain.
Use of routinely collected data in reporting falls in hospitals in a local health district in New South Wales, Australia
Authors: Trinh Lieu Thi Thuy , Achat Helen , Assareh Hassan 
Published: June 2016

Objective: To examine the quality of the two routinely collected sets of data, the Incident Information Management System (IIMS) and the health information exchange (HIE) in hospitals in New South Wales, Australia. Method: IIMS records indicating a fall and its location were examined. HIE data were examined using International Classification of Diseases (ICD)-10-AM codes W00-W19 and an indicator, ‘onset of the condition’ for falls in hospital. If onset of the condition was not recorded, ICD-10-AM code for place of occurrence (Y92.22 = Health service area) immediately following ICD-10-AM code for the fall was used. Comprehensive criteria were applied to exclude records of earlier documented falls. IIMS and HIE data were linked. Characteristics of falls that were recorded in one data set but not in the other were determined. Results: Between January 2010 and December 2014, 8647 falls in hospitals were recorded in IIMS, 2169 were recorded in HIE and 9338 were recorded in either data set (rate of 3.2 falls per 1000 bed days). IIMS captured 93% and HIE captured 23% of these falls. Of the falls recorded in HIE, 677 (31%) were not recorded in IIMS. These were more likely to be subsequent falls, by patients who were female, younger than 65 years, who underwent a non-allied health procedure or had length of stay less than 1 week. Conclusions: IIMS captured the vast majority of falls in hospitals but failed to report one-third of falls recorded in HIE.
Institutional Registry of Elderly Patients With Hip Fracture in a Community-Based Tertiary Care Hospital in Argentina (RIAFC)
Authors: Benchimol Javier , Fiorentini Fernando , Elizondo Cristina M. , Boietti Bruno R. , Carabelli Guido , Barla Jorge , Sancineto Carlos , Waisman Gabriel D. , Giunta Diego H. 
Published: June 2016

Background: A clinical registry encompasses a selective set of rigorously collected and stored clinical data focused on a specific condition. Hip fracture is a common complication of osteoporosis in elderly patients. Hip fracture substantially increases the risk of death and major morbidity in the elderly patients. Limited data regarding hip fracture are available from Latin America and Argentina. The purpose of this project is to create an institutional registry of elderly patients with hip fracture in order to obtain data that reveal the impact of this disease in our environment, allowing us to evaluate different strategies of patient’s care and clinical outcomes. Objective: To describe the implementation of an institutional registry of elderly patients with hip fracture in Argentina. Methods: In this article, we described the creation, implementation, and data management of a prospective registry of elderly patients with hip fracture. The registry contains information on baseline demographics, comorbidities, laboratory, and radiological data. Follow-up at 3 and 12 months postfracture is done by phone interview to assess physical function, readmissions, and morbi-mortality. Clinical Trials registry number NCT02279550. Conclusion: In this project, we have created a hip fracture registry. We hope that this registry will provide valuable data that can lead us to new lines of research, addressed to answer questions raised in clinical practice.
LARS Artificial Ligament Versus ABC Purely Polyester Ligament for Anterior Cruciate Ligament Reconstruction
Authors: Iliadis Dimitrios Ph. , Bourlos Dimitrios N. , Mastrokalos Dimitrios S. , Chronopoulos Efstathios , Babis George C. 
Published: June 2016

Background: Graft choice for anterior cruciate ligament (ACL) reconstruction is of critical importance. Various grafts have been used so far, with autografts long considered the optimal solution for the treatment of ACL-deficient knees. Limited data are available on the long-term survivorship of synthetic grafts. Purpose: To compare the functional outcome and survivorship of ACL reconstructions performed using the LARS (ligament augmentation and reconstruction system) ligament and the ABC (active biosynthetic composite) purely polyester ligament. Study Design: Case series; Level of evidence, 4. Methods: The results of 72 patients who underwent primary arthroscopic ACL reconstruction with the LARS ligament and 31 cases with an ABC purely polyester ligament were reviewed. The mean follow-up periods for the LARS and ABC groups were 9.5 and 5.1 years, respectively. A survivorship analysis of the 2 synthetic grafts was performed using the Kaplan-Meier method with a log-rank test (Mantel-Cox, 95% CI). Lysholm, Tegner activity, Knee injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) scores as well as laxity measurements obtained using a KT-1000 arthrometer were recorded for all intact grafts, and a Mann-Whitney U test was used for comparison reasons. Results: The rupture rates for LARS and ABC grafts were 31% (95% CI, 20%-42%) and 42% (95% CI, 25%-59%), respectively. For intact grafts, the mean Lysholm score was good for both groups (90 for the LARS group and 89 for the ABC group), with the majority of patients returning to their preinjury level of activities, and the mean IKDC score was 90 for the LARS group and 86 for the ABC group. Conclusion: The rupture rates of both LARS and ABC grafts were both high. However, the LARS ligament provided significantly better survivorship compared with the ABC ligament at short- to midterm follow-up (95% CI).
CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma
Authors: Nijhof Inger S. , Casneuf Tineke , van Velzen Jeroen , van Kessel Berris , Axel Amy E. , Syed Khaja , Groen Richard W. J. , van Duin Mark , Sonneveld Pieter , Minnema Monique C. , Zweegman Sonja , Chiu Christopher , Bloem Andries C. , Mutis Tuna , Lokhorst Henk M. , Sasser A. Kate , van de Donk Niels W. C. J. 
Published: June 2016

Key Points
Response to the CD38-targeting antibody daratumumab is significantly associated with CD38 expression levels on the tumor cells. Resistance to daratumumab is accompanied by increased expression of complement-inhibitory proteins.
Long-term safety and tolerability of bapineuzumab in patients with Alzheimer’s disease in two phase 3 extension studies
Authors: Ivanoiu Adrian , Pariente Jérémie , Booth Kevin , Lobello Kasia , Luscan Gerald , Hua Lisa , Lucas Prisca , Styren Scot , Yang Lingfeng , Li David , Black Ronald S. , Brashear H. Robert , McRae Thomas 
Published: June 2016

Abstract
Background
Immunotherapy with monoclonal antibodies that target amyloid beta has been under investigation as a treatment for patients with Alzheimer’s disease (AD). The 3000 and 3001 phase 3 clinical studies of intravenous bapineuzumab assessed safety and efficacy in patients with mild to moderate AD recruited in over 26 countries. This article describes the long-term safety and tolerability of bapineuzumab in the extension studies for these two protocols.

Methods
The long-term safety and tolerability of intravenous-administered bapineuzumab in patients with AD was evaluated in apolipoprotein E ε4 allele noncarriers (Study 3002, extension of Study 3000) and apolipoprotein E ε4 allele carriers (Study 3003, extension of Study 3001). Those receiving bapineuzumab in the parent study were continued at the same dose; if receiving placebo, patients began bapineuzumab. Bapineuzumab doses were 0.5 mg/kg in both studies and also 1.0 mg/kg in the noncarrier study. Clinical efficacy of bapineuzumab was also assessed in exploratory analyses.

Results
Because of lack of efficacy in two other phase 3 trials, the parent protocols were stopped early. As a result, Studies 3002 and 3003 were also terminated. In total, 492 and 202 patients were enrolled in Studies 3003 and 3002, respectively. In apolipoprotein E ε4 carriers (Study 3003), treatment-emergent adverse events occurred in 70.7 % of the patients who originally received placebo and 66.9 % of those who originally received bapineuzumab. In noncarriers, treatment-emergent adverse events occurred in 82.1 % and 67.6 % of patients who received placebo + bapineuzumab 0.5 mg/kg and placebo + bapineuzumab 1.0 mg/kg, respectively, and in 72.7 % and 64.3 % of those who received bapineuzumab + bapineuzumab 0.5 mg/kg and 1.0 mg/kg, respectively. Amyloid-related imaging abnormalities with edema or effusions were the main bapineuzumab-associated adverse events in both studies, occurring in approximately 11 % of placebo + bapineuzumab and 4 % of bapineuzumab + bapineuzumab groups overall. Exploratory analyses of clinical efficacy were not significantly different between groups in either study.

Conclusions
In these phase 3 extension studies, intravenous bapineuzumab administered for up to approximately 3 years showed no unexpected safety signals and a safety profile consistent with previous bapineuzumab trials.

Trial registration
Noncarriers (Study 3002): ClinicalTrials.gov NCT00996918. Registered 14 October 2009.
Carriers (Study 3003): ClinicalTrials.gov NCT00998764. Registered 16 October 2009.
Challenges of Treating Childhood Medulloblastoma in a Country With Limited Resources: 20 Years of Experience at a Single Tertiary Center in Malaysia
Authors: Rajagopal Revathi , Abd-Ghafar Sayyidatul , Ganesan Dharmendra , Bustam Mainudin Anita Zarina , Wong Kum Thong , Ramli Norlisah , Jawin Vida , Lum Su Han , Yap Tsiao Yi , Bouffet Eric , Qaddoumi Ibrahim , Krishnan Shekhar , Ariffin Hany , Abdullah Wan Ariffin 
Published: June 2016

Purpose Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. Methods Fifty-one patients with childhood MB were seen at University Malaya Medical Center. Data from 43 patients were analyzed; eight patients were excluded because their families refused treatment after surgery. Results Headache and vomiting were the most common presenting symptoms, and the mean interval between symptom onset and diagnosis was 4 weeks. Fourteen patients presented with metastatic disease. Five-year progression-free survival (± SE) for patients ≥ 3 years old was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) in the high-risk group and 68.6% ± 18.6% (95% CI, 40.3% to 100%) in the average-risk group, and 5-year overall survival (± SE) in these two groups was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) and 58.3% ± 18.6% (95% CI, 31.3% to 100%), respectively. Children younger than 3 years old had 5-year progression-free and overall survival rates (± SE) of 47.6% ± 12.1% (95% CI, 28.9% to 78.4%) and 45.6% ± 11.7% (95% CI, 27.6% to 75.5%), respectively. Time to relapse ranged from 4 to 132 months. Most patients who experienced relapse died within 1 year. Febrile neutropenia, hearing loss, and endocrinopathy were the most common treatment-related complications. Conclusion The survival rate of childhood MB in Malaysia is inferior to that usually reported in the literature. We postulate that the following factors contribute to this difference: lack of a multidisciplinary neuro-oncology team, limited health care facilities, inconsistent risk assessment, insufficient data in the National Cancer Registry and pathology reports, inadequate long-term follow-up, and cultural beliefs leading to treatment abandonment.
The extraordinary joint material of an articulated coralline alga. I. Mechanical characterization of a key adaptation
Authors: Denny Mark W. , King Felicia A. 
Published: June 2016

ABSTRACT
Flexibility is key to survival for seaweeds exposed to the extreme hydrodynamic environment of wave-washed rocky shores. This poses a problem for coralline algae, whose calcified cell walls make them rigid. Through the course of evolution, erect coralline algae have solved this problem by incorporating joints (genicula) into their morphology, allowing their fronds to be as flexible as those of uncalcified seaweeds. To provide the flexibility required by this structural innovation, the joint material of Calliarthron cheilosporioides, a representative articulated coralline alga, relies on an extraordinary tissue that is stronger, more extensible and more fatigue resistant than the tissue of other algal fronds. Here, we report on experiments that reveal the viscoelastic properties of this material. On the one hand, its compliance is independent of the rate of deformation across a wide range of deformation rates, a characteristic of elastic solids. This deformation rate independence allows joints to maintain their flexibility when loaded by the unpredictable – and often rapidly imposed – hydrodynamic force of breaking waves. On the other hand, the genicular material has viscous characteristics that similarly augment its function. The genicular material dissipates much of the energy absorbed as a joint is deformed during cyclic wave loading, which potentially reduces the chance of failure by fatigue, and the material accrues a limited amount of deformation through time. This limited creep increases the flexibility of the joints while preventing them from gradually stretching to the point of failure. These new findings provide the basis for understanding how the microscale architecture of genicular cell walls results in the adaptive mechanical properties of coralline algal joints.
DOCLASP - Docking ligands to target proteins using spatial and electrostatic congruence extracted from a known holoenzyme and applying simple geometrical transformations
Authors: Chakraborty Sandeep 
Published: June 2016

The ability to accurately and effectively predict the interaction between proteins and small drug-like compounds has long intrigued researchers for pedagogic, humanitarian and economic reasons. Protein docking methods (AutoDock, GOLD, DOCK, FlexX and Glide to name a few) rank a large number of possible conformations of protein-ligand complexes using fast algorithms. Previously, it has been shown that structural congruence leading to the same enzymatic function necessitates the congruence of electrostatic properties (CLASP). The current work presents a methodology for docking a ligand into a target protein, provided that there is at least one known holoenzyme with ligand bound - DOCLASP (Docking using CLASP). The contact points of the ligand in the holoenzyme defines a motif, which is used to query the target enzyme using CLASP. If there are significant matches, the holoenzyme and the target protein are superimposed based on congruent atoms. The same linear and rotational transformations are also applied to the ligand, thus creating a unified coordinate framework having the holoenzyme, the ligand and the target enzyme. In the current work, the dipeptidyl peptidase-IV inhibitor vildagliptin was docked to the PI-PLC structure complexed with myo-inositol using DOCLASP. Also, corroboration of the docking of phenylthiourea to the modelled structure of polyphenol oxidase (JrPPO1) from walnut is provided based on the subsequently solved structure of JrPPO1 (PDBid:5CE9). Analysis of the binding of the antitrypanosomial drug suramin to nine non-homologous proteins in the PDB database shows a diverse set of binding motifs, and multiple binding sites in the phospholipase A2-likeproteins from the Bothrops genus of pitvipers. The conformational changes in the suramin molecule on binding highlights the challenges in docking flexible ligands into an already ’plastic’ binding site. Thus, DOCLASP presents a method for ’soft docking’ ligands to proteins with low computational requirements.
New types of cultural tourism as a tool for developing the tourism potential of the city of Krasnoyarsk
Authors: Бекетова Наталья , Beketova Natalya , Бутова Татьяна , Butova Tatyana , Черняева Алена , Chernyaeva Alena 
Published: June 2016

The article discusses the growth prospects of tourist flow in Krasnoyarsk, by means of the transformation of city&#180;s transit destination into independent tourist site due to the holding there XXIX International winter Universiade 2019. Ensuring the growth of tourist flow by means of tourism conversion of the main participants in sports events, i.e. the transformation of a latent and potential consumers of tourism services into tourists, actualizes the problem of development of city tourist potential. Desk research has revealed the interest in sight-seeing tours in their free time. If the sportsmen will get the satisfaction from excursions and tours across Krasnoyarsk, they will desire to revisit the city as a tourist and recommend this city to friends and family as a tourist object.
The technology of assessment of the city’s tourism potential and innovation of urban tourism are the subject of the study. Within the estimation of use of Krasnoyarsk‘s tourist potential a comparative analysis of the city image before and after the organized and unorganized trekking tourism has been conducted, which allowed to identify the problem of accurate positioning of Krasnoyarsk as a tourist destination. Comparative analysis of offers tourism products of Krasnoyarsk and demand in them revealed the problem of low level knowledge of tourism products, but also allowed to establish the fact that tourist resources exceed city’s touristic potential.
The practical problem of the growth of Krasnoyarsk’s tourist potential through innovation caused the need for solution of theoretical problems, in particular, clarifying the classification of cultural tourism. Monitoring the development of new forms of cultural products, the cultural space in particular, has shown promise for their development as tourist attractions.
Functional analysis of new types of cultural products in Krasnoyarsk such as cultural space &#34;Kamenka&#34; and the historic quarter are subject to urban cultural tourism, enhancing the city’s tourist potential. Thus the development of the innovation in cultural tourism will lead to the expansion of the offer of new tourist attractions of Krasnoyarsk and will make it an independent tourist destination.