bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging of intramedullary spinal cord lesions: A pictorial review
Authors: Watts Jane , Box Georgia Alexandra , Galvin Angela , Van Tonder Frans , Trost Nicholas , Sutherland Thomas 
Published: July 2014

SummaryMagnetic resonance imaging (MRI) is the modality of choice for the investigation of intramedullary lesions of the spinal cord. A wide variety of conditions may result in similar imaging findings on MRI, and it is essential that the reporting radiologist have a detailed understanding of spinal cord anatomy, the pertinent imaging features of specific intramedullary lesions and the typical clinical presentation of those conditions to aid clinicians to make a prompt diagnosis. This pictorial essay discusses the clinical features and MRI appearance of a number of intramedullary conditions, which can be broadly categorised as congenital, demyelinating, vascular, neoplastic or infectious, and highlights their differentiating features.
Imprinted loci in domestic livestock species as epigenomic targets for artificial selection of complex traits
Authors: Magee D. A. , Spillane C. , Berkowicz E. W. , Sikora K. M. , MacHugh D. E. 
Published: July 2014

SummaryThe phenomenon of genomic imprinting, whereby a subset of mammalian genes display parent‐of‐origin‐specific monoallelic expression, is one of the most active areas of epigenetics research. Over the past two decades, more than 100 imprinted mammalian genes have been identified, while considerable advances have been made in elucidating the molecular mechanisms governing imprinting. These studies have helped to unravel the epigenome – a separate layer of regulatory information contained in eukaryotic chromosomes that influences gene expression and phenotypes without involving changes to the underlying DNA sequence. Although most studies of genomic imprinting in mammals have focussed on mouse models or human biomedical disorders, there is burgeoning interest in the phenotypic effects of imprinted genes in domestic livestock species. In particular, research has focused on imprinted genes influencing foetal growth and development, which are associated with economically important production traits in cattle, sheep and pigs. These findings, when coupled with the data emerging from the various different livestock genome projects, have major implications for the future of animal breeding, health and management. Here, we review current scientific knowledge regarding genomic imprinting in livestock species and evaluate how this information can be used in modern livestock improvement programmes.
Goat casein genotypes are associated with milk production traits in the Sarda breed
Authors: Vacca G. M. , Dettori M. L. , Piras G. , Manca F. , Paschino P. , Pazzola M. 
Published: July 2014

SummaryThe aim of the current work was to analyze, in the Sarda breed goat, genetic polymorphism within the casein genes and to assess their influence on milk traits. Genetic variants at the CSN1S1, CSN2, CSN1S2 and CSN3 gene loci were investigated using PCR‐based methods, cloning and sequencing. Strong alleles prevailed at the CSN1S1 gene locus and defective alleles also were revealed. Null alleles were evidenced at each calcium‐sensitive gene locus. At the CSN3 gene locus, we observed a prevalence of the CSN3 A and B alleles; the occurrence of rare alleles such as CSN3 B'', C, C', D, E and M; and the CSN3 S allele (GenBank KF644565) described here for the first time in Capra hircus. Statistical analysis showed that all genes, except CSN3, significantly influenced milk traits. The CSN1S1 BB and AB genotypes were associated with the highest percentages of protein (4.41 and 4.40 respectively) and fat (5.26 and 5.34 respectively) (P < 0.001). A relevant finding was that CSN2 and CSN1S2 genotypes affected milk protein content and yield. The polymorphism of the CSN2 gene affected milk protein percentage with the highest values recorded in the CSN2 AA goats (4.35, at P < 0.001). The CSN1S2 AC goats provided the highest fat (51.02 g/day) and protein (41.42 g/day) (P < 0.01) production. This information can be incorporated into selection schemes for the Sarda breed goat.
Dose‐Intensified Granulocyte‐Monocyte Apheresis in Therapy Refractory Ulcerative Colitis
Authors: Schultheiß Caroline , Weischenberg René , Herrmann Andrea , Haller Bernhard , Schmid Roland M. , Reindl Wolfgang , Huber Wolfgang 
Published: July 2014

AbstractGranulocyte‐monocyte apheresis (GMA) is an emerging therapeutic option in active course of ulcerative colitis (UC). Appropriate GMA dose, including total number, frequency, and duration of the individual GMA session, is a matter of debate. It was the aim of the present study to evaluate the efficacy of a dose‐intensified GMA regimen in patients with moderately to severely active UC. A prospective open‐label, single‐center study was performed in 10 patients with active UC (Rachmilewitz Clinical Activity Index [CAI] ≥ 8 points; Rachmilewitz Endoscopic Index ≥ 7 points). Patients had failed to improve after treatment with steroids and/or immunomodulators. GMA was performed twice weekly for 2 h to a maximum of 10 sessions. In each GMA session, the adsorber was changed after 1 h of treatment time. Four patients achieved remission with a CAI ≤ 4 points. Three patients had a response with an improvement of CAI of ≥3 points. Three patients showed no benefit from GMA. The quality of life score determined by the inflammatory bowel disease questionnaire‐Deutschland increased by 26 points in median. First and second filters had similar efficiency in granulocyte and monocyte adsorption. No major adverse effects were observed. Dose‐intensified GMA as reported in this study provided an encouraging short‐term response rate of 70% in patients with moderately to severely active UC not responding to standard steroid or immunomodulator therapy. Although all patients relapsed not later than 16 weeks, GMA might be useful to reduce steroid and immunomodulator usage, or to delay surgery in this patient group.
Children's trust in unexpected oral versus printed suggestions: Limitations of the power of print
Authors: Eyden Julie , Robinson Elizabeth J. , Einav Shiri 
Published: July 2014

Children have a bias to trust spoken testimony, yet early readers have an even stronger bias to trust print. Here, we ask how enduring is the influence of printed testimony: Can the learning be applied to new scenarios? Using hybrid pictures more dominant in one animal species (e.g., squirrel) than another (e.g., rabbit), we examined 3–6‐year‐olds' (N = 130) acceptance of an unexpected, non‐dominant label suggested only orally or via print. Consistent with previous findings, early readers, but not pre‐readers, accepted printed labels more frequently than when spoken. Children were then presented with identical but unlabelled hybrid exemplars and frequently applied the non‐dominant labels to these. Despite early readers' prior greater acceptance of text, when oral suggestions were accepted they retained a greater influence. Findings highlight potential implications for educators regarding knowledge being applied to new scenarios: For early readers, unexpected information from text may be fragile, while a greater confidence might be placed in such information gained from spoken testimony.
Safety and clinical outcomes of patients treated with abiraterone acetate after docetaxel: results of the Italian Named Patient Programme
Authors: Caffo Orazio , De Giorgi Ugo , Fratino Lucia , Lo Re Giovanni , Basso Umberto , D'Angelo Alessandro , Donini Maddalena , Verderame Francesco , Ratta Raffaele , Procopio Giuseppe , Campadelli Enrico , Massari Francesco , Gasparro Donatello , Macrini Sveva , Messina Caterina , Giordano Monica , Alesini Daniele , Zustovich Fable , Fraccon Anna P. , Vicario Giovanni , Conteduca Vincenza , Maines Francesca , Galligioni Enzo 
Published: July 2014

ObjectiveTo assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP).Patients and MethodsWe retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals.ResultsWe assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3–4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression‐free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases.ConclusionsOur data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post‐docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.
Medium‐term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer
Authors: Thompson James E. , Hayen Andrew , Landau Adam , Haynes Anne‐Maree , Kalapara Arveen , Ischia Joseph , Matthews Jayne , Frydenberg Mark , Stricker Phillip D. 
Published: July 2014

ObjectiveTo assess, in men undergoing active surveillance (AS) for low‐risk prostate cancer, whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy.Patients and MethodsRetrospective analysis of prospectively collected data from two cohorts with localised prostate cancer (1998–2012) undergoing AS. Prostate cancer‐specific, metastasis‐free and treatment‐free survival, unfavourable disease and significant cancer at radical prostatectomy (RP) were compared for standard (<12 core, median 10) vs saturation (>12 core, median 16), and transrectal vs transperineal biopsy, using multivariate analysis.ResultsIn all, 650 men were included in the analysis with a median (mean) follow‐up of 55 (67) months. Prostate cancer‐specific, metastasis‐free and biochemical recurrence‐free survival were 100%, 100% and 99% respectively. Radical treatment‐free survival at 5 and 10 years were 57% and 45% respectively (median time to treatment 7.5 years). On Kaplan–Meier analysis, saturation biopsy was associated with increased objective biopsy progression requiring treatment (log‐rank P = 0.01). On multivariate Cox proportional hazards analysis, saturation biopsy (hazard ratio 1.68, P < 0.01) but not transperineal approach (P = 0.89) was associated with increased objective biopsy progression requiring treatment. On logistic regression analysis of 179 men who underwent RP for objective progression, transperineal biopsy was associated with lower likelihood of unfavourable RP pathology (odds ratio 0.42, P = 0.03) but saturation biopsy did not alter the likelihood (P = 0.25). Neither transperineal nor saturation biopsy altered the likelihood of significant vs insignificant cancer at RP (P = 0.19 and P = 0.41, respectively).ConclusionsAS achieved satisfactory oncological outcomes. Saturation biopsy increased progression to treatment on AS; longer follow‐up is needed to determine if this represents beneficial earlier detection of significant disease or over‐treatment. Transperineal biopsy reduced the likelihood of unfavourable disease at RP, possibly due to earlier detection of anterior tumours.
Mark4 promotes adipogenesis and triggers apoptosis in 3T3‐L1 adipocytes by activating JNK1 and inhibiting p38MAPK pathways
Authors: Feng Min , Tian Liang , Gan Lu , Liu Zhenjiang , Sun Chao 
Published: July 2014

Background InformationMicrotubule affinity‐regulating kinase 4 (MARK4) deficiency has been reported to negatively regulate diet‐induced obesity and to mitigate insulin resistance in knockout mice, and thus may play a role in metabolic syndrome. However, the details of the molecular mechanism have yet to be revealed and the impacts of MARK4 on apoptosis remain unexplored. This study investigated the role of Mark4 in the regulation of lipid accumulation and apoptosis in adipocytes and analysed signalling pathways involved.ResultsWe found that Mark4 significantly up‐regulated the expression of gene sterol regulatory element binding protein‐1c (SREBP‐1c), fatty acid synthase (FAS), acetyl‐CoA carboxylase‐α (ACCα) and peroxisome proliferator activated receptor‐γ (PPARγ); and reduced the protein contents of adipose triglyceride lipase (ATGL), as evidenced by the dramatic increasing lipid droplet accumulation in 3T3‐L1 cells. Furthermore, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) apoptosis assay showed that Mark4 triggered apoptosis of adipocytes; and apoptosis was confirmed by the decreased protein contents of B‐cell lymphoma‐2 (Bcl‐2), full‐length caspase‐3 and full‐length caspase‐9, as well as the increased expression of Bax, cleaved caspase‐3 and cleaved caspase‐9. Analysis of special inhibitors allowed us to offer the following explanation for these impacts of Mark4: activation of Jun N‐terminal kinase1 (JNK1) promoted both apoptosis and adipogenesis, whereas inhibition of the p38 mitogen‐activated protein kinase (p38MAPK) pathway contributed to lipid accumulation alone.ConclusionsMark4 promotes adipogenesis in 3T3‐L1 adipocytes by activating the JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway. We conclude that anti‐Mark4 therapy targetted to inhibit lipid accumulation and apoptosis of adipocytes shows potential as a novel therapeutic strategy for treatment of obesity‐associated metabolic complications.
Conformational flexibility of the agonist binding jaw of the human P2X3 receptor is a prerequisite for channel opening
Authors: Kowalski M , Hausmann R , Dopychai A , Grohmann M , Franke H , Nieber K , Schmalzing G , Illes P , Riedel T 
Published: July 2014

Background and PurposeIt is assumed that ATP induces closure of the binding jaw of ligand‐gated P2X receptors, which eventually results in the opening of the membrane channel and the flux of cations. Immobilization by cysteine mutagenesis of the binding jaw inhibited ATP‐induced current responses, but did not allow discrimination between disturbances of binding, gating, subunit assembly or trafficking to the plasma membrane.Experimental ApproachA molecular model of the pain‐relevant human (h)P2X3 receptor was used to identify amino acid pairs, which were located at the lips of the binding jaw and did not participate in agonist binding but strongly approached each other even in the absence of ATP.Key ResultsA series of cysteine double mutant hP2X3 receptors, expressed in HEK293 cells or Xenopus laevis oocytes, exhibited depressed current responses to α,β‐methylene ATP (α,β‐meATP) due to the formation of spontaneous inter‐subunit disulfide bonds. Reducing these bonds with dithiothreitol reversed the blockade of the α,β‐meATP transmembrane current. Amino‐reactive fluorescence labelling of the His‐tagged hP2X3 receptor and its mutants expressed in HEK293 or X. laevis oocytes demonstrated the formation of inter‐subunit cross links in cysteine double mutants and, in addition, confirmed their correct trimeric assembly and cell surface expression.Conclusions and ImplicationsIn conclusion, spontaneous tightening of the binding jaw of the hP2X3 receptor by inter‐subunit cross‐linking of cysteine residues substituted at positions not directly involved in agonist binding inhibited agonist‐evoked currents without interfering with binding, subunit assembly or trafficking.
Synthesis and Biological Evaluation of 5‐Nitropyrimidine‐2,4‐dione Analogues as Inhibitors of Nitric Oxide and iNOS Activity
Authors: Ma Liang , He Linhong , Lei Lei , Liang Xiaolin , Lei Kai , Zhang Ronghong , Yang Zhuang , Chen Lijuan 
Published: July 2014

Fifty two compounds based on 5‐nitropyrimidine‐2,4‐dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50: 8.6 μm) on lipopolysaccharide‐induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50: 6.2 μm), as well as exerted no potential cytotoxicity (IC50 > 80.0 μm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan‐induced paw edema of male ICR mice.
Phylogeny of fossil and extant glypheid and litogastrid lobsters (Crustacea, Decapoda) as revealed by morphological characters
Authors: Charbonnier Sylvain , Audo Denis , Barriel Véronique , Garassino Alessandro , Schweigert Günter , Simpson Martin 
Published: July 2014

AbstractA phylogenetic analysis of a total of 31 species: 27 fossil species from seven families (Glypheidae, Litogastridae, Mecochiridae, Pemphicidae, Erymidae, Clytiopsidae, Chimaerastacidae), and four extant species from three families (Glypheidae, Nephropidae, Stenopodidae) is proposed. Most of the genera considered are coded exclusively based upon their type species and, as much as possible, based upon the type specimens. The cladistic analysis demonstrates that the glypheidean lobsters (infraorder Glypheidea) form a monophyletic group including two superfamilies: Glypheoidea and Pemphicoidea new status. Glypheoidea includes three families: Glypheidae, Mecochiridae and Litogastridae. Litogastridae is the sister group of the clade Glypheidae + Mecochiridae. Pemphicoidea includes a single family: Pemphicidae. A new classification of Glypheidea is proposed and currently known genera are rearranged based upon the phylogenetic analysis.
The prognostic impact of the log odds of positive lymph nodes in colon cancer
Authors: Arslan N. C. , Sokmen S. , Canda A. E. , Terzi C. , Sarioglu S. 
Published: July 2014

AbstractAimThis study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer.MethodFour hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed.ResultsThe 5‐year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node‐negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node‐negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor.ConclusionConventional TNM staging for nodes (pN) and LNR status cannot reliably classify node‐negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN.
Does rectal cancer height influence the oncological outcome?
Authors: Bhangu A. , Rasheed S. , Brown G. , Tait D. , Cunningham D. , Tekkis P. 
Published: July 2014

AbstractAimThe influence of the height of rectal cancer from the anal verge on the oncological outcome is controversial. This study aimed to determine the influence of the height of the tumour on the survival of patients treated in a specialized rectal cancer unit.MethodPatients undergoing surgery for primary rectal cancer from 2006 to 2013 were identified from a prospectively maintained rectal cancer database. Those requiring total or multicompartmental pelvic exenteration were excluded. Low cancer was defined as tumour < 5 cm from the anal verge, as assessed by endoscopy and/or digital rectal examination. The primary outcome was 3‐year disease‐free survival (DFS).ResultsOf 340 patients, 203 (59.7%) had low cancer. There were 302 (89%) restorative and 38 (11%) nonrestorative procedures. The rate of positive circumferential resection margin was similar for low compared with high cancer (3.4% vs 2.9%, P = 1.0) and for restorative compared with nonrestorative procedures in low cancer only (3.0% and 5.3%, P = 0.619). Low compared with high anterior resection was associated with increased anastomotic leakage (8.5% vs 2.2%, P = 0.023). Three‐year DFS was similar for low and high resection (82% vs 86%, P = 0.305) and between restorative vs nonrestorative procedures in low cancer only (88% vs 77%, P = 0.215). In an adjusted model, low height did not lead to worse survival outcome (3‐year DFS hazard ratio 0.54, 95% CI 0.24–1.24, P = 0.147).ConclusionWith careful planning and a multidisciplinary approach, equivalent oncological outcome can be achieved for patients with rectal cancer who undergo curative surgery regardless of differences in tumour characteristics, location and operation performed.
Reversion of developmental mode in insects: evolution from long germband to short germband in the polyembrionic wasp Macrocentrus cingulum Brischke
Authors: Sucena Élio , Vanderberghe Koen , Zhurov Vladimir , Grbić Miodrag 
Published: July 2014

SUMMARYGermband size in insects has played a central role in our understanding of insect patterning mechanisms and their evolution. The polarity of evolutionary change in insect patterning has been viewed so far as the unidirectional shift from the ancestral short germband patterning of basal hemimetabolous insects to the long germband patterning observed in most modern Holometabola. However, some orders of holometabolic insects display both short and long germband development, though the absence of a clear phylogenetic context does not permit definite conclusions on the polarity of change. Derived hymenoptera, that is, bees and wasps, represent a classical textbook example of long germband development. Yet, in some wasps putative short germband development has been described correlating with lifestyle changes, namely with evolution of endoparasitism and polyembryony. To address the potential reversion from long to short germband, we focused on the family Braconidae, which displays ancestral long germband development, and examined the derived polyembryonic braconid Macrocentrus cingulum. Using SEM analysis of M. cingulum embryogenesis coupled with analyses of embryonic patterning markers, we show that this wasp evolved short germband embryogenesis secondarily, in a way that is reminiscent of embryogenesis in the beetle Tribolium castaneum. This work shows that the evolution of germband size in insects is a reversible process that may correlate with other life‐history traits and suggests broader implications on the mechanisms and evolvability of insect development.