bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration
Authors: Kearney H , Rocca MA , Valsasina P , Balk L , Sastre-Garriga J , Reinhardt J , Ruggieri S , Rovira A , Stippich C , Kappos L , Sprenger T , Tortorella P , Rovaris M , Gasperini C , Montalban X , Geurts JJG , Polman CH , Barkhof F , Filippi M , Altmann DR , Ciccarelli O , Miller DH , Chard DT 
Published: June 2013

Background: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. Objectives: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. Methods: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). Results: In the binary model, UCCA ( p < 0.01) and T2LV ( p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA ( p < 0.01), T2LV ( p = 0.02) and GMF ( p = 0.04) were independently associated with disability. Conclusions: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.
Associations of serum fetuin-A levels with insulin resistance and vascular complications in patients with type 2 diabetes
Authors: Jung Chan-Hee , Kim Bo-Yeon , Kim Chul-Hee , Kang Sung-Koo , Jung Sang-Hee , Mok Ji-Oh 
Published: June 2013

Objective: We examined the relationship between serum fetuin-A, insulin resistance (IR), metabolic syndrome (MS) and vascular complications including cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 172 T2DM patients were recruited and evaluated for diabetic microangiopathies (nephropathy, retinopathy and peripheral neuropathy) including CAN. Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay (ELISA), and the IR was assessed by the index of homeostasis model [homeostasis model assessment–insulin resistance (HOMA-IR)]. Atherosclerotic burden was assessed by ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). Results: Serum fetuin-A levels showed significant positive correlations with HOMA-IR (r = 0.196, p = 0.022), and the mean levels of HOMA-IR were significantly increased progressively across fetuin-A tertiles ( p for trend = 0.044). Serum fetuin-A showed significant positive correlations with baPWV, systolic blood pressure (BP), total cholesterol, triglycerides, serum fasting c-peptide and negative correlations with ABI. Serum fetuin-A levels were also negatively correlated with serum adiponectin and positively correlated with serum tumour necrosis factor-α (TNF-α). The mean levels of serum fetuin-A were not significantly different according to the presence of each microangiopathies including CAN. Also, the mean levels of serum fetuin-A were not different between patients with MS and without MS. Conclusions: This present study showed that levels of serum fetuin-A are significantly associated with IR and arterial stiffness assessed by baPWV, while there are no associations with each microangiopathies in patients with T2DM.
The Epilepsy Phenome/Genome Project
Authors:   The EPGP Collaborative, McGovern Kathleen , Stillman Nora , McKenna Kevin , Mays Vickie , Williams Michael , Carpenter Alan , Miller Kevin , Agarwal Prashant , Ayala Jennifer , Bakey Cate , Borkowski Thomas , Boyd Riann , Camuto Alicia , Carrasco Cendy , Cassarly Jennifer , Collins Yong , Collon Kevin , Collon Sean , Eckman Heather , Fogarty Susan , Morón Dolores González , Grayson La June , Hagopian Samantha , Hayden Emily , Heggeli Kristin , Hennessy Rachel , Hessling Jody , Hirschfield Emily , Howell Jennifer , Klingerman Sherry , Lopez Maritza , Marinelli Heather , Maschhaupt Brandy , Minnick Jennie , Misajon Jade , Monahan Jennifer , Oliver Karen , Parulkar Isha , Przepiorka Laura , Pyzik Paula , Regan Brigid , Shain Catherine , Slingerland Lexie , Stanton Caitlin , Taylor Kelly , Thompson Stacy , Turczyk Jennifer , Vara Alexander , Wesolowski Cindy , Yourich Andrew 
Published: July 2013

Background Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype–genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. Results EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. Conclusions EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.
The Total Ankle Arthroplasty Learning Curve With Third-Generation Implants
Authors: Clement R. Carter , Krynetskiy Evgeny , Parekh Selene G. 
Published: June 2013

Background. Renewed interest in total ankle arthroplasty (TAA) has developed globally as a result of recent literature supporting new-generation implants as a viable alternative to arthrodesis. The literature also demonstrates a learning curve among surgeons adopting TAA. The purpose of this study is to better define this learning curve for surgeons using third-generation implants. Methods. Charts and radiographs were reviewed for the initial 26 TAA procedures performed by the senior author. Three third-generation implants were used: SBi (Small Bone Innovations) STAR, Salto Talaris, and Wright Medical INBONE. We report perioperative and early postoperative complications. Results. Two perioperative fractures occurred in the first 9 cases, and the incidence subsequently dropped to 0 ( P = .0431). Two cases of component malalignment occurred in the first 3 patients receiving the STAR implant, and the incidence then dropped to 0 ( P = .0034). Five wound complications (4 minor and 1 major) occurred, all in the final 14 patients. No cases of nerve injury, tendon laceration, or deep vein thrombosis occurred. Two patients returned to the operating room as a result of complications, and the total perioperative and early postoperative complication rate was 27%. Conclusion. The observed rate of perioperative and early postoperative complications in this case series was low relative to other similar-sized studies, suggesting that third-generation implants can reduce adverse events. Our results demonstrate that some common complications could be avoided altogether (nerve/tendon injuries), some decreased quickly with experience (intraoperative fractures and component malpositioning), and some persisted unchanged throughout this study (wound complications). These findings should influence surgical training, surgeon willingness to adopt this procedure, and patient counseling. Levels of Evidence: Therapeutic, Level IV, Retrospective Case Series.
Ultrasound-Guided First Metatarsophalangeal Joint Injections
Authors: Sahler Christopher S. , Spinner David A. , Kirschner Jonathan S. 
Published: June 2013

Objective. To describe a longitudinal ultrasound-guided in-plane approach for injection into the first metatarsophalangeal (MTP) joint and assess its accuracy in a cadaveric model. Design. A prospective anatomical cadaver study model was used. A total of 10 first MTP joints using the described technique were injected with 0.5 mL of dye under ultrasound guidance. The joints were later dissected, and accuracy was classified as accurate, accurate with overflow, or inaccurate with no injectate in the target area. Results. Of the injections, 9 were classified as accurate injections, and 1 was classified accurate with overflow. Conclusion. This cadaveric study suggests that ultrasound-guided injections of the first MTP joint can be accurately and reproducibly performed with a gel standoff, long-axis in-plane approach. This technique attempts to minimize the collateral damage to the surrounding tissue, specifically the articular cartilage. Clinicians should consider using this technique when performing ultrasound-guided injections to the first MTP joint. Level of Evidence: Cadaveric, Level V
Stabbing and safeguarding in children and young people: a Pan-London service evaluation and audit
Authors: Apps John R , Williams Carrie , McGuinness Anne , Gabbie Susie , Sutcliffe Alastair G 
Published: June 2013

Objectives To characterize paediatric presentations of stabbing to emergency departments across London and to audit existing referral rates to the police and social services against the new standard set by the General Medical Council. Design Retrospective multi-centre service evaluation/audit. Setting All emergency departments within London. Participants Patients under 18 years of age presenting to emergency departments with non-accidental stabbing between 1 April 2007 and 30 April 2009. Main outcome measures Patient age, nature of assault, assailant, injuries and management. Rates of documented referral to police and social services, as mandated by GMC guidance. Results A total of 381 presentations were identified from 20 out of the 32 hospitals in London, 160 of whom were less than 16 years old. The majority were seen only by emergency department staff and only a minority (28%) were admitted. Three died in the departments. A knife was the commonest weapon and the limbs the most common site of injury. Referrals to police were documented in only 30% of patients (43% if <16 years old) and to social services in 16% (31% if <16 years old) of those discharged. In the majority, there was no documentation (police 64%, social services 79%). Conclusions A significant number of paediatric stabbings present to emergency departments across London. The majority of these are discharged directly from departments. Of those discharged, documentation regarding referral rates to Police and Social Services was poor, and documented referral rates low. This study covered a period prior to the introduction of new General Medical Council guidance and a repeat audit to assess subsequent documented referrals is required.
Hedgehog inhibition reduces angiogenesis by downregulation of tumoral VEGF‐A expression in hepatocellular carcinoma
Authors: Pinter Matthias , Sieghart Wolfgang , Schmid Monika , Dauser Bernhard , Prager Gerald , Dienes Hans Peter , Trauner Michael , Peck‐Radosavljevic Markus 
Published: June 2013

BackgroundDysregulation and activation of Hedgehog (Hh) signalling may contribute to tumorigenesis, angiogenesis, and metastatic seeding in several solid tumours.ObjectiveWe investigated the impact of Hh inhibition on tumour growth and angiogenesis using in‐vitro and in‐vivo models of hepatocellular carcinoma (HCC).MethodsThe effect of the Hh pathway inhibitor GDC‐0449 on tumour growth was investigated using an orthotopic rat model. Effects on angiogenesis were determined by immunohistochemical staining of von Willebrand factor antigen and by assessing the mRNA expression of several angiogenic factors. In vitro, HCC cell lines were treated with GDC‐0449 and evaluated for viability and expression of vascular endothelial growth factor (VEGF). Endothelial cells were evaluated for viability, migration, and tube formation.ResultsIn the orthotopic HCC model, GDC‐0449 significantly decreased tumoral VEGF expression which was accompanied by a significant reduction of microvessel density and tumour growth. In HCC cells, GDC‐0449 had no effect on cell growth but significantly reduced target gene regulation and VEGF expression while having no direct effect on endothelial cell viability, migration, and tube formation.ConclusionsHh inhibition with GDC‐0449 downregulates tumoral VEGF production in vitro and reduces tumoral VEGF expression, angiogenesis, and tumour growth in an orthotopic HCC model.
Multimodal imaging reveals structural and functional heterogeneity in different bone marrow compartments: functional implications on hematopoietic stem cells
Authors: Lassailly Francois , Foster Katie , Lopez-Onieva Lourdes , Currie Erin , Bonnet Dominique 
Published: June 2013

Key Points
Comparative analysis of epiphyses, diaphyses, and calvaria in terms of homeostatic HSC content, homing, and early reconstitution is described. Noninvasive intravital imaging of intact bones and assessment of BVF, BRA, and hypoxia are reported.
Integrated phosphoproteomic and metabolomic profiling reveals NPM-ALK–mediated phosphorylation of PKM2 and metabolic reprogramming in anaplastic large cell lymphoma
Authors: McDonnell Scott R. P. , Hwang Steven R. , Rolland Delphine , Murga-Zamalloa Carlos , Basrur Venkatesha , Conlon Kevin P. , Fermin Damian , Wolfe Thomas , Raskind Alexander , Ruan Chunhai , Jiang Jian-Kang , Thomas Craig J. , Hogaboam Cory M. , Burant Charles F. , Elenitoba-Johnson Kojo S. J. , Lim Megan S. 
Published: June 2013

Key Points
NPM-ALK induces a metabolic shift toward biomass production. NPM-ALK phosphorylates Y105-PKM2 to regulate metabolism and tumorigenesis.
PPARα and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia
Authors: Tung Stephanie , Shi Yonghong , Wong Karry , Zhu Fang , Gorczynski Reg , Laister Robert C. , Minden Mark , Blechert Anne-Kareen , Genzel Yvonne , Reichl Udo , Spaner David E. 
Published: June 2013

Key Points
Glucocorticoids downregulate PKM2 and metabolism in CLL cells, impairing access to bioenergetic programs needed to repair cell damage. PPARα and fatty acid oxidation antagonists potentiate the cytotoxic effects of glucocorticoids.
Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy
Authors: Jodele Sonata , Licht Christoph , Goebel Jens , Dixon Bradley P. , Zhang Kejian , Sivakumaran Theru A. , Davies Stella M. , Pluthero Fred G. , Lu Lily , Laskin Benjamin L. 
Published: June 2013

Key Points
Genetic variations in the alternative pathway of complement may be associated with thrombotic microangiopathy in children receiving HSCT. These findings may guide the development of novel treatment interventions for this poorly understood transplant complication.
Disruption of rimP-SC, encoding a ribosome assembly cofactor, markedly enhances the production of several antibiotics in Streptomyces coelicolor
Authors: Pan Yuanyuan , Lu Cheng , Dong Hailing , Yu Lingjun , Liu Gang , Tan Huarong 
Published: July 2013

Abstract

Background
Ribosome assembly cofactor RimP is one of the auxiliary proteins required for maturation of the 30S subunit in Escherichia coli. Although RimP in protein synthesis is important, its role in secondary metabolites biosynthesis has not been reported so far. Considering the close relationship between protein synthesis and the production of secondary metabolites, the function of ribosome assembly cofactor RimP on antibiotics production was studied in Streptomyces coelicolor and Streptomyces venezuelae.

Results
In this study, the rimP homologue rimP-SC was identified and cloned from Streptomyces coelicolor. Disruption of rimP-SC led to enhanced production of actinorhodin and calcium-dependent antibiotics by promoting the transcription of act II-ORF4 and cdaR. Further experiments demonstrated that MetK was one of the reasons for the increment of antibiotics production. In addition, rimP-SC disruption mutant could be used as a host to produce more peptidyl nucleoside antibiotics (polyoxin or nikkomycin) than the wild-type strain. Likewise, disruption of rimP-SV of Streptomyces venezuelae also significantly stimulated jadomycin production, suggesting that enhanced antibiotics production might be widespread in many other Streptomyces species.

Conclusion
These results established an important relationship between ribosome assembly cofactor and secondary metabolites biosynthesis and provided an approach for yield improvement of secondary metabolites in Streptomyces.
Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells
Authors: Sun Jin-ping , Shi Zhen-yu , Liu Shi-meng , Kang Yu-hua , Hu Guo-qiang , Huangfu Chao-shen , Deng Jin-bo , Liu Bin 
Published: July 2013

Abstract

Background
In order to search for new structural modification strategies on fluoroquinolones, we have designed and synthesized a series of fluoroquinolone derivatives by linking various hydrazine compounds to the C-3 carboxyl group of levofloxacin and assessed their anticancer activities. Several novel levofloxacin derivatives displayed potent cytotoxicity against the tested cancer cell lines in vitro. In the present study, we investigated the effect of 1-Cyclopropyl-6-fluoro-4-oxo-7- piperazin-1, 4-dihydro- quinoline- 3-carboxylic acid benzo [1,3] dioxol-5- ylmethylene- hydrazide (QNT11) on the apoptosis of human hepatocarcinoma cells in vitro.

Methods
The inhibition effects of QNT11 on cell proliferation were examined by MTT assay. Cell apoptosis was determined by TUNEL and DNA agarose gel electrophoresis method. The topoisomerase ΙΙ activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Cell cycle progression was analyzed using flow cytometry in conjunction with ethanol fixation and propidium iodide staining. Mitochondrial membrane potential (△ψm) was measured by high content screening image system. The caspase-9, caspase-8, caspase-3, Bcl-2, Bax, CDK1, Cyclin B1and cytochrome c protein expressions were detected by Western blot analysis.

Results
QNT11 showed selective cytotoxicity against Hep3B, SMMC-7721, MCF-7 and HCT-8 cell lines with IC50 values of 2.21 μM, 2.38 μM, 3.17 μM and 2.79 μM, respectively. In contrast, QNT11 had weak cytotoxicity against mouse bone marrow mesenchymal stem cells (BMSCs) with IC50 value of 7.46 μM. Treatment of Hep3B cells with different concentrations of QNT11 increased the percentage of the apoptosis cells significantly, and agarose gel electrophoresis revealed the ladder DNA bands typical of apoptotic cells, with a decrease in the mitochondrial membrane potential. Compared to the control group, QNT11 could influence the DNA topoisomerase IIactivity and inhibit the religation of DNA strands, thus keeping the DNA in fragments. There was a significant increase of cytochrome c in the cytosol after 24 h of treatment with QNT11 and a decrease in the mitochondrial compartment. Observed changes in cell cycle distribution by QNT11 treated might be caused by insufficient preparation for G2/M transition. In addition, QNT11 increased the protein expression of Bax, caspase-9, caspase-8, caspase-3, as well as the cleaved activated forms of caspase-9, caspase-8 and caspase-3 significantly, whereas the expression of Bcl-2 decreased.

Conclusions
Our results showed that QNT11 as a fluoroquinolone derivative exerted potent and selectively anticancer activity through the mechanism of eukaryotic topoisomerase II poisoning. The growth inhibition was in large part mediated via apoptosis-associated mitochondrial dysfunction and regulation of Bcl-2 signaling pathways.
Feasibility and safety study of a new device (Odón device) for assisted vaginal deliveries: study protocol
Authors:   The World Health Organization Odon Device Research Group
Published: July 2013

Abstract

Background
Intrapartum complications are responsible for approximately half of all maternal deaths, and two million stillbirth and neonatal deaths per year. Prolonged second stage of labour is associated with potentially fatal maternal complications such as haemorrhage and infection and it is a major cause of stillbirth and newborn morbidity and mortality. Currently, the three main options for managing prolonged second stage of labour are forceps, vacuum extractor and caesarean section. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for caesarean section) and/or highly trained staff which are often not available in low resource settings. The specific aim of the proposed study is to test the safety and feasibility of a new device (Odón device) to effectively deliver the fetus during prolonged second stage of labour. The Odón device is a low-cost technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care and reducing maternal and perinatal morbidity and mortality in low resource settings.

Methods/design
This will be a hospital-based, multicenter prospective phase 1 cohort study with no control group. Delivery with the Odón device will be attempted under normal labour and non-emergency conditions on all the women enrolled in the study. One-hundred and thirty pregnant women will be recruited in tertiary care facilities in Argentina. Safety will be assessed by examining maternal and infant outcomes until discharge. Feasibility will be evaluated by observing successful expulsion of the fetal head after one-time application of the device under standardized conditions (full cervical dilation, anterior presentation, +2 station, normal fetal heart rate).

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier:ACTRN12613000141741