bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines
Authors: Cavazzoni Andrea , Alfieri Roberta R , Cretella Daniele , Saccani Francesca , Ampollini Luca , Galetti Maricla , Quaini Federico , Graiani Gallia , Madeddu Denise , Mozzoni Paola , Galvani Elena , La Monica Silvia , Bonelli Mara , Fumarola Claudia , Mutti Antonio , Carbognani Paolo , Tiseo Marcello , Barocelli Elisabetta , Petronini Pier Giorgio , Ardizzoni Andrea 
Published: December 2012

Abstract

Background
The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.

Results
In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone.

Conclusion
Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.
Ethanolamine utilization in Vibrio alginolyticus
Authors: Khatri Neelam , Khatri Indu , Subramanian Srikrishna , Raychaudhuri Saumya 
Published: December 2012

Abstract
Ethanolamine is used as an energy source by phylogenetically diverse bacteria including pathogens, by the concerted action of proteins from the eut-operon. Previous studies have revealed the presence of eutBC genes encoding ethanolamine-ammonia lyase, a key enzyme that breaks ethanolamine into acetaldehyde and ammonia, in about 100 bacterial genomes including members of gamma-proteobacteria. However, ethanolamine utilization has not been reported for any member of the Vibrio genus. Our comparative genomics study reveals the presence of genes that are involved in ethanolamine utilization in several Vibrio species. Using Vibrio alginolyticus as a model system we demonstrate that ethanolamine is better utilized as a nitrogen source than as a carbon source.

Reviewers

This article was reviewed by Dr. Lakshminarayan Iyer and Dr. Vivek Anantharaman (nominated by Dr. L Aravind).
Data reduction for cough studies using distribution of audio frequency content
Authors: Barton Antony , Gaydecki Patrick , Holt Kimberley , Smith Jaclyn A 
Published: December 2012

Abstract

Background
Recent studies suggest that objectively quantifying coughing in audio recordings offers a novel means to understand coughing and assess treatments. Currently, manual cough counting is the most accurate method for quantifying coughing. However, the demand of manually counting cough records is substantial, demonstrating a need to reduce record lengths prior to counting whilst preserving the coughs within them. This study tested the performance of an algorithm developed for this purpose.

Methods
20 subjects were recruited (5 healthy smokers and non-smokers, 5 chronic cough, 5 chronic obstructive pulmonary disease and 5 asthma), fitted with an ambulatory recording system and recorded for 24 hours. The recordings produced were divided into 15 min segments and counted. Periods of inactive audio in each segment were removed using the median frequency and power of the audio signal and the resulting files re-counted.

Results
The median resultant segment length was 13.9 s (IQR 56.4 s) and median 24 hr recording length 62.4 min (IQR 100.4). A median of 0.0 coughs/h (IQR 0.0-0.2) were erroneously removed and the variability in the resultant cough counts was comparable to that between manual cough counts. The largest error was seen in asthmatic patients, but still only 1.0% coughs/h were missed.

Conclusions
These data show that a system which measures signal activity using the median audio frequency can substantially reduce record lengths without significantly compromising the coughs contained within them.
Palindromic sequence impedes sequencing-by-ligation mechanism
Authors: Huang Yu-Feng , Chen Sheng-Chung , Chiang Yih-Shien , Chen Tzu-Han , Chiu Kuo-Ping 
Published: December 2012

Abstract

Background
Current next-generation sequencing (NGS) platforms adopt two types of sequencing mechanisms: by synthesis or by ligation. The former is employed by 454 and Solexa systems, while the latter by SOLiD system. Although the pros and cons for each sequencing mechanism have more or less been discussed in a number of occasions, the potential obstacle imposed by palindromic sequences has not yet been addressed.

Methods
To test the effect of the palindromic region on sequencing efficacy, we clonally amplified a paired-end ditag sequence composed of a 24-bp palindromic sequence flanked by a pair of tags from the E. coli genome. We used the near homogeneous fragments produced from Mme I digestion of the amplified clone to generate a sequencing library for SOLiD 5500xl sequencer.

Results
Results showed that, traditional ABI sequencers, which adopt sequencing-by-synthesis mechanism, were able to read through the palindromic region. However, SOLiD 5500xl was unable to do so. Instead, the palindromic region was read as miscellaneous random sequences. Moreover, readable tag sequence turned obscure ~2 bp prior to the palindromic region.

Conclusions
Taken together, we demonstrate that SOLiD machines, which employ sequencing-by-ligation mechanism, are unable to read through the palindromic region. On the other hand, sequencing-by-synthesis sequencers had no difficulty in doing so.
Hematometra presenting as an acute abdomen in a 13-year-old postmenarchal girl: a case report
Authors: Klimek Peter , Klimek Miriam , Kessler Ulf , Oesch Valerie , Wolf Rainer , Stranzinger Enno , Mueller Michael D , Zachariou Zacharias 
Published: December 2012

Abstract

Introduction
Most underlying diseases for abdominal pain in children are not dangerous. However some require rapid diagnosis and treatment, such as acute ovarian torsion or appendicitis. Since reaching a diagnosis can be difficult, and delayed treatment of potentially dangerous diseases might have significant consequences, exploratory laparoscopy is a diagnostic and therapeutic option for patients who have unclear and potentially hazardous abdominal diseases. Here we describe a case where the anomaly could not be identified using a laparoscopy in an adolescent girl with acute abdomen.

Case presentation
A 13-year old postmenarchal caucasian female presented with an acute abdomen. Emergency sonography could not exclude ovarian torsion. Accurate diagnosis and treatment were achieved only after an initial laparoscopy followed by a laparotomy and after a magnetic resonance imaging scan a further laparotomy. The underlying disease was hematometra of the right uterine horn in a uterus didelphys in conjunction with an imperforate right cervix.

Conclusion
This report demonstrates that the usual approach for patients with acute abdominal pain may not be sufficient in emergency situations.
Multivariate methods and software for association mapping in dose‐response genome‐wide association studies
Authors: Brown Chad C , Havener Tammy M , Medina Marisa Wong , Krauss Ronald M , McLeod Howard L , Motsinger‐Reif Alison A 
Published: December 2012

Abstract

Background
The large sample sizes, freedom of ethical restrictions and ease of repeated measurements make cytotoxicity assays of immortalized lymphoblastoid cell lines a powerful new in vitro method in pharmacogenomics research. However, previous studies may have over‐simplified the complex differences in dose‐response profiles between genotypes, resulting in a loss of power.

Methods
The current study investigates four previously studied methods, plus one new method based on a multivariate analysis of variance (MANOVA) design. A simulation study was performed using differences in cancer drug response between genotypes for biologically meaningful loci. These loci also showed significance in separate genome‐wide association studies. This manuscript builds upon a previous study, where differences in dose‐response curves between genotypes were constructed using the hill slope equation.

Conclusion
Overall, MANOVA was found to be the most powerful method for detecting real signals, and was also the most robust method for detection using alternatives generated with the previous simulation study. This method is also attractive because test statistics follow their expected distributions under the null hypothesis for both simulated and real data. The success of this method inspired the creation of the software program MAGWAS. MAGWAS is a computationally efficient, user‐friendly, open source software tool that works on most platforms and performs GWASs for individuals having multivariate responses using standard file formats.
Partial purification and properties of cyclodextrin glycosiltransferase (CGTase) from alkalophilic Bacillus species
Authors: Mora Marlene M Martínez , Sánchez Karel Hernández , Santana Reynaldo Villalonga , Rojas Arley Pérez , Ramírez Héctor L , Torres-Labandeira Juan José 
Published: December 2012

Abstract
Cyclodextrin glucanotransferase (CGTase, EC 2.4.1.9) is an unique enzyme capable of converting starch and related substrates into cyclodextrins (CDs). In this paper, we report an one step gel purification method of CGTase from Bacillus sp. and later enzyme characterization. The Bacillus sp. strain was isolated from a Colocacia esculenta rizospheric soil sample and the CGTase production was carried out in alkaline medium (pH=10). The CGTase purification from the culture supernatant was performed by gel filtration. The enzyme was purified in one step with a recovery of 87.3% activity and 40-fold purification for specific enzymatic activity of 2.24 U/mg. Optimal activity was observed at pH 5.0 in citrate-phosphate buffer, and the enzyme retained almost 100 % of its activity between pH 5.5 and 10 after incubation for 1 h at 4°C. The enzyme exhibited maximum activity at 55°C and showed a T50% of 70°C. The ratio of α:β:γ CD formed by the enzyme was 0.74:1:0.61 for soluble starch and 0.29:1:0.85 for cocoyam starch.
The association between depression, socio-economic factors and dietary intake in mothers having primary school children living in Rey, south of Tehran, Iran
Authors: Payab Moloud , Motlagh Ahmad-reza Dorosty , Eshraghian Mohammadreza , Rostami Reza , Siassi Fereydoun , abbasi Behnood , Ahmadi Mehrnaz , Karimi Tina , Mahjouri Mohammad Yoosef , Seifirad Soroush 
Published: December 2012

Abstract
Background
According to the WHO report released in 2000, about 121 million people worldwide suffer from depression. The present study aimed to explore factors influencing depression in mothers from Rey, South of Tehran, Iran; who had elementary school children.

Methods
The cross-sectional survey was conducted in spring 2010. Four hundred thirty mothers who had elementary school children, were selected through a two stage cluster sampling. Beck Depression Inventory (BDI) was used to assess depression in the mothers and a 24-hour food recall was used to collect information regarding their dietary intake. General information regarding economic condition and socio-economic status were also gathered using a questionnaire. The data was analyzed using chi-square, one-way analysis of variance and simple regression tests.

Results
In our study, 51.4% of the mothers suffered from depression. There was an inverse correlation between the educational level of the mothers and the heads of household, their occupational status, their marital status, their socio-economic condition and depression. Conversely, any increase in the family size worsened the depression. The daily intake of different macronutrients, except for fat, was lower in individuals of depressed group.

Conclusion
The present study emphasized the fact that more attention should be paid to the educational level and economic condition of the family in order to reduce maternal depression. Family size also plays an important role in this regard.
Neutrophil and endothelial adhesive function during human fetal ontogeny
Authors: Nussbaum Claudia , Gloning Anna , Pruenster Monika , Frommhold David , Bierschenk Susanne , Genzel-Boroviczény Orsolya , von Andrian Ulrich H , Quackenbush Elizabeth , Sperandio Markus 
Published: December 2012

Abstract
Leukocyte recruitment is ontogenetically regulated during fetal life, with strongly impaired adhesiveness of fetal leukocytes and endothelial cells, during early fetal development.
Attenuation of the immune response contributes to the high rate of neonatal infections, particularly in premature infants. Whereas our knowledge of innate immune functions in mature neonates is growing, little is known about the ontogeny of neutrophil recruitment. We investigated neutrophils and ECs in the course of gestation with respect to rolling and adhesive functions. With the use of microflow chambers, we demonstrate that the neutrophilˈs ability to roll and adhere directly correlates with gestational age. These adhesion-related abilities are very rare in extremely premature infants (&lt;30 weeks of gestation), which may correlate with our observation of markedly reduced expression of PSGL-1 and Mac-1 on neutrophils in preterm infants. In parallel, the capacity of HUVECs to mediate neutrophil adhesion under flow increases with gestational age. In addition, HUVECs from extremely premature infants exerting the lowest ability to recruit adult neutrophils show a diminished up-regulation of E-selectin and ICAM-1. Finally, by following neutrophil function postnatally, we show that maturation of PMN recruitment proceeds equivalently during extra- and intrauterine development. Thus, PMN recruitment and EC adhesion-related functions are ontogenetically regulated in the fetus, which might contribute significantly to the high risk of life-threatening infections in premature infants.
Anisotropic parsimonious prestack depth migration
Authors: Oropeza Ernesto V. , McMechan George A. 
Published: December 2012

An efficient Kirchhoff-style prestack depth migration, called “parsimonious” migration, was developed a decade ago for isotropic 2D and 3D media by using measured slownesses to reduce the amount of ray tracing by orders of magnitude. It is conceptually similar to “map” migration, but its implementation has some differences. We have extended this approach to 2D tilted transversely isotropic (TTI) media and illustrated it with synthetic P-wave data. Although the framework of isotropic parsimonious may be retained, the extension to TTI media requires redevelopment of each of the numerical components, calculation of the phase and group velocity for TTI media, development of a new two-point anisotropic ray tracer, and substitution of an initial-angle isotropic shooting ray-trace algorithm for an anisotropic one. The model parameterization consists of Thomsen’s parameters ([Formula: see text], [Formula: see text], [Formula: see text]) and the tilt angle of the symmetry axis of the TI medium. The parsimonious anisotropic migration algorithm is successfully applied to synthetic data from a TTI version of the Marmousi2 model. The quality of the image improves by weighting the impulse response by the calculation of the anisotropic Fresnel radius. The accuracy and speed of this migration makes it useful for anisotropic velocity model building. The elapsed computing time for 101 shots for the Marmousi2 TTI model is 35 s per shot (each with 501 traces) in 32 Opteron cores.
Integrated application of heliborne and ground electromagnetic surveys for mapping EM conductor for uranium exploration and its subsurface validation, North Delhi Fold Belt, Rajasthan, India: A case study
Authors: Chaturvedi A. K. , Lotter Cas , Tripathi Shailesh , Maurya A. K. , Patra Indrajit , Parihar P. S. 
Published: December 2012

A fracture-controlled uranium deposit was identified in Proterozoic Ajabgarh metasediments of the North Delhi Fold Belt within the Khetri subbasin at Rohil, Sikar district, Rajasthan, India. Uranium mineralization in the area is associated with geologic structures, albitization, and pyroxenization of metasediments and conductors such as metallic sulfides and carbonaceous phyllites/graphitic schists. To locate uranium mineralization akin to Rohil in nearby thick soil covered areas, this association was targeted through heliborne geophysical surveys. High-resolution heliborne magnetic and time domain electromagnetic (TEM) surveys were conducted around Rohil. The survey delineated several targets with favorable geologic structures and conductors such as graphitic schist for further uranium exploration. One favorable target near Chappar village was taken up for follow-up exploration work. The EM conductor mapped from heliborne survey was subsequently validated through ground time-domain electromagnetic surveys and subsurface exploration. Modeling of heliborne and ground-based electromagnetic data revealed the presence of subsurface conducting bodies with comparable model parameters. Drilling established the presence of a subsurface conductor up to a depth of 300 m, which was attributed to the presence of graphite and sulfides (pyrrhotite) along foliation plane of carbon phyllite/graphitic schist/quartz-biotite schist and calc-silicate rock. Further detailed laboratory investigations (petrology/X-ray diffraction) of selected core samples from the conductive zones confirmed the presence of pyrrhotite and graphite responsible for EM signature. This study, carried out by using multiparameter data sets, proved the efficacy of heliborne surveys in locating favorable targets for uranium exploration in Ajabgarh group of rocks.
Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer
Authors: Wolff Antonio C. , Lazar Ann A. , Bondarenko Igor , Garin August M. , Brincat Stephen , Chow Louis , Sun Yan , Neskovic-Konstantinovic Zora , Guimaraes Rodrigo C. , Fumoleau Pierre , Chan Arlene , Hachemi Soulef , Strahs Andrew , Cincotta Maria , Berkenblit Anna , Krygowski Mizue , Kang Lih Lisa , Moore Laurence , Hayes Daniel F. 
Published: December 2012

Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation.
Prevalence and Type ofBRCAMutations in Hispanics Undergoing Genetic Cancer Risk Assessment in the Southwestern United States: A Report From the Clinical Cancer Genetics Community Research Network
Authors: Weitzel Jeffrey N. , Clague Jessica , Martir-Negron Arelis , Ogaz Raquel , Herzog Josef , Ricker Charité , Jungbluth Chelsy , Cina Cheryl , Duncan Paul , Unzeitig Gary , Saldivar J. Salvador , Beattie Mary , Feldman Nancy , Sand Sharon , Port Danielle , Barragan Deborah I. , John Esther M. , Neuhausen Susan L. , Larson Garrett P. 
Published: December 2012

PurposeTo determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA).Patients and MethodsHispanics (n = 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board–approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n = 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement.ResultsDeleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States.ConclusionBRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.