bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation
Authors: Fairus Syed , Nor Rosnah M , Cheng Hwee M , Sundram Kalyana 
Published: January 2012

Abstract

Background
Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.

Methods
Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.

Results
After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.

Conclusions
Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.
Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction
Authors: Wang Wen-Ping , Wang Kang-Ning , Gao Qiang , Chen Long-Qi 
Published: January 2012

Abstract

Background
The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.

Methods
From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.

Results
In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.

Conclusions
Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.
Complications as indicators of quality assurance after 401 consecutive colorectal cancer resections: the importance of surgeon volume in developing colorectal cancer units in India
Authors: Shetty Guruprasad S , Bodhankar Yashodhan D , Ingle Sachin , Thakkar Rohan G , Goel Mahesh , Shukla Parul J , Shrikhande Shailesh V 
Published: January 2012

Abstract

Background
The low incidence of colorectal cancer in India, coupled with absence of specialized units, contribute to lack of relevant data arising from the subcontinent. We evaluated the data of the senior author to better define the requirements that would enable development of specialized units in a country where colorectal cancer burden is increasing.

Methods
We retrospectively analyzed data of 401 consecutive colorectal resections from a prospective database of the senior author. In addition to patient demographics and types of resections, perioperative data like intraoperative blood loss, duration of surgery, complications, re-operation rates and hospital stay were recorded and analyzed.

Results
The median age was 52 years (10-86 years). 279 were males and 122 were females. The average duration of surgery was 220.32 minutes (range 50 - 480 min). The overall complication rate was 12.2% (49/401) with a 1.2% (5/401) mortality rate. The patients having complications had an increase in their median hospital stay (from 10.5 days to 23.4 days) and the re-operation rate in them was 51%. The major complications were anastomotic leaks (2.5%) and stoma related complications (2.7%).

Conclusions
This largest ever series from India compares favorably with global standards. In a nation where colorectal cancer is on the rise, it is imperative that high volume centers develop specialized units to train future specialist colorectal surgeons. This would ensure improved quality assurance and delivery of health care even to outreach, low volume centers.
Gelatin-layered and multi-sized porous β-tricalcium phosphate for tissue engineering scaffold
Authors: Kim Sung-Min , Yi Soon-Aei , Choi Seong-Ho , Kim Kwang-Mahn , Lee Yong-Keun 
Published: January 2012

Abstract
The multi-sized porous β-tricalcium phosphate scaffolds were fabricated by freeze drying followed by slurry coating using a multi-sized porous sponge as a template. Then, gelatin was dip coated on the multi-sized porous β-tricalcium phosphate scaffolds under vacuum. The mechanical and biological properties of the fabricated scaffolds were evaluated and compared to the uniformly sized porous scaffolds and scaffolds that were not coated by gelatin. The compressive strength was tested by a universal testing machine, and the cell viability and differentiation behavior were measured using a cell counting kit and alkaline phosphatase activity using the MC3T3-E1 cells. In comparison, the gelatin-coated multi-sized porous β-tricalcium phosphate scaffold showed enhanced compressive strength. After 14 days, the multi-sized pores were shown to affect cell differentiation, and gelatin coatings were shown to affect the cell viability and differentiation. The results of this study demonstrated that the multi-sized porous β-tricalcium phosphate scaffold coated by gelatin enhanced the mechanical and biological strengths.
Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes
Authors: Yang Chuen-Mao , Lin Chih-Chung , Lee I-Ta , Lin Yi-Hsin , Yang Caleb M , Chen Wei-June , Jou Mei-Jie , Hsiao Li-Der 
Published: January 2012

Abstract

Background
Japanese encephalitis virus (JEV) infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS) cells, including astrocytes and neurons. Matrix metalloproteinase (MMP)-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB) and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) are largely unclear.

Methods
In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos), c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs.

Results
Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone), c-Src (PP1), PDGFR (AG1296), and PI3K (LY294002), and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs.

Conclusion
From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases.
Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection
Authors: Chen En-Qiang , Sun Hui , Feng Ping , Gong Dao-Yin , Liu Cong , Bai Lang , Yang Wen-Bing , Lei Xue-Zhong , Chen Li-Yu , Huang Fei-Jun , Tang Hong 
Published: January 2012

Abstract
Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3β with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3β expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3β was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB
Programmed cell death in type II neuroblast lineages is required for central complex development in the Drosophila brain
Authors: Jiang Yanrui , Reichert Heinrich 
Published: January 2012

Abstract

Background
The number of neurons generated by neural stem cells is dependent upon the regulation of cell proliferation and by programmed cell death. Recently, novel neural stem cells that amplify neural proliferation through intermediate neural progenitors, called type II neuroblasts, have been discovered, which are active during brain development in Drosophila. We investigated programmed cell death in the dorsomedial (DM) amplifying type II lineages that contribute neurons to the development of the central complex in Drosophila, using clonal mosaic analysis with a repressible cell marker (MARCM) and lineage-tracing techniques.

Results
A significant number of the adult-specific neurons generated in these DM lineages were eliminated by programmed cell death. Programmed cell death occurred during both larval and pupal stages. During larval development, approximately one-quarter of the neuronal (but not glial) cells in the lineages were eliminated by apoptosis before the formation of synaptic connectivity during pupal stages. Lineage-tracing experiments documented the extensive contribution of intermediate neural progenitor-containing DM lineages to all of the major modular substructures of the adult central complex. Moreover, blockage of apoptotic cell death specifically in these lineages led to prominent innervation defects of DM-derived neural progeny in the major neuropile substructures of the adult central complex.

Conclusions
Our findings indicate that significant neural overproliferation occurs normally in type II DM lineage development, and that elimination of excess neurons in these lineages through programmed cell death is required for the formation of correct neuropile innervation in the developing central complex. Thus, amplification of neuronal proliferation through intermediate progenitors and reduction of neuronal number through programmed cell death operate in concert in type II neural stem-cell lineages during brain development.
Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia
Authors: da Cunha Ribeiro Roberta Potenza , Roschel Hamilton , Artioli Guilherme Gianini , Dassouki Thalita , Perandini Luiz Augusto , Calich Ana Luisa , de Sá Pinto Ana Lúcia , Lima Fernanda Rodrigues , Bonfá Eloísa , Gualano Bruno 
Published: January 2012

Abstract

Introduction

We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI).

Methods

Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test.

Results

FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM.

Conclusions

Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.
Hyperuricemia and untreated gout are poor prognostic markers among those with a recent acute myocardial infarction
Authors: Krishnan Eswar , Pandya Bhavik J , Lingala Bharathi , Hariri Ali , Dabbous Omar 
Published: January 2012

Abstract
Introduction
Patients with a history of myocardial infarction (MI) are often at risk for complications, including subsequent MI and death. Use of prognostic markers may aid in preventing these poor outcomes. Hyperuricemia is associated with increased risk for coronary heart disease (CHD) and/or mortality; however, it is unknown if serum urate (sUA) levels predict outcomes in patients with previous MI. The purpose of this study was to assess hyperuricemia as a biomarker of CHD outcomes in such patients.

Methods
These were post hoc analyses of datasets from the Aspirin Myocardial Infarction Study, a 1:1 randomized, double-blind clinical trial, conducted from 1975 to 1979, that examined mortality rates following daily aspirin administration over three years in individuals with documented MI. The primary outcome measures were all-cause death, CHD mortality, coronary incidence, and stroke by quartile of baseline sUA. A sub-analysis of all outcome measures in the presence or absence of gouty arthritis was also performed.

Results
Of 4,524 enrolled participants, data on 4,352 were analyzed here. All outcomes were greatest for patients in the fourth sUA quartile. In multivariate regression models, the hazard ratios (HR) for patients in the highest quartile were 1.88 for all-cause mortality (95% confidence interval (CI), 1.45 to 2.46), 1.99 for CHD mortality (95% CI, 1.49 to 2.66), and 1.36 for coronary incidence (95% CI, 1.08 to 1.70). Participants with untreated gout had an adjusted hazard ratio ranging from 1.5 to 2.0 (all P < 0.01) for these outcomes. Participants with gout who were receiving treatment did not exhibit this additional risk.

Conclusions
sUA and untreated gout may be independent prognostic markers for poor all-cause and CHD mortality in patients with recent acute MI.
Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial
Authors: Fleishaker Dona L , Garcia Meijide Juan A , Petrov Andriy , Kohen Michael David , Wang Xin , Menon Sujatha , Stock Thomas C , Mebus Charles A , Goodrich James M , Mayer Howard B , Zeiher Bernhardt G 
Published: January 2012

Abstract

Introduction

The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).

Methods

This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.

Results

Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).

Conclusions

Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.

Trial Registration

ClinicalTrials.gov: NCT00427934
A longitudinal study of the association between dietary factors, serum lipids, and bone marrow lesions of the knee
Authors: Doré Dawn , de Hoog Jonathon , Giles Graham , Ding Changhai , Cicuttini Flavia , Jones Graeme 
Published: January 2012

Abstract
Introduction
Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs.

Methods
In total, 394 older men and women (mean age, 63 years; range, 52 to 79) were measured at baseline and approximately 2.7 years later. BMLs were determined by using T2-weighted fat-saturation magnetic resonance imaging (MRI) by measuring the maximal area of the lesion. Nutrient intake (total energy, fat, carbohydrate, protein, and sugar) and serum lipids were assessed at baseline.

Results
Cross-sectionally, dietary factors and lipids were not significantly associated with BMLs. Energy, carbohydrate, and sugar intake (but not fat) were positively associated with a change in BML size (β = 15.44 to 19.27 mm2 per 1 SD increase; all P < 0.05). High-density lipoprotein (HDL) cholesterol tended to be negatively associated with BML change (β = -11.66 mm2 per 1 SD increase; P = 0.088).

Conclusions
Energy, carbohydrate, and sugar intake may be risk factors for BML development and progression. HDL cholesterol seems protective against BMLs. These results suggest that macronutrients and lipids may be important in BML etiology and that dietary modification may alter BML natural history.
Evaluation of a Breast Cancer Nomogram for Predicting Risk of Ipsilateral Breast Tumor Recurrences in Patients With Ductal Carcinoma in Situ After Local Excision
Authors: Yi Min , Meric-Bernstam Funda , Kuerer Henry M. , Mittendorf Elizabeth A. , Bedrosian Isabelle , Lucci Anthony , Hwang Rosa F. , Crow Jaime R. , Luo Sheng , Hunt Kelly K. 
Published: January 2012

Purpose Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution. Patients and Methods We retrospectively identified 794 patients with a diagnosis of DCIS who had undergone local excision from 1990 through 2007 at the MD Anderson Cancer Center (MDACC). Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients who had complete data. Results There was a marked difference with respect to tumor grade, prevalence of necrosis, initial presentation, final margins, and receipt of endocrine therapy between the two cohorts. The biggest difference was that more patients received radiation in the MDACC cohort (75% at MDACC v 49% at MSKCC; P < .001). Follow-up time in the MDACC cohort was longer than in the MSKCC cohort (median 7.1 years v 5.6 years), and the recurrence rate was lower in the MDACC cohort (7.9% v 11%). The median 5-year probability of recurrence was 5%, and the median 10-year probability of recurrence was 7%. The nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated imperfect calibration and discrimination, with a concordance index of 0.63. Conclusion Predictive models for IBTR in patients with DCIS who were treated with local excision are imperfect. Our current ability to accurately predict recurrence on the basis of clinical parameters alone is limited.
Meta-Analysis of Psychosocial Interventions to Reduce Pain in Patients With Cancer
Authors: Sheinfeld Gorin Sherri , Krebs Paul , Badr Hoda , Janke Elizabeth Amy , Jim Heather S.L. , Spring Bonnie , Mohr David C. , Berendsen Mark A. , Jacobsen Paul B. 
Published: January 2012

Purpose Pain is one of the most common, burdensome, and feared symptoms experienced by patients with cancer. American Pain Society standards for pain management in cancer recommend both pharmacologic and psychosocial approaches. To obtain a current, stable, and comprehensive estimate of the effect of psychosocial interventions on pain—an important clinical topic—we conducted a meta-analysis of randomized controlled studies among adult patients with cancer published between 1966 and 2010. Methods Three pairs of raters independently reviewed 1,681 abstracts, with a systematic process for reconciling disagreement, yielding 42 papers, of which 37 had sufficient data for meta-analysis. Studies were assessed for quality using a modified seven-item Physiotherapy Evidence Database (PEDro) coding scheme. Pain severity and interference were primary outcome measures. Results Study participants (N = 4,199) were primarily women (66%) and white (72%). The weighted averaged effect size across studies for pain severity (38 comparisons) was 0.34 (95% CI, 0.23 to 0.46; P < .001), and the effect size for pain interference (four comparisons) was 0.40 (95% CI, 0.21 to 0.60; P < .001). Studies that monitored whether treatment was delivered as intended had larger effects than those that did not (P = .04). Conclusion Psychosocial interventions had medium-size effects on both pain severity and interference. These robust findings support the systematic implementation of quality-controlled psychosocial interventions as part of a multimodal approach to the management of pain in patients with cancer.