bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidural analgesia provides effective pain relief in patients undergoing open liver surgery
Authors: Ganapathi Senthil , Roberts Gemma , Mogford Susan , Bahlmann Barbara , Ateleanu Bazil , Kumar Nagappan 
Published: March 2014

Background: Epidural analgesia has been the reference standard for the provision of post-operative pain relief in patients recovering from major upper abdominal operations, including liver resections. However, a failure rate of 20–32% has been reported. Aim: The aim of the study was to analyse the success rates of epidural analgesia and the outcome in patients who underwent liver surgery. Methods: We collected data from a prospectively maintained database of 70 patients who underwent open liver surgery by a bilateral subcostal incision during a period of 20 months (February 2009 to September 2010). Anaesthetic consultants with expertise in anaesthesia for liver surgery performed the epidural catheter placement. A dedicated pain team assessed the post-operative pain scores on moving or coughing using the Verbal Descriptor Scale. The outcome was measured in terms of epidural success rates, pain scores, post-operative chest infection and length of hospital stay. Results: The study group included 43 males and 27 females. The indication for resection was liver secondaries (70%), primary tumours (19%) and benign disease (11%). While major (≥3 segments) and minor resections (≤ 2 segments) were performed in 44% and 47% respectively, 9% of patients were inoperable. Epidural analgesia was successful in 64 patients (91%). Bacterial colonisation of epidural tip was noticed in two patients. However, no neurological complications were encountered. Five patients (7%) had radiologically confirmed chest infection. Four patients (6%) developed wound infection. One patient died due to liver failure following extended right hepatectomy and cholecystectomy for gall bladder cancer. The median length of stay was 6 days (3–27 days). The extent of liver resection (p = 0.026) and post-operative chest infection (p = 0.012) had a significant influence on the length of stay. Conclusion: Our experience shows that epidural analgesia is safe and effective in providing adequate pain relief following open liver surgery.
Time and Cost of Diagnosis for Symptomatic Femoroacetabular Impingement
Authors: Kahlenberg Cynthia A. , Han Brian , Patel Ronak M. , Deshmane Prashant P. , Terry Michael A. 
Published: March 2014

Background: Femoroacetabular impingement (FAI) and labral tears are common causes of hip pain that are often not promptly or properly diagnosed. To our knowledge, no reports have defined the time and cost of diagnosis of labral tears associated with FAI. Hypothesis: Patients with labral tears associated with FAI undergo extraneous diagnostic testing and pain and incur a significant amount of health care costs before they receive appropriate surgical management for their pathology. Study Design: Economic and decision analysis; Level of evidence, 4. Methods: A total of 78 patients diagnosed with symptomatic FAI were surveyed. A standardized questionnaire asked patients about time to diagnosis, symptoms, health care providers visited, imaging tests, and treatments prior to diagnosis. Costs were calculated based on 2012 national Medicare data. Results: Patients in the cohort saw an average of 4.0 health care providers, had an average of 3.4 diagnostic imaging tests, and tried an average of 3.1 treatments prior to diagnosis. The average total amount spent per patient prior to diagnosis was US$2456.97. The calculated minimum cost of diagnosis, including a visit to an orthopaedic surgeon as well as an anteroposterior pelvis and lateral hip radiograph and 1 magnetic resonance arthrogram, was US$690.62. The average duration between onset of symptoms and diagnosis of labral tear was 32.0 months. Conclusion: The average amount of health care dollars spent per patient prior to receiving a diagnosis of acetabular labral tear was US$1766.35 higher than the calculated minimum cost. This figure is based on Medicare payment amounts, which may significantly underestimate the actual charges at many hospitals, thereby increasing the total cost of diagnosis. Clinical Relevance: The costs and pain associated with this time, along with the potential long-term degradation of the hip joint, make it important for all health care professionals to recognize and appropriately manage or refer the patient.
A novel tescalcin-sodium/hydrogen exchange axis underlying sorafenib resistance in FLT3-ITD+ AML
Authors: Man Cheuk Him , Lam Stephen S. Y. , Sun Murphy K. H. , Chow Howard C. H. , Gill Harinder , Kwong Yok Lam , Leung Anskar Y. H. 
Published: March 2014

Key PointsA novel TESC-NEH1 pathway is involved in FLT3-ITD+ AML pathogenesis. Inhibition of NHE1 overcomes sorafenib resistance in FLT3-ITD+AML.
Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia
Authors: Brown Jennifer R. , Byrd John C. , Coutre Steven E. , Benson Don M. , Flinn Ian W. , Wagner-Johnston Nina D. , Spurgeon Stephen E. , Kahl Brad S. , Bello Celeste , Webb Heather K. , Johnson Dave M. , Peterman Sissy , Li Daniel , Jahn Thomas M. , Lannutti Brian J. , Ulrich Roger G. , Yu Albert S. , Miller Langdon L. , Furman Richard R. 
Published: March 2014

Key PointsIdelalisib was evaluated in 54 patients with heavily pretreated chronic lymphocytic leukemia, and target inhibition was documented in vivo. Oral idelalisib therapy demonstrated a favorable safety profile and rapidly induced durable disease control in the majority of patients.
Atypical Listeria innocua strains possess an intact LIPI-3
Authors: Clayton Evelyn M , Daly Karen M , Guinane Caitriona M , Hill Colin , Cotter Paul D , Ross Paul R 
Published: March 2014

Abstract

Background

Listeria monocytogenes is a food-borne pathogen which is the causative agent of listeriosis and can be divided into three evolutionary lineages I, II and III. While all strains possess the well established virulence factors associated with the Listeria pathogenicity island I (LIPI-1), lineage I strains also possess an additional pathogenicity island designated LIPI-3 which encodes listeriolysin S (LLS), a post-translationally modified cytolytic peptide. Up until now, this pathogenicity island has been identified exclusively in a subset of lineage I isolates of the pathogen Listeria monocytogenes.

Results
In total 64 L. innocua strains were screened for the presence of LIPI-3. Here we report the identification of an intact LIPI-3 in 11 isolates of L. innocua and the remnants of the cluster in several others. Significantly, we can reveal that placing the L. innocua lls genes under the control of a constitutive promoter results in a haemolytic phenotype, confirming that the cluster is capable of encoding a functional haemolysin.

Conclusions
Although the presence of the LIPI-3 gene cluster is confined to lineage I isolates of L. monocytogenes, a corresponding gene cluster or its remnants have been identified in many L. innocua strains.
Neuroprotection by rAAV-mediated gene transfer of bone morphogenic protein 7
Authors: Heinonen Ann-Marie , Rahman Mahbubur , Dogbevia Godwin , Jakobi Hannah , Wölfl Stefan , Sprengel Rolf , Schwaninger Markus 
Published: March 2014

Abstract

Background
Bone morphogenic proteins (BMPs) promote the survival of neurons, suggesting a therapeutic application of BMPs in the treatment of acute and chronic neurodegenerative disorders. However, the application of recombinant BMPs in vivo is limited by their short half-life. To provide a continuous supply for functionally active BMPs, we expressed BMP7, BMP2 and the BMP inhibitor Noggin under the control of rAAV vectors in vivo. For visual control of rAAV-mediated BMP (v-BMP) expression we fused the secreted morphogenic polypeptides and the fluorescent reporter protein Venus via the ‘ribosomal skip’ promoting 2A peptide-bridge.

Results
In primary cortical neurons, the rAAV-expressed morphogenic polypeptides were efficiently released from the 2A-Venus fusion precursors, were secreted, correctly processed and functionally active as shown by their effects on Smad phosphorylation in HeLa cells and in primary neurons, by the protection of v-BMP7-transduced primary cortical neurons against oxidative stress, and by the activation of BMP responsive GFP in v-BMP2 transduced reporter mice. In the stroke model of middle cerebral artery occlusion rAAV-transduced v-BMP7 reduced the infarct size in mice.

Conclusion
Polycistronic rAAV vectors encoding secreted polypeptides and 2A-linked reporter proteins are potential novel therapeutic tools for the treatment of neurological and neurodegenerative diseases. Using this technique we documented that rAAV delivery of BMP7 reduced ischemic cell death in mice.
Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease
Authors: Mochalski Paweł , King Julian , Haas Matthias , Unterkofler Karl , Amann Anton , Mayer Gert 
Published: March 2014

Abstract

Background
Monitoring of volatile organic compounds (VOCs) in exhaled breath shows great potential as a non-invasive method for assessing hemodialysis efficiency. In this work we aim at identifying and quantifying of a wide range of VOCs characterizing uremic breath and blood, with a particular focus on species responding to the dialysis treatment.

Methods
Gas chromatography with mass spectrometric detection coupled with solid-phase microextraction as pre-concentration method.

Results
A total of 60 VOCs were reliably identified and quantified in blood and breath of CKD patients. Excluding contaminants, six compounds (isoprene, dimethyl sulfide, methyl propyl sulfide, allyl methyl sulfide, thiophene and benzene) changed their blood and breath levels during the hemodialysis treatment.

Conclusions
Uremic breath and blood patterns were found to be notably affected by the contaminants from the extracorporeal circuits and hospital room air. Consequently, patient exposure to a wide spectrum of volatile species (hydrocarbons, aldehydes, ketones, aromatics, heterocyclic compounds) is expected during hemodialysis. Whereas highly volatile pollutants were relatively quickly removed from blood by exhalation, more soluble ones were retained and contributed to the uremic syndrome. At least two of the species observed (cyclohexanone and 2-propenal) are uremic toxins. Perhaps other volatile substances reported within this study may be toxic and have negative impact on human body functions. Further studies are required to investigate if VOCs responding to HD treatment could be used as markers for monitoring hemodialysis efficiency.
Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma
Authors: Tsuchiya Norihiko , Yuasa Takeshi , Maita Shinya , Narita Shintaro , Inoue Takamitsu , Numakura Kazuyuki , Saito Mitsuru , Satoh Shigeru , Yonese Junji , Habuchi Tomonori 
Published: March 2014

AbstractBackgroundTyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib.MethodsPatients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter.ResultsA total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm.ConclusionsPatients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.
Childhood abuse is associated with methylation of multiple loci in adult DNA
Authors: Suderman Matthew , Borghol Nada , Pappas Jane J , Pinto Pereira Snehal M , Pembrey Marcus , Hertzman Clyde , Power Chris , Szyf Moshe 
Published: March 2014

AbstractBackgroundChildhood abuse is associated with increased adult disease risk, suggesting that processes acting over the long-term, such as epigenetic regulation of gene activity, may be involved. DNA methylation is a critical mechanism in epigenetic regulation. We aimed to establish whether childhood abuse was associated with adult DNA methylation profiles.MethodsIn 40 males from the 1958 British Birth Cohort we compared genome-wide promoter DNA methylation in blood taken at 45y for those with, versus those without, childhood abuse (n = 12 vs 28). We analysed the promoter methylation of over 20,000 genes and 489 microRNAs, using MeDIP (methylated DNA immunoprecipitation) in triplicate.ResultsWe found 997 differentially methylated gene promoters (311 hypermethylated and 686 hypomethylated) in association with childhood abuse and these promoters were enriched for genes involved in key cell signaling pathways related to transcriptional regulation and development. Using bisulfite-pyrosequencing, abuse-associated methylation (MeDIP) at the metalloproteinase gene,PM20D1, was validated and then replicated in an additional 27 males. Abuse-associated methylation was observed in 39 microRNAs; in 6 of these, the hypermethylated state was consistent with the hypomethylation of their downstream gene targets. Although distributed across the genome, the differentially methylated promoters associated with child abuse clustered in genome regions of at least one megabase. The observations for child abuse showed little overlap with methylation patterns associated with socioeconomic position.ConclusionsOur observed genome-wide methylation profiles in adult DNA associated with childhood abuse justify the further exploration of epigenetic regulation as a mediating mechanism for long-term health outcomes.
Lack of validation of genetic variants associated with anti–tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis
Authors: Márquez Ana , Ferreiro-Iglesias Aida , Dávila-Fajardo Cristina L , Montes Ariana , Pascual-Salcedo Dora , Perez-Pampin Eva , Moreno-Ramos Manuel J , García-Portales Rosa , Navarro Federico , Moreira Virginia , Magro César , Caliz Rafael , Ferrer Miguel Angel , Alegre-Sancho Juan José , Joven Beatriz , Carreira Patricia , Balsa Alejandro , Vasilopoulos Yiannis , Sarafidou Theologia , Cabeza-Barrera José , Narvaez Javier , Raya Enrique , Cañete Juan D , Fernández-Nebro Antonio , Ordóñez María del Carmen , de la Serna Arturo R , Magallares Berta , Gomez-Reino Juan J , González Antonio , Martín Javier 
Published: March 2014

Abstract
Introduction
In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations.

Methods
The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients.

Results
None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis.

Conclusion
Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.
Percutaneous dilatational tracheostomy: mostly safe, but do benefits outweigh risks?
Authors: Scales Damon C , Cuthbertson Brian H 
Published: March 2014

AbstractPercutaneous dilatational tracheostomies have become one of the most frequently performed surgical procedures in the ICU, and are believed to offer a variety of advantages over open tracheostomies, including increased convenience. Recent publications have established that the risk of fatal complications related to the procedure is low. However, clinicians must still weigh these risks against expected but largely unproven benefits. More research is needed to establish the indications for the procedure, including the optimal patient selection and timing during a course of mechanical ventilation. Such studies should also seek to improve our ability to accurately identify which patients will require prolonged mechanical ventilation, and to quantify the potential benefits of tracheostomy compared with prolonged translaryngeal intubation.
Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells
Authors: Martin Rebecca K , Saleem Sheinei J , Folgosa Lauren , Zellner Hannah B , Damle Sheela R , Nguyen Giang-Kim T , Ryan John J , Bear Harry D , Irani Anne-Marie , Conrad Daniel H 
Published: March 2014

ABSTRACTIt has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate that the lack of MCs also influences MDSC trafficking. Preferential trafficking to the liver was not seen in MC-deficient mice. In addition, evidence that the MC mediator histamine was important in MDSC trafficking and activation is also shown. MDSCs express HR1–3. Blockade of these receptors by HR1 or HR2 antagonists reversed the histamine enhancement of MDSC survival and proliferation observed in cell culture. In addition, histamine differentially influenced Arg1 and iNOS gene expression in MDSCs and greatly enhanced IL-4 and IL-13 message, especially in granulocytic MDSCs. Evidence that histamine influenced activity seen in vitro translated to in vivo when HR1 and HR2 antagonists blocked the effect of MDSCs on parasite expulsion and tumor metastasis. All of these data support the MDSC-mediated promotion of Th2 immunity, leading to the suggestion that allergic-prone individuals would have elevated MDSC levels. This was directly demonstrated by looking at the relative MDSC levels in allergic versus control patients. Monocytic MDSCs trended higher, whereas granulocytic MDSCs were increased significantly in allergic patients. Taken together, our studies indicate that MCs and MC-released histamine are critical for MDSC-mediated immune regulation, and this interaction should be taken into consideration for therapeutic interventions that target MDSCs.
Cesium Adsorption by Synthetic Todorokite-Type Manganese Oxides
Authors: Chitrakar Ramesh , Makita Yoji , Sonoda Akinari 
Published: March 2014

Abstract
Synthetic todorokite-type manganese oxides containing magnesium (todorokite(Mg)), calcium (todorokite(Ca)), and iron-doped todorokite containing magnesium (Fe-todorokite(Mg)) were treated with acid solutions to obtain protonated todorokite(Mg-H), todorokite(Ca-H), and Fe-todorokite(Mg-H), respectively, and studied for cesium adsorption from the aqueous solutions. The cesium adsorption rate was slow to attain equilibrium in 24 h at pH 4.4–5.5 (uncontrolled); the adsorptive capacities were 0.50 mmol g−1 for todorokite(Mg-H), 0.49 mmol g−1 for todorokite(Ca-H), and 0.27 mmol g−1 for Fe-todorokite(Mg-H). The cesium adsorptive capacity was significantly dependent on pH, increasing with increase in pH. A partial substitution of Mn by Fe (7.2 wt %) in the framework of todorokite greatly decreased the cesium adsorptive capacity compared to metal-undoped todorokite. The distribution coefficient Kd values of the protonated materials for Na+, K+, Cs+, Mg2+, and Ca2+ at 1.0 mmol dm−3 in acidic pH showed that the materials preferred Cs+ over other cations. Both todorokite(Mg-H) and todorokite(Ca-H) were effective for cesium adsorption completely (ca. 100%) from drinking water intentionally contaminated with 0.1 mmol dm−3 CsCl at solution-to-solid ratio of 0.1–1.0 dm3 g−1.
Quantitative Assessment of Mutant Allele Burden in Solid Tumors by Semiconductor-Based Next-Generation Sequencing
Authors: Portier Bryce P. , Kanagal-Shamanna Rashmi , Luthra Rajyalakshmi , Singh Rajesh , Routbort Mark J. , Handal Brian , Reddy Neelima , Barkoh Bedia A. , Zuo Zhuang , Medeiros L. Jeffrey , Aldape Kenneth , Patel Keyur P. 
Published: March 2014

Abstract

Objectives:
Identification of tumor-specific somatic mutations has had a significant impact on both disease diagnosis and therapy selection. The ability of next-generation sequencing (NGS) to provide a quantitative assessment of mutant allele burden, in numerous target genes in a single assay, provides a significant advantage over conventional qualitative genotyping platforms.

Methods:
We assessed the quantitative capability of NGS and a primer extension–based matrix-assisted laser desorption ionization–time-of-flight (PE-MALDI) assay and directly correlated NGS mutant allele burden determination to morphologic assessment of tumor percentage in H&E-stained slides.

Results:
Our results show a 100% concordance between NGS and PE-MALDI in mutant allele detection and a significant correlation between NGS and PE-MALDI for determining mutant allele burden when mutant allele burden is 10% or more.

Conclusions:
NGS-based mutation screening provides a quantitative assessment comparable to that of PE-MALDI. In addition, NGS also allows for a high degree of multiplexing and uses nanogram quantities of DNA, thereby preserving precious material for future analysis. Furthermore, this study provides evidence that H&E-based morphologic assessment of tumor burden does not correlate to actual tumor mutant allele burden frequency.