bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palatal Flap Modifications Allow Pedicled Reconstruction of the Skull Base
Authors: Oliver Christopher L. , Hackman Trevor G. , Carrau Ricardo L. , Snyderman Carl H. , Kassam Amin B. , Prevedello Daniel M. , Gardner Paul 
Published: November 2008

AbstractObjectives: Defects after endoscopic expanded endonasal approaches (EEA) to the skull base, have exposed limitations of traditional reconstructive techniques. The ability to adequately reconstruct these defects has lagged behind the ability to approach/resect lesions at the skull base. The posteriorly pedicled nasoseptal flap is our primary reconstructive option; however, prior surgery or tumors can preclude its use. We focused on the branches of the internal maxillary artery, to develop novel pedicled flaps, to facilitate the reconstruction of defects encountered after skull base expanded endonasal approaches.Study Design: Feasibility.Methods: We reviewed radiology images with attention to the pterygopalatine fossa and the descending palatine vessels (DPV), which supply the palate. Using cadaver dissections, we investigated the feasibility of transposing the standard mucoperiosteal palatal flap into the nasal cavity and mobilizing the DPV for pedicled skull base reconstruction.Results: We transposed the palate mucoperiosteum into the nasal cavity through limited enlargement of a single greater palatine foramen. Our method preserves the integrity of the nasal floor mucosa, and mobilizes the DPV from the greater palatine foramen to their origin in the pterygopalatine fossa. Radiological measurements and cadevaric dissections suggest that the transposed, pedicled palatal flap (the Oliver pedicled palatal flap) could be used to reconstruct defects of the planum, sella, and clivus.Conclusions: Our novel modifications to the island palatal flap yield a large (12–18 cm2) mucoperiosteal flap based on a ∼ 3 cm pedicle. The Oliver pedicled palatal flap shows potential for nasal cavity and skull base reconstruction (see video, available online only).
Papillary Thyroid Cancer: Controversies in the Management of Neck Metastasis
Authors: Davidson H Carter , Park Brian J. , Johnson Jonas T. 
Published: November 2008

AbstractObjective/Hypothesis: To describe our institution's experience with the management of cervical metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates.Materials and Methods: Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence.Study Design: Retrospective chart review.Results: The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with “lymph node plucking” procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred.Conclusions: Our data show that limited neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional neck dissection would seem to offer the patient the best opportunity for control of cervical metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral neck and fine needle aspiration of suspicious nodes to avoid undertreating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognosticsignificance of cervical disease persistence and recurrence is still unknown. Patients with cervical metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be overtreated, whereas some remain at risk of death because of disease.
The GNAS1 T393C Polymorphism Predicts Survival in Patients With Advanced Squamous Cell Carcinoma of the Larynx
Authors: Lehnerdt Goetz F. , Franz Peter , Winterhoff Sebastian , Bankfalvi Agnes , Grehl Sara , Lang Stephan , Schmid Kurt W. , Siffert Winfried , Jahnke Klaus , Frey Ulrich H. 
Published: November 2008

AbstractObjectives/Hypothesis: In previous studies, we have demonstrated that the T‐allele of a specific single nucleotide polymorphism (SNP) in the Gαs gene (T393C) correlates with increased Gαs expression and hence apoptosis. The T‐allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro‐ and hypopharynx.Study Design: The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens.Methods: DNA analysis was performed using DNA from paraffin‐embedded tissue samples from 157 patients (142 men, 15 women) with a median follow‐up of 68 (3–143) months. The various genotypes were correlated with the overall survival.Results: Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III–IV) with an apparent gene‐dose effect (P = .0437). Five‐year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01–6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals.Conclusions: The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.
The Therapeutic Effect of OK‐432 (Picibanil) Sclerotherapy for Benign Neck Cysts
Authors: Kim Myung Gu , Kim Sun Gon , Lee Jun Ho , Eun Young Gyu , Yeo Seung Geun 
Published: November 2008

AbstractBackground and Objectives: In general, benign neck cysts are treated by surgical excision. This can present technical difficulties and frequent recurrences, because of insufficient surgery. Sclerosing agents such as OK‐432 have been tested for the nonsurgical treatment of these cysts. We have assessed the efficacy of OK‐432 sclerotherapy for benign neck cysts.Materials and Methods: The study group consisted of 75 patients (42 men, 33 women) diagnosed with and treated for benign neck cysts between March 2001 and December 2007 by intralesional injection of OK‐432. The liquid content of each cyst was aspirated as much as possible, and the same volume of OK‐432 solution was injected. Patients were assessed by ultrasonography or computerized tomography, and therapeutic outcomes and adverse effects were evaluated by patient age, sex, cyst type, and number of injections.Results: Of the 75 treated patients, 31 (41.3%) showed total shrinkage, seven (9.3%) showed near‐total shrinkage (>90% of cyst volume), five (6.6%) showed marked shrinkage (>70% of cyst volume), and 17 (22.7%) showed partial shrinkage (<70% of cyst volume). No response was seen in 15 patients (20%). Despite repeated sclerotherapy, eight patients (10.7%) showed recurrences. Minor adverse effects of therapy included fever, localized pain, and odynophagia but these complications spontaneously disappeared within several days.Conclusions: OK‐432 sclerotherapy is a safe and effective primary alternative to surgery in patients with benign neck cysts.
A Genomic Scan for Selection Reveals Candidates for Genes Involved in the Evolution of Cultivated Sunflower (Helianthus annuus)
Authors: Chapman Mark A. , Pashley Catherine H. , Wenzler Jessica , Hvala John , Tang Shunxue , Knapp Steven J. , Burke John M. 
Published: November 2008

AbstractGenomic scans for selection are a useful tool for identifying genes underlying phenotypic transitions. In this article, we describe the results of a genome scan designed to identify candidates for genes targeted by selection during the evolution of cultivated sunflower. This work involved screening 492 loci derived from ESTs on a large panel of wild, primitive (i.e., landrace), and improved sunflower (Helianthus annuus) lines. This sampling strategy allowed us to identify candidates for selectively important genes and investigate the likely timing of selection. Thirty-six genes showed evidence of selection during either domestication or improvement based on multiple criteria, and a sequence-based test of selection on a subset of these loci confirmed this result. In view of what is known about the structure of linkage disequilibrium across the sunflower genome, these genes are themselves likely to have been targeted by selection, rather than being merely linked to the actual targets. While the selection candidates showed a broad range of putative functions, they were enriched for genes involved in amino acid synthesis and protein catabolism. Given that a similar pattern has been detected in maize (Zea mays), this finding suggests that selection on amino acid composition may be a general feature of the evolution of crop plants. In terms of genomic locations, the selection candidates were significantly clustered near quantitative trait loci (QTL) that contribute to phenotypic differences between wild and cultivated sunflower, and specific instances of QTL colocalization provide some clues as to the roles that these genes may have played during sunflower evolution.
Arabidopsis bZIP60 Is a Proteolysis-Activated Transcription Factor Involved in the Endoplasmic Reticulum Stress Response
Authors: Iwata Yuji , Fedoroff Nina V. , Koizumi Nozomu 
Published: November 2008

Abstract
Proteins synthesized in the endoplasmic reticulum (ER) of eukaryotic cells must be folded correctly before translocation out of the ER. Disruption of protein folding results in the induction of genes for ER-resident chaperones, for example, BiP. This phenomenon is known as the ER stress response. We report here that bZIP60, an Arabidopsis thaliana basic leucine zipper (bZIP) transcription factor with a transmembrane domain, is involved in the ER stress response. When compared with wild-type Arabidopsis plants, homozygous bzip60 mutant plants show a markedly weaker induction of many ER stress-responsive genes. The bZIP60 protein resides in the ER membrane under unstressed condition and is cleaved in response to ER stress caused by either tunicamycin or DTT. The N-terminal fragment containing the bZIP domain is then translocated into the nucleus. Cleavage of bZIP60 is independent of the function of Arabidopsis homologs of mammalian S1P and S2P proteases, which mediate the proteolytic cleavage of the mammalian transcription factor ATF6. In Arabidopsis, expression of the bZIP60 gene and cleavage of the bZIP60 protein are observed in anthers in the absence of stress treatment, suggesting that the ER stress response functions in the normal development of active secretory cells.
Genome characterization ofPyrenophora tritici‐repentisisolates reveals high plasticity and independent chromosomal location ofToxAandToxB
Authors: ABOUKHADDOUR R. , CLOUTIER S. , BALLANCE G. M. , LAMARI L. 
Published: November 2008

SUMMARYThe fungusPyrenophora tritici‐repentis(Died.) causes tan spot, an important leaf disease of wheat worldwide. Isolates of this pathogen have been collected and characterized into eight races on the basis of their ability to produce three different host‐selective toxins. The karyotype of 47 isolates was determined by pulsed field gel electrophoresis. The collection originated from different parts of the world and included genotypes from all races. A single isolate was characterized for each of races 3, 4 and 6, whereas fourteen, five, nine, five and eleven isolates were karyotyped for races 1, 2, 5, 7 and 8, respectively. The survey showed that the chromosome number ofP. tritici‐repentiswas highly variable, with some isolates having as few as eight chromosomes, but others having 11 or more. Similarly, the genome size ranged from 25.5 to 48.0 Mb, and individual chromosome sizes ranged from 1.3 to more than 5.7 Mb. Considerable variation was observed in karyotype patterns among theP. tritici‐repentisisolates tested. A total of 29 different karyotypes was identified among the 47 isolates. These chromosome level variations were as variable for isolates within a race as for isolates across races. Southern blot analysis of the 47 isolates withToxAandToxBprobes revealed that the toxin genes were always located on different chromosomes. Furthermore, with six chromosome‐specific single‐copy probes, theToxA‐carrying chromosome was shown to be homologous among the Ptr ToxA‐producing isolates, with a related chromosome in the non‐ToxA‐producing isolates, suggesting that the chromosome on whichToxAgenerally resides is of an essential nature. Interestingly, a molecular rearrangement involving a translocation ofToxAto a different chromosome was identified in one isolate.
Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels
Authors: WONG V. W.‐S. , WONG G. L.‐H. , TSANG S. W.‐C. , HUI A. Y. , CHAN A .W.‐H. , CHOI P. C.‐L. , CHIM A. M.‐L. , CHU S. , CHAN F. K.‐L. , SUNG J. J.‐Y. , CHAN H. L.‐Y. 
Published: November 2008

SummaryBackground  Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear.Aim  To evaluate the metabolic and histological features of NAFLD patients with different ALT levels.Methods  A total of 173 consecutive patients with biopsy‐proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared.Results  Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within‐patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis.Discussion  Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non‐alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level.
High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program
Authors: Mikhael Joseph R. , Belch Andrew R. , Prince H. Miles , Lucio Maria Nambo , Maiolino Angelo , Corso Alessandro , Petrucci Maria Teresa , Musto Pellegrino , Komarnicki Mieczyslaw , Stewart A. Keith 
Published: November 2008

SummaryPhase 2 trials have demonstrated that bortezomib ± dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open‐label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3‐week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after ≥2 cycles or for stable disease after ≥4 cycles. Responses were assessed based on M‐protein changes. Overall response rate was 67%, including 11% complete (100% M‐protein reduction), 22% very good partial (75–99% reduction), 18% partial (50–74% reduction), and 16% minimal response (25–49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.
Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis: a report of seven cases from a regional UK TTP registry
Authors: McDonald V. , Laffan M. , Benjamin S. , Bevan D. , Machin S. , Scully M. A. 
Published: November 2008

SummaryThrombotic thrombocytopenic purpura (TTP) may be idiopathic or secondary. We report seven TTP cases precipitated by pancreatitis. The patients were admitted with acute pancreatitis and at that time had no clinical or laboratory features of TTP. The median time to develop TTP after pancreatitis was 3 d. The patients had moderately reduced ADAMTS13 activity (mean activity 49%; normal range 66–126%) with no evidence of anti‐ADAMTS13 inhibitory autoantibodies. The median number of plasma exchanges to remission was 10 (range 7–14) and no additional treatment with immunosuppression was required to maintain remission. There have been no relapses to date.
Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study
Authors: Bomben Riccardo , Dal Bo Michele , Capello Daniela , Forconi Francesco , Maffei Rossana , Laurenti Luca , Rossi Davide , Del Principe Maria Ilaria , Zucchetto Antonella , Bertoni Francesco , Rossi Francesca Maria , Bulian Pietro , Cattarossi Ilaria , Ilariucci Fiorella , Sozzi Elisa , Spina Valeria , Zucca Emanuele , Degan Massimo , Lauria Francesco , Del Poeta Giovanni , Efremov Dimitar G. , Marasca Roberto , Gaidano Gianluca , Gattei Valter 
Published: November 2008

SummaryA fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B‐cell receptors (BCR), i.e. characterized by non‐random combinations of immunoglobulin heavy‐chain variable (IGHV) genes and heavy‐chain complementarity determining region‐3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such ‘stereotyped’ BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time‐to‐treatment (TTT) and presence of known prognosticators. Sixty‐nine clusters (319 IG‐rearrangements, 22·4%) with stereotyped BCR were identified. Among 30 confirmed clusters (≥3 IG‐rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster‐biased amino acid changes were found throughout IGHV sequences of these ‘M clusters’. Regarding clinical outcome: (i) UM CLL from the IGHV1‐2/1‐3/1‐18/1‐46/7‐4‐1/IGKV1‐39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3‐21/IGLV3‐21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3‐21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.
Ca2+‐CaM activation of AMP deaminase contributes to adenine nucleotide dysregulation and phosphatidylserine externalization in human sickle erythrocytes
Authors: Sabina Richard L. , Wandersee Nancy J. , Hillery Cheryl A. 
Published: November 2008

SummaryCa2+‐calmodulin (Ca2+‐CaM) activates erythrocyte adenosine monophosphate deaminase (AMPD) in conditions of disturbed calcium homeostasis, prompting us to investigate adenine nucleotide metabolic dysregulation in sickle cell disease (SCD). However, higher ATP concentrations in reticulocytes, compared to erythrocytes, confound a comparative evaluation of SCD and normal RBCs. Therefore, a combination of centrifugation and antiCD71‐labelled magnetic bead selection was used to prepare reticulocyte‐poor fractions (reticulocytes <4% of total RBCs) of SCD RBCs. ATP and total adenine nucleotide concentrations were 12% lower in sickle erythrocytes compared to normal erythrocytes and inosine monophosphate (IMP) concentrations were threefold elevated (allP < 0·05). Furthermore, preincubation with a diffusible CaM antagonist slowed IMP accumulation in sickle erythrocytes during an experimental period of energy imbalance, thus showing that Ca2+‐CaM activates AMPD in SCD. Finally, adenine treatment (100 μmol/l) ofex vivoSCD RBCs significantly expanded ATP levels (16% higher) and reduced phosphatidylserine (PS)‐exposure, specifically those cells with the highest levels of PS externalization (46% fewer events) (bothP‐values <0·05 compared to untreated samples). We conclude that Ca2+‐CaM activation of AMPD contributes to increased turnover of the adenine nucleotide pool in sickle erythrocytes and that this metabolic dysregulation promotes PS exposure that may contribute to the pathogenesis of SCD.
In vitro anti‐leukaemia activity of sphingosine kinase inhibitor
Authors: Ricci Clara , Onida Francesco , Servida Federica , Radaelli Franca , Saporiti Giorgia , Todoerti Katia , Deliliers Giorgio Lambertenghi , Ghidoni Riccardo 
Published: November 2008

SummaryCompelling evidence indicates the role of sphingosine kinase 1 (SPHK1) deregulation in the processes of carcinogenesis and acquisition of drug resistance, providing the rationale for an effective anti‐cancer therapy. However, no highly selective inhibitors of SPHK1 are available for in vitro and in vivo studies, except for the newly discovered ‘SK inhibitor’ (SKI). The present study showed that, in a panel of myeloid leukaemia cell lines, basal level of SPHK1 correlated with the degree of kinase inhibition by SKI. Exposure to SKI caused variable anti‐proliferative, cytotoxic effects in all cell lines. In particular, SKI induced an early, significant inhibition of SPHK1 activity, impaired cell cycle progression and triggered apoptosis in K562 cells. Moreover, SKI acted synergistically with imatinib mesylate (IM) to inhibit cell growth and survival. Finally, the inhibitor affected the clonogenic potential and viability of primary cells from chronic myeloid leukaemia (CML) patients, including one harbouring the IM‐insensitive Abl kinase domain mutation T315I. Due to the fact that the phenomenon of resistance to IM remains a major issue in the treatment of patients with CML, the identification of alternative targets and new drugs may be of clinical relevance.