bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late‐evening snack with branched‐chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma
Authors: Morihara Daisuke , Iwata Kaoru , Hanano Takayuki , Kunimoto Hideo , Kuno Shizuka , Fukunaga Atsushi , Yotsumoto Kaoru , Takata Kazuhide , Tanaka Takashi , Sakurai Kunitoshi , Iwashita Hideyuki , Ueda Shu‐ichi , Hirano Genryu , Yokoyama Keiji , Nakane Hidetoshi , Nishizawa Shinya , Yoshikane Makoto , Anan Akira , Takeyama Yasuaki , Kakumitsu Shigeru , Kitamura Yuji , Sakamoto Masaharu , Irie Makoto , Shakado Satoshi , Sohda Tetsuro , Watanabe Hiroshi , Sakisaka Shotaro 
Published: January 2012

Aim:  This prospective study was designed to examine whether consumption of a branched‐chain amino acid (BCAA)‐enriched nutrient mixture as a late‐evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC).Methods:  An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M‐BCAA) administration group, or a LES with BCAA (LES‐BCAA) administration group. Liver function testing was performed and Child–Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post‐RFA.Results:  Compared to the control and M‐BCAA groups, the LES‐BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post‐RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES‐BCAA group at 4 and 12 weeks post‐RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement‐induced vomiting.Conclusion:  LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie‐containing BCAA is administrated to LC patients with impaired glucose tolerance.
Does Audit Market Concentration Harm the Quality of Audited Earnings? Evidence from Audit Markets in 42 Countries*
Authors: Francis Jere R. , Michas Paul N. , Seavey Scott E. 
Published: January 2012

AbstractAudit regulators around the world have expressed concern over market dominance by Big 4 accounting firms and the potential adverse effect it may have on the quality of audited financial statements. We use cross‐country variation in the audit market structure of 42 countries to examine two separate aspects of Big 4 dominance: (1) Big 4 market concentration as a group relative to non–Big 4 auditors; and (2) concentration within the Big 4 group in which one or more of the Big 4 firms is dominant relative to the other Big 4 firms. We find that in countries where the Big 4 (as a group) conduct more listed company audits, both Big 4 and non–Big 4 clients have higher quality audited earnings compared to clients in countries with smaller Big 4 market shares. In contrast, in countries where there is a greater concentration within the Big 4 group, we find that Big 4 clients have lower quality audited earnings compared to countries with more evenly distributed market shares among the Big 4. Thus concentration within the Big 4 group appears to be detrimental to audit quality in a country and of legitimate concern to regulators and policymakers. However, Big 4 dominance per se does not appear to harm audit quality and is in fact associated with higher earnings quality, after controlling for other country characteristics that potentially affect earnings quality.
Effect of Acupuncture on Perception Threshold: A Randomised Controlled Trial
Authors: Wu Shuang , Yamaguchi Hidenori , Shibutani Koh 
Published: January 2012

Objective To determine the current perception thresholds (CPTs) for arm and mental foramen areas to enable a quantitative evaluation of the effectiveness of acupuncture treatment. Methods Ninety-eight volunteers enrolled as participants and were randomly assigned to one of three groups: an acupuncture group (34 subjects); a sham acupuncture group (32 subjects) and a waiting group (32 subjects). CPTs for the arm and mental foramen areas were determined before and after acupuncture at LI4 Hegu of the left hand. A Neurometer CPT was used to evaluate the perception threshold at the homolateral mental foramen and arm. For further exploration, thresholds of homolateral and contralateral mental foramina were determined before and after acupuncture in a subgroup of 13 participants in the acupuncture group. Results Acupuncture at LI4 increased the perception thresholds of the left mental foramen in the acupuncture group significantly (p<0.01). The increases were significantly greater than in the control group for all frequencies, and significantly greater than sham acupuncture for 250 Hz and 5 Hz. In the subgroup, only the CPTs at 5 Hz increased significantly for the contralateral mental foramen. Conclusions Acupuncture at LI4 increases the perception threshold in the mandibular area, but not in the arm. This finding is probably related to the analgesic effect of acupuncture.
Eosinophils in the oesophageal mucosa: clinical, pathological and epidemiological relevance in children: a cohort study
Authors: Cohen Marta C , Rao Prithviraj , Thomson Mike , Al-Adnani Mudher 
Published: January 2012

ObjectivesEosinophilic oesophagitis (EO) shows eosinophilic infiltration of the mucosa and can present with symptoms indistinguishable from gastrooesophageal reflux disease (GORD). The authors describe the clinical, endoscopic and histopathological features of all cases of histological EO presenting during 2007–2008 with a 2-year follow-up. The incidence of paediatric EO and the features of a subgroup with features of both GORD and EO (‘overlap’ syndrome (OS)) are described.DesignBiopsies with an average of 15 eosinophils/high-power field (HPF) were reviewed in the cohort. OS was suggested when there was coexistence of clinical and histological features of EO and GORD (abnormal pH study), which improved with proton pump inhibitors.SettingTertiary care.ParticipantsAll cases with ≥15 eosinophils/HPF entered the study.Primary outcome measuresPatients with EO had an average of 15 eosinophils/HPF.Secondary outcome measuresOther histological features of EO included microabscesses, dilated intercellular spaces, basal cell hyperplasia, papillary elongation, etc.Results24 cases of EO were identified, 13 men and 11 women. The incidence of paediatric oesophageal eosinophilia in the region was 9/100 000 children. 11 of the 24 patients (46%) presented with some form of allergy, six with poor feeding/food aversion, five with dysphagia and four with vomiting. After follow-up, 56.5% were confirmed to have EO, 30.5% responded to treatment for GORD and were categorised as OS, 9% developed eosinophilic gastroenteritis and 4% did not have further upper gastrointestinal symptoms.ConclusionsAccurate diagnosis of EO, especially the differentiation from GORD, requires appropriate clinicopathological correlation. A significant proportion of patients with eosinophilia in the mucosa also have GORD (OS). These patients improve after treating the underlying GORD. The study was registered as a Service Evaluation with the Trust (number SE74).
Cancer risk with folic acid supplements: a systematic review and meta-analysis
Authors: Wien Tale Norbye , Pike Eva , Wisløff Torbjørn , Staff Annetine , Smeland Sigbjørn , Klemp Marianne 
Published: January 2012

ObjectiveTo explore if there is an increased cancer risk associated with folic acid supplements given orally.DesignSystematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included.Data sourcesCochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals.ResultsFrom 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38 233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality.ConclusionsA meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk.
Ethnic differences in disease presentation of uterine cancer in New Zealand women
Authors: Firestone Ridvan Tupai , Ellison-Loschmann Lis , Shelling Andrew N , Ekeroma Alec , Ikenasio-Thorpe Bettina A , Pearce Neil , Jeffreys Mona 
Published: January 2012

ObjectivesLittle is known about the ethnic differences in disease presentation of uterine cancer in New Zealand women. The objectives of this study were two-fold: (1) to estimate the incidence and mortality of uterine cancer among women in New Zealand and (2) to examine the association of ethnicity and socioeconomic status with tumour stage and grade, at presentation of uterine cancer.MethodsRetrospective survey of cancer cases identified from the New Zealand Cancer Registry. The authors analysed all 3203 uterine cancer cases registered with the New Zealand Cancer Registry during the period 1 January 1997 to 31 December 2006. Ethnic groups were defined based on the self-identified ethnicity recorded on the cancer registry: Ma–ori, Pacific and non-M–aori non-Pacific women. Socioeconomic status was categorised as quintiles of the New Zealand Deprivation Index 2006. The mortality to incidence ratio was used as a measure of prognosis. Logistic regression was used to estimate age, ethnic and deprivation adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsPacific and M–aori women have higher incidence (32.4 and 17.7 per 100 000 women, respectively) and mortality rates of uterine cancer (12.1 and 7.4 per 100 000 women, respectively). Women in the most deprived areas are more likely to present with an advanced stage of uterine cancer (OR 1.64, 95% CI 1.09–2.48). M–aori and Pacific women are less likely to present with well-differentiated tumours (OR 0.69, 95% CI 0.52–0.92 and OR 0.72, 95% CI 0.52–0.99, respectively).ConclusionsM–aori and Pacific women, and those from lower socioeconomic areas, are more likely to present with advanced uterine cancer.
COUNTING SINGULARITIES VIA FITTING IDEALS
Authors: JORGE-PÉREZ V. H. , MIRANDA A. J. , SAIA M. J. 
Published: January 2012

The stable singularities of differential map germs constitute the main source of studying the geometric and topological behavior of these maps. In particular, one interesting problem is to find formulae which allow us to count the isolated stable singularities which appear in the discriminant of a stable deformation of a finitely determined map germ. Mond and Pellikaan showed how the Fitting ideals are related to such singularities and obtain a formula to count the number of ordinary triple points in map germs from ℂ2to ℂ3, in terms of the Fitting ideals associated with the discriminant.In this article we consider map germs from (ℂn+m, 0) to (ℂm, 0), and obtain results to count the number of isolated singularities by means of the dimension of some associated algebras to the Fitting ideals. First in Corollary 4.5 we provide a way to compute the total sum of these singularities. In Proposition 4.9, for m = 3 we show how to compute the number of ordinary triple points. In Corollary 4.10 and with f of co-rank one, we show a way to compute the number of points formed by the intersection between a germ of a cuspidal edge and a germ of a plane.Furthermore, we show in some examples how to calculate the number of isolated singularities using these results.
LRIG1 Modulates Cancer Cell Sensitivity to Smac Mimetics by Regulating TNFα Expression and Receptor Tyrosine Kinase Signaling
Authors: Bai Longchuan , McEachern Donna , Yang Chao-Yie , Lu Jianfeng , Sun Haiying , Wang Shaomeng 
Published: January 2012

Abstract
Smac mimetics block inhibitor of apoptosis proteins to trigger TNFα-dependent apoptosis in cancer cells. However, only a small subset of cancer cells seem to be sensitive to Smac mimetics and even sensitive cells can develop resistance. Herein, we elucidated mechanisms underlying the intrinsic and acquired resistance of cancer cells to Smac mimetics. In vitro and in vivo investigations revealed that the expression of the cell surface protein LRIG1, a negative regulator of receptor tyrosine kinases (RTK), is downregulated in resistant derivatives of breast cancer cells sensitive to Smac mimetics. RNA interference–mediated downregulation of LRIG1 markedly attenuated the growth inhibitory activity of the Smac mimetic SM-164 in drug-sensitive breast and ovarian cancer cells. Furthermore, LRIG1 downregulation attenuated TNFα gene expression induced by Smac mimetics and increased the activity of multiple RTKs, including c-Met and Ron. The multitargeted tyrosine kinase inhibitors Crizotinib and GSK1363089 greatly enhanced the anticancer activity of SM-164 in all resistant cell derivatives, with the combination of SM-164 and GSK1363089 also completely inhibiting the outgrowth of resistant tumors in vivo. Together, our findings show that both upregulation of RTK signaling and attenuated TNFα expression caused by LRIG1 downregulation confers resistance to Smac mimetics, with implications for a rational combination strategy. Cancer Res; 72(5); 1229–38. ©2012 AACR.
Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements
Authors: Hayes D. Neil , Lucas Amy S. , Tanvetyanon Tawee , Krzyzanowska Monika K. , Chung Christine H. , Murphy Barbara A. , Gilbert Jill , Mehra Ranee , Moore Dominic T. , Sheikh Arif , Hoskins Janelle , Hayward Michele C. , Zhao Ni , O'Connor Wendi , Weck Karen E. , Cohen Roger B. , Cohen Ezra E.W. 
Published: January 2012

Abstract
Purpose: A multicenter, open-label, phase II trial was conducted to evaluate the efficacy, safety, and tolerability of selumetinib in iodine-refractory papillary thyroid cancer (IRPTC).
Experimental Design: Patients with advanced IRPTC with or without follicular elements and documented disease progression within the preceding 12 months were eligible to receive selumetinib at a dose of 100 mg twice daily. The primary endpoint was objective response rate using Response Evaluation Criteria in Solid Tumors. Secondary endpoints were safety, overall survival, and progression-free survival (PFS). Tumor genotype including mutations in BRAF, NRAS, and HRAS was assessed.
Results: Best responses in 32 evaluable patients out of 39 enrolled were 1 partial response (3%), 21 stable disease (54%), and 11 progressive disease (28%). Disease stability maintenance occurred for 16 weeks in 49%, 24 weeks in 36%. Median PFS was 32 weeks. BRAF V600E mutants (12 of 26 evaluated, 46%) had a longer median PFS compared with patients with BRAF wild-type (WT) tumors (33 versus 11 weeks, respectively, HR = 0.6, not significant, P = 0.3). The most common adverse events and grades 3 to 4 toxicities included rash, fatigue, diarrhea, and peripheral edema. Two pulmonary deaths occurred in the study and were judged unlikely to be related to the study drug.
Conclusions: Selumetinib was well tolerated but the study was negative with regard to the primary outcome. Secondary analyses suggest that future studies of selumetinib and other mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) inhibitors in IRPTC should consider BRAF V600E mutation status in the trial design based on differential trends in outcome. Clin Cancer Res; 18(7); 2056–65. ©2012 AACR.
Lenalidomide-Induced Immunomodulation in Multiple Myeloma: Impact on Vaccines and Antitumor Responses
Authors: Noonan Kimberly , Rudraraju Lakshmi , Ferguson Anna , Emerling Amy , Pasetti Marcela F. , Huff Carol A. , Borrello Ivan 
Published: January 2012

AbstractPurpose: To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses.Experimental Design: Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide.Results: PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ+ T cells and reductions in Th-17 cells.Conclusions: This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines. Clin Cancer Res; 18(5); 1426–34. ©2012 AACR.
Molecular and Cellular Effects of NEDD8-Activating Enzyme Inhibition in Myeloma
Authors: McMillin Douglas W. , Jacobs Hannah M. , Delmore Jake E. , Buon Leutz , Hunter Zachary R. , Monrose Val , Yu Jie , Smith Peter G. , Richardson Paul G. , Anderson Kenneth C. , Treon Steven P. , Kung Andrew L. , Mitsiades Constantine S. 
Published: January 2012

Abstract
The NEDD8-activating enzyme is upstream of the 20S proteasome in the ubiquitin/proteasome pathway and catalyzes the first step in the neddylation pathway. NEDD8 modification of cullins is required for ubiquitination of cullin-ring ligases that regulate degradation of a distinct subset of proteins. The more targeted impact of NEDD8-activating enzyme on protein degradation prompted us to study MLN4924, an investigational NEDD8-activating enzyme inhibitor, in preclinical multiple myeloma models. In vitro treatment with MLN4924 led to dose-dependent decrease of viability (EC50 = 25–150 nmol/L) in a panel of human multiple myeloma cell lines. MLN4924 was similarly active against a bortezomib-resistant ANBL-6 subline and its bortezomib-sensitive parental cells. MLN4924 had submicromolar activity (EC50 values &lt;500 nmol/L) against primary CD138+ multiple myeloma patient cells and exhibited at least additive effect when combined with dexamethasone, doxorubicin, and bortezomib against MM.1S cells. The bortezomib-induced compensatory upregulation of transcripts for ubiquitin/proteasome was not observed with MLN4924 treatment, suggesting distinct functional roles of NEDD8-activating enzyme versus 20S proteasome. MLN4924 was well tolerated at doses up to 60 mg/kg 2× daily and significantly reduced tumor burden in both a subcutaneous and an orthotopic mouse model of multiple myeloma. These studies provide the framework for the clinical investigation of MLN4924 in multiple myeloma. Mol Cancer Ther; 11(4); 942–51. ©2012 AACR.
Pro-Inflammatory Role of MicroRNA-200 in Vascular Smooth Muscle Cells From Diabetic Mice
Authors: Reddy Marpadga A. , Jin Wen , Villeneuve Louisa , Wang Mei , Lanting Linda , Todorov Ivan , Kato Mitsuo , Natarajan Rama 
Published: January 2012

Objective—
Vascular smooth muscle cells (VSMC) from type 2 diabetic db/db mice exhibit enhanced proinflammatory responses implicated in accelerated vascular complications. We examined the role of microRNA(miR)-200 family members and their target Zeb1, an E-box binding transcriptional repressor, in these events.

Methods and Results—
The expression levels of miR-200b, miR-200c, and miR-429 were increased, although protein levels of Zeb1 were decreased in VSMC and aortas from db/db mice relative to control db/+ mice. Transfection of miR-200 mimics into VSMC downregulated Zeb1 by targeting its 3′-UTR, upregulated the inflammatory genes cyclooxygenase-2 and monocyte chemoattractant protein-1, and promoted monocyte binding in db/+VSMC. In contrast, miR-200 inhibitors reversed the enhanced monocyte binding of db/dbVSMC. Zeb1 gene silencing with siRNAs also increased these proinflammatory responses in db/+VSMC confirming negative regulatory role of Zeb1. Both miR-200 mimics and Zeb1 siRNAs increased cyclooxygenase-2 promoter transcriptional activity. Chromatin immunoprecipitation showed that Zeb1 occupancy at inflammatory gene promoters was reduced in VSMC from type 2 diabetic db/db mice. Furthermore, Zeb1 knockdown increased miR-200 levels demonstrating a feedback regulatory loop.

Conclusion—
Disruption of the reciprocal negative regulatory loop between miR-200 and Zeb1 under diabetic conditions enhances proinflammatory responses of VSMC implicated in vascular complications.
Dynamic Immune Cell Accumulation During Flow-Induced Atherogenesis in Mouse Carotid Artery
Authors: Alberts-Grill Noah , Rezvan Amir , Son Dong Ju , Qiu Haiwei , Kim Chan Woo , Kemp Melissa L. , Weyand Cornelia M. , Jo Hanjoong 
Published: January 2012

Objective—
Inflammation plays a central role in atherosclerosis. However, the detailed changes in the composition and quantity of leukocytes in the arterial wall during atherogenesis are not fully understood in part because of the lack of suitable methods and animal models.

Methods and Results—
We developed a 10-fluorochrome, 13-parameter flow cytometry method to quantitate 7 major leukocyte subsets in a single digested arterial wall sample. Apolipoprotein E–deficient mice underwent left carotid artery (LCA) partial ligation and were fed a high-fat diet for 4 to 28 days. Monocyte/macrophages, dendritic cells, granulocytes, natural killer cells, and CD4 T cells significantly infiltrated the LCA as early as 4 days. Monocyte/macrophages and dendritic cells decreased between 7 and 14 days, whereas T-cell numbers remained steady. Leukocyte numbers peaked at 7 days, preceding atheroma formation at 14 days. B cells entered LCA by 14 days. Control right carotid and sham-ligated LCAs showed no significant infiltrates. Polymerase chain reaction and ELISA arrays showed that expression of proinflammatory cytokines and chemokines peaked at 7 and 14 days postligation, respectively.

Conclusion—
This is the first quantitative description of leukocyte number and composition over the life span of murine atherosclerosis. These results show that disturbed flow induces rapid and dynamic leukocyte accumulation in the arterial wall during the initiation and progression of atherosclerosis.