bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ghrelin inhibits LPS-induced release of IL-6 from mouse dopaminergic neurones
Authors: Beynon Amy L , Brown M Rowan , Wright Rhiannon , Rees Mark I , Sheldon I Martin , Davies Jeffrey S 
Published: March 2013

Abstract

Background
Ghrelin is an orexigenic stomach hormone that acts centrally to increase mid-brain dopamine neurone activity, amplify dopamine signaling and protect against neurotoxin-induced dopamine cell death in the mouse substantia nigra pars compacta (SNpc). In addition, ghrelin inhibits the lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines from peripheral macrophages, T-cells and from LPS stimulated microglia. Here we sought to determine whether ghrelin attenuates pro-inflammatory cytokine release from dopaminergic neurones.

Findings
The dopaminergic SN4741 cell-line, which derives from the mouse substantia nigra (SN) and expresses the ghrelin-receptor (growth hormone secretagogue receptor (GHS-R)) and the ghrelin-O-acyl transferase (GOAT) enzyme, was used to determine the neuro-immunomodulatory action of ghrelin. We induced innate immune activation via LPS challenge (1 μg/ml) of SN4741 neurones that had been pre-cultured in the presence or absence of ghrelin (1, 10, 100 nM) for 4 h. After 24 h supernatants were collected for detection of IL-1 beta (IL-1β ), TNF alpha (TNF-α) and IL-6 cytokines via enzyme linked immunosorbent assay (ELISA) analysis. Nuclear translocation of the transcription factor nuclear factor kappa B (NF-κB) was analyzed by Western blotting, and to determine viability of treatments a cell viability assay and caspase-3 immunohistochemistry were performed.
We provide evidence that while IL-1β and TNF-α were not detectable under any conditions, SN4741 neurones constitutively released IL-6 under basal conditions and treatment with LPS significantly increased IL-6 secretion. Pre-treatment of neurones with ghrelin attenuated LPS-mediated IL-6 release at 24 h, an affect that was inhibited by the GHS-R antagonist [D-Lys3]-GHRP-6. However, while ghrelin pre-treatment attenuated the LPS-mediated increase in NF-κB, there was no alteration in its nuclear translocation. Cell viability assay and caspase-3 immunocytochemistry demonstrated that the results were independent from activation of cytotoxic and/or apoptotic mechanisms in the neuronal population, respectively.

Conclusion
Our results provide evidence that the gut-hormone, ghrelin, attenuates IL-6 secretion to LPS challenge in mid-brain dopaminergic neurones. These data suggest that ghrelin may protect against dopaminergic SN nerve cell damage or death via modulation of the innate immune response.
Predictors of poor outcome after both column acetabular fractures: a 30-year retrospective cohort study
Authors: Lichte Philipp , Sellei Richard M , Kobbe Philipp , Dombroski Derek G , Gänsslen Axel , Pape Hans-Christoph 
Published: March 2013

AbstractBackground and PurposeAcetabular fractures are often combined with associated injuries to the hip joint. Some of these associated injuries seem to be responsible for poor long-term results and these injuries seem to affect the outcome independent of the quality of the acetabular reduction. The aim of our study was to analyze the outcome of both column acetabular fractures and the influence of osseous cofactors such as initial fracture displacement, hip dislocation, femoral head lesions and injuries of the acetabular joint surface.MethodsA retrospective cohort study in patients with both column acetabular fractures treated over a 30 year period was performed. Patients with a follow-up of more than two years were invited for a clinical and radiological examination. Displacement was analyzed on initial and postoperative radiographs. Contusion and impaction of the femoral head was grouped. Injuries of the acetabular joint surface consisting of impaction, contusion and comminution were recorded. The Merle d’Aubigné Score was documented and radiographs were analysed for arthritis (Helfet classification), femoral head avascular necrosis (Ficat/Arlet classification) and heterotopic ossifications (Brooker classification).Results115 patients were included in the follow up examination. Anatomic reduction (malreduction ≤ 1mm) was associated with a significantly better clinical outcome than nonanatomical reduction (p = 0.001). Initial displacement of more than 10mm (p = 0.031) and initial intraarticular fragments (p = 0.041) were associated with worse outcome. Other associated injuries, such as the presence of a femoral head dislocation, femoral head injuries and injuries to the acetabular joint surface showed no significant difference in outcome individually, but in fractures with more than two associated local injuries the risk for joint degeneration was significant higher (p < 0.001) than in cases with less than two of them.In the subgroup of anatomically reconstructed fractures no significant influence of the analyzed cofactors could be observed.ConclusionAnatomical reduction appears to be an important parameter for a good clinical outcome in patients with both column acetabular fractures. Additional fracture characteristics such as the initial displacement and intraarticular fragments seem to influence the results. Patients should also be advised that both column acetabular fractures with more than two additional associated factors have a significantly higher risk of joint degeneration.
The effect of diabetes mellitus on the association between measures of glycaemiccontrol and ICU mortality: a retrospective cohort study
Authors: Sechterberger Marjolein K , Bosman Robert J , Oudemans-van Straaten Heleen M , Siegelaar Sarah E , Hermanides Jeroen , Hoekstra Joost BL , De Vries J Hans 
Published: March 2013

Abstract
Introduction
In critical illness, four measures of glycaemic control are associated with ICUmortality: mean glucose concentration, glucose variability, the incidence ofhypoglycaemia (≤ 2.2 mmol/l) or low glucose (2.3 to 4.7 mmol/l). Underlyingdiabetes mellitus (DM) might affect these associations. Our objective was to studywhether the association between these measures of glycaemic control and ICUmortality differs between patients without and with DM and to explore the cutoffvalue for detrimental low glucose in both cohorts.

Methods
This retrospective database cohort study included patients admitted betweenJanuary 2004 and June 2011 to a 24-bed medical/surgical ICU in a teachinghospital. We analysed glucose and outcome data from 10,320 patients: 8,682 withoutDM and 1,638 with DM. The cohorts were subdivided into quintiles of mean glucoseand quartiles of glucose variability. Multivariable regression models were used toexamine the independent association between the four measures of glycaemic controland ICU mortality, and for defining the cutoff value for detrimental lowglucose.

Results
Regarding mean glucose, a U-shaped relation was observed in the non-DM cohort withan increased ICU mortality in the lowest and highest glucose quintiles (odds ratio= 1.4 and 1.8, P < 0.001). No clear pattern was found in the DMcohort. Glucose variability was related to ICU mortality only in the non-DMcohort, with highest ICU mortality in the upper variability quartile (odds ratio =1.7, P < 0.001). Hypoglycaemia was associated with ICU mortality inboth cohorts (odds ratio non-DM = 2.5, P < 0.001; odds ratio DM = 4.2,P = 0.001), while low-glucose concentrations up to 4.9 mmol/l wereassociated with an increased risk of ICU mortality in the non-DM cohort and up to3.5 mmol/l in the DM cohort.

Conclusion
Mean glucose and high glucose variability are related to ICU mortality in thenon-DM cohort but not in the DM cohort. Hypoglycaemia (≤ 2.2 mmol/l) wasassociated with ICU mortality in both. The cutoff value for detrimental lowglucose is higher in the non-DM cohort (4.9 mmol/l) than in the DM cohort (3.5mmol/l). While hypoglycaemia (≤ 2.2 mmol/l) should be avoided in bothgroups, DM patients seem to tolerate a wider glucose range than non-DMpatients.
Personal genome testing in medical education: student experiences with genotyping in the classroom
Authors: Vernez Simone Lucia , Salari Keyan , Ormond Kelly E , Lee Sandra Soo-Jin 
Published: March 2013

Abstract
Background
Direct-to-consumer (DTC) personal genotyping services are beginning to be adoptedby educational institutions as pedagogical tools for learning about humangenetics. However, there is little known about student reactions to such testing.This study investigated student experiences and attitudes towards DTC personalgenome testing.

Methods
Individual interviews were conducted with students who chose to undergo personalgenotyping in the context of an elective genetics course. Ten medical and graduatestudents were interviewed before genotyping occurred, and at 2 weeks and 6 monthsafter receiving their genotype results. Qualitative analysis of interviewtranscripts assessed the expectations and experiences of students who underwentpersonal genotyping, how they interpreted and applied their results; how thetesting affected the quality of their learning during the course, and what weretheir perceived needs for support.

Results
Students stated that personal genotyping enhanced their engagement with the coursecontent. Although students expressed skepticism over the clinical utility of sometest results, they expressed significant enthusiasm immediately after receivingtheir personal genetic analysis, and were particularly interested in results suchas drug response and carrier testing. However, few reported making behavioralchanges or following up on specific results through a healthcare provider.Students did not report utilizing genetic counseling, despite feeling stronglythat the 'general public' would need these services. In follow-up interviews,students exhibited poor recall on details of the consent and biobankingagreements, but expressed little regret over their decision to undergo genotyping.Students reported mining their raw genetic data, and conveyed a need for furtherconsultation support in their exploration of genetic variants.

Conclusions
Personal genotyping may improve students' self-reported motivation and engagementwith course material. However, consultative support that is different fromtraditional genetic counseling will be necessary to support students. Beforeincorporating personal genotyping into coursework, institutions should leadmulti-disciplinary discussion to anticipate issues and incorporate teachingmechanisms that engage the ethical, legal, and social implications of personalgenotyping, including addressing those found in this study, to go beyond what isoffered by commercial providers.
Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancer
Authors: Guan Zhongzhen , Xu Binghe , DeSilvio Michelle L. , Shen Zhenzhou , Arpornwirat Wichit , Tong Zhongsheng , Lorvidhaya Vicharn , Jiang Zefei , Yang Junlan , Makhson Anatoly , Leung Wai Lim , Russo Mark W. , Newstat Beth , Wang Li , Chen George , Oliva Cristina , Gomez Henry 
Published: March 2013

Purpose Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). Patients and Methods This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety. Results The addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. Conclusion This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.
NMR and DFT Study on Onium Ions Derived from Substituted Fluoranthenes and Benzo[k]fluoranthenes
Authors: Okazaki Takao , Adachi Taisuke , Kitagawa Toshikazu 
Published: March 2013

Abstract
Fluoranthene and benzo[k]fluoranthene (3) are nonalternant polyaromatic hydrocarbons. Their derivatives, 3-acetyl, 8-acetyl, 3-nitro, and 3-aminofluoranthenes (4, 5, 7, and 8) were reacted in FSO3H/SO2ClF and the solutions were observed by NMR measurements at low temperatures, which showed the formation of PAH-substituted onium ions. The most deshielded 13C peaks in fluoranthene frames were observed at 155.7 and 148.7 ppm for 4H+, 154.4 ppm for 5H+, 159.1 and 139.6 ppm for 7H+, and 139.7 ppm for 8H+. Distribution of the positive charges were estimated on the basis of changes in 13C NMR chemical shifts between onium ions and their corresponding parent compounds. Only limited delocalization of positive charges into the aromatic rings was found to occur. GIAO-derived NMR chemical shifts calculated by the DFT method were generally consistent with the experimental chemical shifts. DFT calculations suggested that benzo[k]fluoranthene (3) is favored to be protonated at C-3/C-7 positions. GIAO-derived NICS(1)zz were computed to elucidate aromaticity/antiaromaticity, and the results suggested that the five-membered rings are antiaromatic for cations 4H+, 7H+, 8H+, and 3aH+ (3-benzo[k]fluoranthenium ion).
Mixed Bundling in Two-Sided Markets in the Presence of Installed Base Effects
Authors: Chao Yong , Derdenger Timothy 
Published: March 2013

We analyze mixed bundling in two-sided markets where installed base effects are present and find that the pricing structure deviates from traditional bundling as well as the standard two-sided markets literature—we determine prices on both sides fall with bundling. Mixed bundling acts as a price discrimination tool segmenting the market more efficiently. Consequently, as a by-product of this price discrimination, the two sides are better coordinated, and social welfare is enhanced. We show unambiguously that platform participations increase on both sides of the market. After theoretically evaluating the impact mixed bundling has on prices and welfare, we take the model predictions to data from the portable video game console market. We find empirical support for all theoretical predictions. This paper was accepted by J. Miguel Villas-Boas, marketing.
Organization and Bargaining: Sales Process Choice at Auto Dealerships
Authors: Bennett Victor Manuel 
Published: March 2013

This paper examines how firms' organizational form affects prices negotiated. Negotiated prices are one factor determining whether a vendor or customer captures the value from a transaction. Firms that systematically negotiate more effectively capture more value. Research has investigated individual- and market-level determinants of negotiation outcomes, but little has been done on the firm-level determinants of negotiated prices. I present a first look at one feature, sales process: whether salespeople handle the entire sale in parallel or customers begin with less experienced salespeople who can escalate difficult assignments. I model firms' choice of sales process as a biform game and test predictions of the model using a combination of transaction-level data on new car purchases in the United States and a unique survey of dealership management practices. I find that a serial process has implications consistent with improving firms' bargaining power and reducing customers' outside options. This paper was accepted by Bruno Cassiman, business strategy.
Coinsurance Within Business Groups: Evidence from Related Party Transactions in an Emerging Market
Authors: Jia Nan , Shi Jing , Wang Yongxiang 
Published: March 2013

Using novel transaction-level data on Chinese business groups, this study provides the first direct evidence of the coinsurance theory of business groups by investigating when different types of internal resources are transferred within a business group. We find that in Chinese business groups, a credit crunch experienced by the controlling shareholding firm (the “controller”) of a publicly listed firm increases the loan-based related party transactions (RPTs) including loan guarantees and intercorporate loans provided by the listed firm to the controller. In turn, when the listed firm's performance dips, the controller and its son firms provide more support to the listed firm in the form of non-loan-based RPTs. These findings directly show the dynamic interactions of members within business groups. This paper was accepted by Bruno Cassiman, business strategy.
Cost-Effective and Scalable DNA Extraction Method from Dried Blood Spots
Authors: Saavedra-Matiz Carlos A , Isabelle Jason T , Biski Chad K , Duva Salvatore J , Sweeney Melissa L , Parker April L , Young Allison J , DiAntonio Lisa L , Krein Lea M , Nichols Matthew J , Caggana Michele 
Published: March 2013

BACKGROUNDDried blood spot (DBS) samples have been widely used in newborn screening (NBS) for the early identification of disease to facilitate the presymptomatic treatment of congenital diseases in newborns. As molecular genetics knowledge and technology progresses, there is an increased demand on NBS programs for molecular testing and a need to establish reliable, low-cost methods to perform those analyses. Here we report a flexible, cost-efficient, high-throughput DNA extraction method from DBS adaptable to small- and large-scale screening settings.METHODSGenomic DNA (g.DNA) was extracted from single 3-mm diameter DBS by the sequential use of red cell lysis, detergent-alkaline, and acid-neutralizing buffers routinely used in whole blood and plant tissue DNA extractions. We performed PCR amplification of several genomic regions using standard PCR conditions and detection methods (agarose gel, melting-curve analysis, TaqMan-based assays). Amplicons were confirmed by BigDye® Terminator cycle sequencing and compared with reference sequences.RESULTSHigh-quality g.DNA was extracted from hundreds of DBS, as proven by mutation detection of several human genes on multiple platforms. Manual and automated extraction protocols were validated. Quantification of g.DNA by Oligreen® fluorescent nucleic acid stain demonstrated a normal population distribution closely corresponding with white blood cell counts detected in newborn populations.CONCLUSIONSHigh-quality, amplifiable g.DNA is extractable from DBSs. Our method is adaptable, reliable, and scalable to low- and high-throughput NBS at low cost ($0.10/sample). This method is routinely used for molecular testing in the New York State NBS program.
Alternative genetic code for amino acids and transfer RNA revisited
Authors: Hamashima Kiyofumi , Kanai Akio 
Published: March 2013

AbstractThe genetic code is highly conserved among all organisms and its evolution is thought to be strictly limited. However, an increasing number of studies have reported non-standard codes in prokaryotic and eukaryotic genomes. Most of these deviations from the standard code are attributable to tRNA changes relating to, for example, codon/anticodon base pairing and tRNA/aminoacyl-tRNA synthetase recognition. In this review, we focus on tRNA, a key molecule in the translation of the genetic code, and summarize the most recently published information on the evolutionary divergence of the tRNAs. Surprisingly, although higher eukaryotes, such as the nematode (worm), utilize the standard genetic code, newly identified nematode-specific tRNAs (nev-tRNAs) translate nucleotides in a manner that transgresses the code. Furthermore, a variety of additional functions of tRNAs, beyond their translation of the genetic code, have emerged rapidly. We also review these intriguing new aspects of tRNA, which have potential impacts on translational control, RNA silencing, antibiotic resistance, RNA biosynthesis, and transcriptional regulation.
Serum procalcitonin predicts development of acute kidney injury in patients with suspected infection
Authors: Nie Xin , Wu Bin , He Yong , Huang Xunbei , Dai Zhongqiu , Miao Qiang , Song Haolan , Luo Tongxing , Gao Baoxiu , Wang Lanlan , Li Guixing 
Published: March 2013

AbstractBackground:Procalcitonin (PCT) is an early, sensitive, and accurate marker for diagnosing infection and sepsis. As sepsis and septic shock are dominant causes of acute kidney injury (AKI), we investigated whether PCT is an early predictor of AKI in patients with symptoms of infection.Methods:Between January 2011 and October 2011, 1361 inpatients in West China Hospital who displayed infection symptoms were enrolled in our study. Levels of PCT, serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC) were determined and participants’ renal function was monitored for 3 consecutive days.Results:The rate of AKI occurrence 3 days after enrollment was 14.6%. Higher PCT levels were correlated with higher AKI occurrence rates and higher levels of serum urea, creatinine, and cystatin C (p<0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for PCT was 0.823, making it more predictive (p<0.0001) than SAA, CRP, IL-6, or WBC. The cut-off value of 1.575 ng/mL for PCT had the highest validity for predicting AKI in patients with infection symptoms. The sensitivity, specificity, negative-predictive value (NPV), positive-predictive value (PPV), negative-likelihood ratio (LR-), and positive-likelihood ratio (LR+) for this cut-off value were 61.7%, 84.6%, 93.6%, 37.5%, 0.415, and 4.98, respectively.Conclusions:PCT can be used as a predictive marker for sepsis-induced acute kidney injury in patients with symptoms of infection.