bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of nuclear factor κ B expression in patients with advanced cervical cancer undergoing radiation therapy followed by hysterectomy
Authors: Baiocchi Glauco , Begnami Maria Dirlei , Fukazawa Elza Mieko , Oliveira Renato Almeida Rosa , Faloppa Carlos Chaves , Kumagai Lillian Yuri , Badiglian-Filho Levon , Pellizzon Antonio Cassio Assis , Maia Maria Aparecida Conte , Jacinto Alexandre Arthur , Soares Fernando Augusto , Lopes Ademar 
Published: March 2012

AimsThe nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker.MethodsA retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy.Results16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death.ConclusionsThese data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.
Trainers' perceptions of the direct observation of practical skills assessment in histopathology training: a qualitative pilot study
Authors: Finall Alison 
Published: March 2012

AimsThis pilot study of the direct observation of practical skills (DOPS) assessment of histopathology trainees is needed in the absence of existing information on histopathology in the UK. The aim of the study was to explore the experiences and perceptions of trainers in using the DOPS tool with histopathology trainees.MethodsA qualitative approach was taken using paper-based questionnaires to consultants in a single teaching hospital histopathology department.ResultsDOPS was perceived by all trainers as a valid form of assessment. There was a spread of opinion regarding its feasibility, with some respondents raising concern about its impact on time. 28% of respondents were doubtful about the formative nature of DOPS. All stated the assessment was fair.ConclusionsThemes that have emerged include concerns about impact on trainer time, whether DOPS is used in a formative manner and concerns about the amount of guidance provided to trainers. Further research is required to expand on these points.
Utility of multispectral imaging in automated quantitative scoring of immunohistochemistry
Authors: Fiore Christopher , Bailey Dyane , Conlon Niamh , Wu Xiaoqiu , Martin Neil , Fiorentino Michelangelo , Finn Stephen , Fall Katja , Andersson Swen-Olof , Andren Ove , Loda Massimo , Flavin Richard 
Published: March 2012

BackgroundAutomated scanning devices and image analysis software provide a means to overcome the limitations of manual semiquantitative scoring of immunohistochemistry. Common drawbacks to automated imaging systems include an inability to classify tissue type and an inability to segregate cytoplasmic and nuclear staining.MethodsImmunohistochemistry for the membranous marker α-catenin, the cytoplasmic marker stathmin and the nuclear marker Ki-67 was performed on tissue microarrays (TMA) of archival formalin-fixed paraffin-embedded tissue comprising 471 (α-catenin and stathmin) and 511 (Ki-67) cases of prostate adenocarcinoma. These TMA were quantitatively analysed using two commercially available automated image analysers, the Ariol SL-50 system and the Nuance system from CRi. Both systems use brightfield microscopy for automated, unbiased and standardised quantification of immunohistochemistry, while the Nuance system has spectral deconvolution capabilities.ResultsOverall concordance between scores from both systems was excellent (r=0.90; 0.83–0.95). The software associated with the multispectral imager allowed accurate automated classification of tissue type into epithelial glandular structures and stroma, and a single-step segmentation of staining into cytoplasmic or nuclear compartments allowing independent evaluation of these areas. The Nuance system, however, was not able to distinguish reliably between tumour and non-tumour tissue. In addition, variance in the labour and time required for analysis between the two systems was also noted.ConclusionDespite limitations, this study suggests some beneficial role for the use of a multispectral imaging system in automated analysis of immunohistochemistry.
Mechanisms of Ploidy Increase in Human Cancers: A New Role for Cell Cannibalism
Authors: Krajcovic Matej , Overholtzer Michael 
Published: March 2012

AbstractAneuploidy is a hallmark of human cancers originating from abnormal mitoses. Many aneuploid cancer cells also have greater-than-diploid DNA content, suggesting that polyploidy is a common precursor to aneuploidy during tumor progression. Polyploid cells can originate from cell fusion, endoreplication, and cytokinesis failure. Recently we found that cell cannibalism by entosis, a form of cell engulfment involving live cells, also leads to polyploidy, as internalized cells disrupt cytokinesis of their engulfing cell hosts. By this mechanism, cannibalistic cell behavior could promote tumor progression by leading to aneuploidy. Here, we discuss cell cannibalism in cancer and other mechanisms that result in the formation of polyploid cancer cells. Cancer Res; 72(7); 1596–601. ©2012 AACR.
Food Hypersensitivity and Otolaryngologic Conditions in Young Children
Authors: Paddack Angela , Gibbons Troy , Smith Chandra , Patil Sowmya , Richter Gresham T. 
Published: March 2012

Objectives/HypothesisTo explore the relationship between food hypersensitivity and common upper aerodigestive disorders found in children younger than 2 years.Study DesignCase control study.SettingTertiary pediatric gastroenterology/otolaryngology clinics.MethodsTwo‐year retrospective chart review of a common cohort of children younger than 2 years with suspected cow’s milk protein allergy (CMPA). Patients were managed in both a tertiary pediatric gastroenterology and otolaryngology clinic and compared with a control study group.ResultsOne hundred ninety‐one children with CMPA were reviewed. One hundred forty‐one had aerodigestive complaints, with 101 having sufficient follow‐up to participate in the study. Ninety‐one percent of this final patient group demonstrated improved symptoms following dairy elimination. Twenty‐five patients (27%) had associated otolaryngologic (ear, nose, and throat [ENT]) issues that had been refractory to maximal gastroesophageal reflux therapy. The most common associated upper aerodigestive conditions were persistent upper airway congestion (72%) and oropharyngeal dysphagia (80%). Sixty percent of ENT disease improved with elimination diet. Eosinophilic esophagitis was noted in 36% of the cohort who had mucosal biopsies performed. Otolaryngology intervention was much more common in the cohort of children with CMPA compared with controls (odds ratio, 33.78; 95% confidence interval, 7.55, 151.03).ConclusionsCMPA is difficult to diagnose because of limited accurate diagnostic tools, especially in young children. This study suggests a relationship between CMPA and otolaryngologic conditions in children younger than 2 years. Some patients in this study showed symptom improvement via an elimination diet. Early recognition of otolaryngologic manifestations of CMPA may help manage this condition in young children.
Sialocele after Parotid Surgery
Authors: Herbert Hayley A. , Morton Randall P. 
Published: March 2012

ObjectiveTo assess possible factors contributing to the occurrence of a sialocele after parotid surgery.Study DesignCase series with chart review.SettingSecondary otolaryngology service.MethodsOne hundred two consecutive parotid operations by 1 surgeon were recorded. A high rate of sialocele formation was addressed by identifying possible contributing factors, sequentially introducing changes, and then analyzing the effect of such changes.ResultsTwenty patients developed a sialocele (19.6%). Demographic variables of those who developed a sialocele were similar to those who did not. Factors examined included partial versus complete superficial parotidectomy, use of Surgicel, vacuum drain pressure, and postoperative duration for surgical drain. The only significant factor on regression analysis for increasing the risk of a sialocele development was the use of Surgicel (P =. 023). Once the use of Surgicel stopped, the rate of sialocele formation diminished markedly (from 28.6% to 11.3%).ConclusionsSialocele can cause significant problems for the patient and surgeon in terms of delayed wound healing and increased clinic resources and frustration. This study suggests that the use of products such as Surgicel increases the risk of postoperative sialocele formation.
Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth
Authors: Abéngozar María Angeles , de Frutos Sergio , Ferreiro Sergio , Soriano Joaquím , Perez-Martinez Manuel , Olmeda David , Marenchino Marco , Cañamero Marta , Ortega Sagrario , Megias Diego , Rodriguez Antonio , Martínez-Torrecuadrada Jorge L. 
Published: March 2012

Abstract
Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathologic conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, 2 highly specific human single-chain Fv (scFv) Ab fragments against ephrinB2 were generated and characterized. Both Ab fragments suppressed endothelial cell migration and tube formation in vitro in response to VEGF and provoked abnormal cell motility and actin cytoskeleton alterations in isolated endothelial cells. As only one of them (B11) competed for binding of ephrinB2 to EphB4, these data suggest an EphB-receptor–independent blocking mechanism. Anti-ephrinB2 therapy reduced VEGF-induced neovascularization in a mouse Matrigel plug assay. Moreover, systemic administration of ephrinB2-blocking Abs caused a drastic reduction in the number of blood and lymphatic vessels in xenografted mice and a concomitant reduction in tumor growth. Our results show for the first time that specific Ab-based ephrinB2 targeting may represent an effective therapeutic strategy to be used as an alternative or in combination with existing antiangiogenic drugs for treating patients with cancer and other angiogenesis-related diseases.
Adaptive evolution and functional constraint at TLR4 during the secondary aquatic adaptation and diversification of cetaceans
Authors: Shen Tong , Xu Shixia , Wang Xiaohong , Yu Wenhua , Zhou Kaiya , Yang Guang 
Published: March 2012

Abstract

Background
Cetaceans (whales, dolphins and porpoises) are a group of adapted marine mammals with an enigmatic history of transition from terrestrial to full aquatic habitat and rapid radiation in waters around the world. Throughout this evolution, the pathogen stress-response proteins must have faced challenges from the dramatic change of environmental pathogens in the completely different ecological niches cetaceans occupied. For this reason, cetaceans could be one of the most ideal candidate taxa for studying evolutionary process and associated driving mechanism of vertebrate innate immune systems such as Toll-like receptors (TLRs), which are located at the direct interface between the host and the microbial environment, act at the first line in recognizing specific conserved components of microorganisms, and translate them rapidly into a defense reaction.

Results
We used TLR4 as an example to test whether this traditionally regarded pattern recognition receptor molecule was driven by positive selection across cetacean evolutionary history. Overall, the lineage-specific selection test showed that the dN/dS (ω) values along most (30 out of 33) examined cetartiodactylan lineages were less than 1, suggesting a common effect of functional constraint. However, some specific codons made radical changes, fell adjacent to the residues interacting with lipopolysaccharides (LPS), and showed parallel evolution between independent lineages, suggesting that TLR4 was under positive selection. Especially, strong signatures of adaptive evolution on TLR4 were identified in two periods, one corresponding to the early evolutionary transition of the terrestrial ancestors of cetaceans from land to semi-aquatic (represented by the branch leading to whale + hippo) and from semi-aquatic to full aquatic (represented by the ancestral branch leading to cetaceans) habitat, and the other to the rapid diversification and radiation of oceanic dolphins.

Conclusions
This is the first study thus far to characterize the TLR gene in cetaceans. Our data present evidences that cetacean TLR4 has undergone adaptive evolution against the background of purifying selection in response to the secondary aquatic adaptation and rapid diversification in the sea. It is suggested that microbial pathogens in different environments are important factors that promote adaptive changes at cetacean TLR4 and new functions of some amino acid sites specialized for recognizing pathogens in dramatically contrasted environments to enhance the fitness for the adaptation and survival of cetaceans.
The complete genome sequence of the acarbose producer Actinoplanes sp. SE50/110
Authors: Schwientek Patrick , Szczepanowski Rafael , Rückert Christian , Kalinowski Jörn , Klein Andreas , Selber Klaus , Wehmeier Udo F , Stoye Jens , Pühler Alfred 
Published: March 2012

Abstract

Background

Actinoplanes sp. SE50/110 is known as the wild type producer of the alpha-glucosidase inhibitor acarbose, a potent drug used worldwide in the treatment of type-2 diabetes mellitus. As the incidence of diabetes is rapidly rising worldwide, an ever increasing demand for diabetes drugs, such as acarbose, needs to be anticipated. Consequently, derived Actinoplanes strains with increased acarbose yields are being used in large scale industrial batch fermentation since 1990 and were continuously optimized by conventional mutagenesis and screening experiments. This strategy reached its limits and is generally superseded by modern genetic engineering approaches. As a prerequisite for targeted genetic modifications, the complete genome sequence of the organism has to be known.

Results
Here, we present the complete genome sequence of Actinoplanes sp. SE50/110 [GenBank:CP003170], the first publicly available genome of the genus Actinoplanes, comprising various producers of pharmaceutically and economically important secondary metabolites. The genome features a high mean G + C content of 71.32% and consists of one circular chromosome with a size of 9,239,851 bp hosting 8,270 predicted protein coding sequences. Phylogenetic analysis of the core genome revealed a rather distant relation to other sequenced species of the family Micromonosporaceae whereas Actinoplanes utahensis was found to be the closest species based on 16S rRNA gene sequence comparison. Besides the already published acarbose biosynthetic gene cluster sequence, several new non-ribosomal peptide synthetase-, polyketide synthase- and hybrid-clusters were identified on the Actinoplanes genome. Another key feature of the genome represents the discovery of a functional actinomycete integrative and conjugative element.

Conclusions
The complete genome sequence of Actinoplanes sp. SE50/110 marks an important step towards the rational genetic optimization of the acarbose production. In this regard, the identified actinomycete integrative and conjugative element could play a central role by providing the basis for the development of a genetic transformation system for Actinoplanes sp. SE50/110 and other Actinoplanes spp. Furthermore, the identified non-ribosomal peptide synthetase- and polyketide synthase-clusters potentially encode new antibiotics and/or other bioactive compounds, which might be of pharmacologic interest.
Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD
Authors: Chen Yanwei , Huang Ping , Ai Wen , Li Xiaoli , Guo Wei , Zhang Jingnong , Yang Jiong 
Published: March 2012

Abstract

Background
Histone deacetylase (HDAC) is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD), while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail.

Methods
HDAC activities in peripheral blood mononuclear cells (PBMC) were investigated in patients with stable COPD (n = 26), non-smoking controls (n = 13), and smoking controls (n = 10), respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8) levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines.

Results
Compared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg), p < 0.001). In patients with COPD, HDAC activity was negatively correlated to smoke intensity (r = -0.867, p < 0.001). In COPD patients who had smoked for more than 40 pack-years, HDAC activity in PBMC was 40% lower than that in COPD patients who had smoked fewer than 40 pack-years.
Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities.

Conclusion
In patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.
Evaluation of CACC string stability using SUMO, Simulink, and OMNeT++
Authors: Lei Chenxi , van Eenennaam Emiel Martijn , Klein Wolterink Wouter , Ploeg Jeroen , Karagiannis Georgios , Heijenk Geert 
Published: March 2012

Abstract
Recent development in wireless technology enables communication between vehicles. The concept of co-operative adaptive cruise control (CACC)--which uses wireless communication between vehicles--aims at string stable behavior in a platoon of vehicles. "String stability" means any non-zero position, speed, and acceleration errors of an individual vehicle in a string do not amplify when they propagate upstream. In this article, we will discuss the string stability of CACC and evaluate its performance under varying packet loss ratios, beacon sending frequencies, and time headway settings in simulation experiments. The simulation framework is built up with a controller prototype, a traffic simulator, and a network simulator.
Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy
Authors: Dees Ellen , Miller Paul M. , Moynihan Katherine L. , Pooley Ryan D. , Hunt R. Pierre , Galindo Cristi L. , Rottman Jeffrey N. , Bader David M. 
Published: March 2012

Summary
CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs.
Zinc Transporter-8 Autoantibodies Improve Prediction of Type 1 Diabetes in Relatives Positive for the Standard Biochemical Autoantibodies
Authors: Yu Liping , Boulware David C. , Beam Craig A. , Hutton John C. , Wenzlau Janet M. , Greenbaum Carla J. , Bingley Polly J. , Krischer Jeffrey P. , Sosenko Jay M. , Skyler Jay S. , Eisenbarth George S. , Mahon Jeffrey L. ,   for the Type 1 Diabetes TrialNet Study Group
Published: March 2012

OBJECTIVE
We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A).

RESEARCH DESIGN AND METHODS
For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives.

RESULTS
ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA+ vs. 8 of 911 [0.8%] BAA−, P &lt; 0.001) and BAA number (177 of 1,683 [10.5%] single-, 221 of 384 [57.6%] double-, and 150 of 189 [79.4%] triple-BAA positivity, P &lt; 0.001). The 4-year diabetes risk was higher in single BAA+ relatives with ZnT8A than ZnT8A− relatives (31 vs. 7%, P &lt; 0.001). In multivariable analysis, age ≤20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively).

CONCLUSIONS
In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.