bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilateral Bone‐Anchored Hearing Aids for Bilateral Permanent Conductive Hearing Loss
Authors: Janssen Renée M. , Hong Paul , Chadha Neil K. 
Published: June 2012

ObjectiveTo systematically review the outcomes of bilateral versus unilateral bone‐anchored hearing aids (BAHA) for individuals with bilateral permanent conductive hearing loss (CHL) with the goal of (1) deriving clinically oriented insights into the advantages and disadvantages of bilateral fitting and (2) identifying gaps in knowledge to stimulate future research.Data SourcesMedline, EMBASE, and Cochrane databases were searched for studies of all languages published between 1977 and July 2011.Review MethodsStudies were included if subjects of any age had permanent bilateral CHL and bilateral implanted BAHAs. Outcome measures of interest were any subjective or objective audiologic measures, quality of life indicators, or reports of adverse events.ResultsIn all, 628 abstracts were generated from the literature searches; 11 studies met the criteria for data extraction and analysis. All 11 studies were observational. In most studies, comparisons between unilateral and bilateral BAHA were intra‐subject. Bilateral BAHA provided audiologic benefit compared to unilateral BAHA (improved thresholds for tones [2 studies], speech in quiet [5 studies] and in noise [3 studies], and improved localization/lateralization [3 studies]) and patients’ perceived subjective benefit from bilateral BAHA (3 studies). Disadvantages of bilateral BAHAs included listening in noise in some conditions (3 studies), presumed additional cost, and presumed increase in adverse event risk.ConclusionBilateral BAHA provided additional objective and subjective benefit compared to unilateral BAHA; however, there was a limited number of studies available with good quality evidence. Aspects of bilateral BAHA that would benefit from further investigation are described, and recommendations for bilateral BAHA candidacy criteria are provided.
Effect of Continuous Positive Airway Pressure on C‐reactive Protein Levels in Sleep Apnea
Authors: Friedman Michael , Samuelson Christian G. , Hamilton Craig , Fisher Michelle , Kelley Kanwar , Joseph Ninos J. , Wang Pa‐Chun , Lin Hsin‐Ching 
Published: June 2012

ObjectiveEvaluate the effects of continuous positive airway pressure (CPAP) on C‐reactive protein (CRP) levels, reported either as a primary or secondary end point among patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS) based on a meta‐analysis of published studies.Data SourcesEnglish‐language searches of PubMed, Ovid, and the Cochrane databases were completed. Reference sections of identified studies were also examined for additional relevant articles to review.Review MethodsStudies of adult patients with OSAHS who reported pre‐ and post‐CPAP treatment CRP were reviewed and analyzed. Two independent reviewers extracted data from 10 peer‐reviewed studies, which were combined using a random effects meta‐analysis model.ResultsThe CPAP treatment was found to lead to a significant reduction in CRP levels (17.8%, P =. 002). This corresponds to an effect size of −0.485 (−0.731, −0.240). Sensitivity analysis was done to determine the impact of study design. Both case‐control studies and case‐series studies yielded a significant effect. Sensitivity analysis also yielded a significant effect for studies with average body mass index <30, studies where CPAP was employed over automatic positive airway pressure, and studies treating patients ≤3 months. Analysis of publication bias, however, revealed a likelihood of “missing” studies.ConclusionAlthough there is a significant lack of high‐quality studies addressing this question, this analysis suggests that treatment with CPAP leads to a statistically significant reduction in CRP levels. However, the mean pre‐ and posttreatment CRP levels observed are considered “high risk” for cardiovascular morbidity. The clinical significance of this finding as it relates to cardiovascular risk reduction and the relationship between CRP and OSAHS requires further study.
In vitro evaluation of quaternized polydimethylaminoethylmethacrylate sub-microparticles for oral insulin delivery
Authors: Sonia TA , Sharma Chandra P 
Published: June 2012

This investigation describes the synthesis and in vitro evaluation of cationic hydrogel sub-microparticles based on polydimethylaminoethylmethacrylate for oral insulin delivery. Polymerization of dimethylaminoethylmethacrylate was carried out in aqueous medium with potassium persulfate as the initiator. Quaternization of the resulting hydrogel was carried out to introduce cationic surface groups and the derivatization was confirmed by zeta potential measurements, nuclear magnetic resonance and infrared spectroscopies. Swelling behavior of these particles was evaluated for dependence of pH. Insulin-loaded particles were subjected to in vitro release experiments at gastric and intestinal pH. Moreover, cytotoxicity evaluation showed that both polydimethylaminoethylmethacrylate and its quaternized derivative were non-toxic to Caco-2 and L929 cell lines. The presence of quaternary ammonium groups improved the cationic charge and enhanced the mucoadhesive properties of the hydrogel. Confocal microscopic observations showed that these sub-microparticles were capable of opening tight junctions between the Caco-2 cells and thus increased the paracellular permeability. The above studies suggest that cationic hydrogel sub-microparticles can act as a good candidate for oral insulin delivery.
CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte
Authors: Delarue Richard , Haioun Corinne , Ribrag Vincent , Brice Pauline , Delmer Alain , Tilly Herve , Salles Gilles , Van Hoof Achiel , Casasnovas Olivier , Brousse Nicole , Lefrere Francois , Hermine Olivier 
Published: June 2012

Abstract
Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase 2 trial using cytarabine and rituximab as induction regimen before autologous stem cell transplantation. Patients younger than 66 years with stage 3 or 4 MCL were included. Treatment consisted of 3 courses of CHOP21 with rituximab at the third one and 3 of R-DHAP. Responding patients were eligible for autologous stem cell transplantation with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, Performance Status > 16%, lactate dehydrogenase > 1N 38%, Mantle Cell Lymphoma International Prognostic Index (low 55%, intermediate 38%, high 13%). The overall response rate was 93% after (R)-CHOP and 95% after R-DHAP. Although uncommon after (R)-CHOP (12%), 57% of patients were in complete response after R-DHAP. With median follow-up of 67 months, median event-free survival is 83 months, and median overall survival is not reached. Five-year overall survival is 75%. Comparison with a previous study without rituximab shows improvement of outcome (median event-free survival, 51 vs 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with rituximab and cytarabine-based regimens is safe and effective in MCL patients. This regimen is currently compared with R-CHOP21 induction in a multicentric European protocol.
CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis
Authors: Jiang Tianxia , Zhuang Jie , Duan Hongxia , Luo Yongting , Zeng Qiqun , Fan Kelong , Yan Huiwen , Lu Di , Ye Zhongde , Hao Junfeng , Feng Jing , Yang Dongling , Yan Xiyun 
Published: June 2012

AbstractCD146 is a novel endothelial biomarker and plays an essential role in angiogenesis; however, its role in the molecular mechanism underlying angiogenesis remains poorly understood. In the present study, we show that CD146 interacts directly with VEGFR-2 on endothelial cells and at the molecular level and identify the structural basis of CD146 binding to VEGFR-2. In addition, we show that CD146 is required in VEGF-induced VEGFR-2 phosphorylation, AKT/p38 MAPKs/NF-κB activation, and thus promotion of endothelial cell migration and microvascular formation. Furthermore, we show that anti-CD146 AA98 or CD146 siRNA abrogates all VEGFR-2 activation induced by VEGF. An in vivo angiogenesis assay showed that VEGF-promoted microvascular formation was impaired in the endothelial conditional knockout of CD146 (CD146EC-KO). Our animal experiments demonstrated that anti-CD146 (AA98) and anti-VEGF (bevacizumab) have an additive inhibitory effect on xenografted human pancreatic and melanoma tumors. The results of the present study suggest that CD146 is a new coreceptor for VEGFR-2 and is therefore a promising target for blocking tumor-related angiogenesis.
The B subunits of Shiga-like toxins induce regulated VWF secretion in a phospholipase D1–dependent manner
Authors: Huang Jing , Haberichter Sandra L. , Sadler J. Evan 
Published: June 2012

AbstractShiga toxin (Stx) causes diarrhea-associated hemolytic uremic syndrome by damaging renal microvascular endothelium. The pentameric B subunits of Stx types 1 and 2 (Stx1B and Stx2B) are sufficient to stimulate acute VWF secretion from endothelial cells, but Stx1B and Stx2B exert distinct effects on Ca2+ and cAMP pathways. Therefore, we investigated other signaling components in StxB-induced VWF exocytosis. Incubation of HUVECs with StxB transiently increased phospholipase D (PLD) activity. Inhibition of PLD activity or shRNA-mediated PLD1 knockdown abolished StxB-induced VWF secretion. In addition, treatment with StxB triggered actin polymerization, enhanced endothelial monolayer permeability, and activated RhoA. PLD activation and VWF secretion induced by Stx1B were abolished on protein kinase Cα (PKCα) inhibition or gene silencing but were only moderately reduced by Rho or Rho kinase inhibitors. Conversely, PLD activation and VWF exocytosis induced by Stx2B were reduced by Rho/Rho kinase inhibitors and dominant-negative RhoA, whereas attenuation of PKCα did not affect either process. Another PLD1 activator, ADP-ribosylation factor 6, was involved in VWF secretion induced by Stx1B or Stx2B, but not histamine. These data indicate that Stx1B and Stx2B induce acute VWF secretion in a PLD1-dependent manner but do so by differentially modulating PKCα, RhoA, and ADP-ribosylation factor 6.
A novel splice variant of folate receptor 4 predominantly expressed in regulatory T cells
Authors: Tian Yi , Wu Guoqiang , Xing Jun-Chao , Tang Jun , Zhang Yi , Huang Ze-Min , Jia Zheng-Cai , Zhao Ren , Tian Zhi-Qiang , Wang Shu-Feng , Chen Xiao-Ling , Wang Li , Wu Yu-Zhang , Ni Bing 
Published: June 2012

Abstract

Background
Regulatory T cells (Tregs) are required for proper maintenance of immunological self-tolerance and immune homeostasis. Folate receptor 4 (FR4) is expressed at high levels in transforming growth factor-beta (TGF-β)-induced Tregs and natural Tregs. Moreover, antibody-mediated targeting of FR4 is sufficient to mediate Treg depletion.

Results
In this study, we describe a novel FR4 transcript variant, FR4D3, in which exon 3 is deleted. The mRNA of FR4D3 encodes a FR4 variant truncated by 189 bp. FR4D3 was found to be predominantly expressed in CD4+CD25+ Treg cells. Overexpression of FR4D3 in CD4+CD25+ Treg cells in vitro stimulated proliferation, which may modulate the ability of these cells to bind and incorporate folic acid.

Conclusions
Our results suggested that high levels of FR4D3 may be critical to support the substantial proliferative capacity of Treg cells.
Aspergillus flavus grown in peptone as the carbon source exhibits spore density- and peptone concentration-dependent aflatoxin biosynthesis
Authors: Yan Shijuan , Liang Yating , Zhang Jindan , Liu Chun-Ming 
Published: June 2012

Abstract
Background
Aflatoxins (AFs) are highly carcinogenic compounds produced by Aspergillus species in seeds with high lipid and protein contents. It has been known for over 30 years that peptone is not conducive for AF productions, although reasons for this remain unknown.

Results
In this study, we showed that when Aspergillus flavus was grown in peptone-containing media, higher initial spore densities inhibited AF biosynthesis, but promoted mycelial growth; while in glucose-containing media, more AFs were produced when initial spore densities were increased. This phenomenon was also observed in other AF-producing strains including A. parasiticus and A. nomius. Higher peptone concentrations led to inhibited AF production, even in culture with a low spore density. High peptone concentrations did however promote mycelial growth. Spent medium experiments showed that the inhibited AF production in peptone media was regulated in a cell-autonomous manner. mRNA expression analyses showed that both regulatory and AF biosynthesis genes were repressed in mycelia cultured with high initial spore densities. Metabolomic studies revealed that, in addition to inhibited AF biosynthesis, mycelia grown in peptone media with a high initial spore density showed suppressed fatty acid biosynthesis, reduced tricarboxylic acid (TCA) cycle intermediates, and increased pentose phosphate pathway products. Additions of TCA cycle intermediates had no effect on AF biosynthesis, suggesting the inhibited AF biosynthesis was not caused by depleted TCA cycle intermediates.

Conclusions
We here demonstrate that Aspergillus species grown in media with peptone as the sole carbon source are able to sense their own population densities and peptone concentrations to switch between rapid growth and AF production. This switching ability may offer Aspergillus species a competition advantage in natural ecosystems, producing AFs only when self-population is low and food is scarce.
The aberrant asynchronous replication — characterizing lymphocytes of cancer patients — is erased following stem cell transplantation
Authors: Nagler Arnon , Cytron Samuel , Mashevich Maya , Korenstein-Ilan Avital , Avivi Lydia 
Published: June 2012

Abstract

Background
Aberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy levels in cells of patients with haematological malignancies from diagnosis to full remission, as achieved by allogeneic stem cell transplantation (alloSCT).

Methods

TP53 (a tumor suppressor gene assigned to chromosome 17), AML1 (a gene assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 translocation) and the pericentomeric satellite sequence of chromosome 17 (CEN17) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosomes 17 and 21. Replication timing and aneuploidy were detected cytogenetically using fluorescence in situ hybridization (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes.

Results
We show that aberrant epigenetic markers are detected in patients with hematological malignancies from the time of diagnosis through to when they are scheduled to undergo alloSCT. These aberrations are unaffected by the clinical status of the disease and are displayed both during accelerated stages as well as in remission. Yet, these markers are eradicated completely following stem cell transplantation. In contrast, the increased levels of aneuploidy (irreversible genetic alterations) displayed in blood lymphocytes at various stages of disease are not eliminated following transplantation. However, they do not elevate and remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, applied in vitro to lymphocytes of patients prior to transplantation mimics the effect of transplantation: the epigenetic aberrations disappear while aneuploidy stays unchanged.

Conclusions
The reversible nature of the replication aberrations may serve as potential epigenetic blood markers for evaluating the success of transplant or other treatments and for long-term follow up of the patients who have overcome a hematological malignancy.
Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome
Authors: Xu Jia , Shetty Priya B , Feng Weiwei , Chenault Carol , Bast Robert C , Issa Jean-Pierre J , Hilsenbeck Susan G , Yu Yinhua 
Published: June 2012

Abstract

Background
Aberrant promoter CpG island hypermethylation is associated with transcriptional silencing. Tumor suppressor genes are the key targets of hypermethylation in breast cancer and therefore may lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified correlated methylation of two pairs of genes - HIN-1/RASSFIA and RIL/CDH13 - with expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 (HER2). To determine the impact of methylation on clinical outcome, we have conducted a larger study with breast cancers for which time to first recurrence and overall survival are known.

Methods
Tumors from 193 patients with early stage breast cancer who received no adjuvant systemic therapy were used to analyze methylation levels of RIL, HIN-1, RASSF1A and CDH13 genes for associations with known predictive and prognostic factors and for impact on time to first recurrence and overall survival.

Results
In this study, we found that ER was associated with RASSF1A methylation (p < 0.001) and HIN-1 methylation (p = 0.002). PR was associated with RIL methylation (p = 0.012), HIN-1 (p = 0.002), and RASSF1A methylation (p = 0.019). Tumor size was associated with RIL and CDH13 methylation (both p = 0.002), and S-phase was associated with RIL methylation (p = 0.036). Only RASSF1A was associated with worse time to first recurrence (p = 0.045) and worse overall survival (p = 0.016) after adjusting for age, tumor size, S-phase, estrogen receptor and progesterone receptor.

Conclusions
Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancers was associated with clinical characteristics, but only RASSF1A methylation was associated with time to first recurrence and overall survival. Our data suggest that RASSF1A methylation could be a potential prognostic biomarker.
Methylation signature of lymph node metastases in breast cancer patients
Authors: Barekati Zeinab , Radpour Ramin , Lu Qing , Bitzer Johannes , Zheng Hong , Toniolo Paolo , Lenner Per , Zhong Xiao Yan 
Published: June 2012

Abstract

Background
Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers.

Methods
The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Results
The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis.

Conclusions
The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.
Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
Authors: Hisatomi Keiko , Mukae Hiroshi , Sakamoto Noriho , Ishimatsu Yuji , Kakugawa Tomoyuki , Hara Shintaro , Fujita Hanako , Nakamichi Seiko , Oku Hisashi , Urata Yoshishige , Kubota Hiroshi , Nagata Kazuhiro , Kohno Shigeru 
Published: June 2012

Abstract

Background
Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro.

Methods
The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining.

Results
TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1.

Conclusion
We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.