bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating palliative care with intensive care for critically ill patients with lung cancer
Authors: Gay Elizabeth B , Weiss Stefanie P , Nelson Judith E 
Published: February 2012

Abstract
With newer information indicating more favorable outcomes of intensive care therapy for lung cancer patients, intensivists increasingly are willing to initiate an aggressive trial of this therapy. Concerns remain, however, that the experience of the intensive care unit for patients with lung cancer and their families often may be distressing. Regardless of prognosis, all patients with critical illness should receive high-quality palliative care, including symptom control, communication about appropriate care goals, and support for both patient and family throughout the illness trajectory. In this article, we suggest strategies for integrating palliative care with intensive care for critically ill lung cancer patients. We address assessment and management of symptoms, knowledge and skill needed for effective communication, and interdisciplinary collaboration for patient and family support. We review the role of expert consultants in providing palliative care in the intensive care unit, while highlighting the responsibility of all critical care clinicians to address basic palliative care needs of patients and their families.
Premenopausal serum androgens and breast cancer risk: a nested case-control study
Authors: Zeleniuch-Jacquotte Anne , Afanasyeva Yelena , Kaaks Rudolf , Rinaldi Sabina , Scarmo Stephanie , Liu Mengling , Arslan Alan A , Toniolo Paolo , Shore Roy E , Koenig Karen L 
Published: February 2012

Abstract
Introduction
Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.

Methods
A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.

Results
Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls).

Conclusions
Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.
Static and dynamic effective stress coefficient of chalk
Authors: Alam M. Monzurul , Fabricius Ida Lykke , Christensen Helle Foged 
Published: February 2012

Deformation of a hydrocarbon reservoir can ideally be used to estimate the effective stress acting on it. The effective stress in the subsurface is the difference between the stress due to the weight of the sediment and a fraction (effective stress coefficient) of the pore pressure. The effective stress coefficient is thus relevant for studying reservoir deformation and for evaluating 4D seismic for the correct pore pressure prediction. The static effective stress coefficient [Formula: see text] is estimated from mechanical tests and is highly relevant for effective stress prediction because it is directly related to mechanical strain in the elastic stress regime. The corresponding dynamic effective stress coefficient [Formula: see text] is easy to estimate from density and velocity of acoustic (elastic) waves. We studied [Formula: see text] and [Formula: see text] of chalk from the reservoir zone of the Valhall field, North Sea, and found that [Formula: see text] and [Formula: see text] vary with differential stress (overburden stress-pore pressure). For Valhall reservoir chalk with 40% porosity, [Formula: see text] ranges between 0.98 and 0.85 and decreases by 10% if the differential stress is increased by 25 MPa. In contrast, for chalk with 15% porosity from the same reservoir, [Formula: see text] ranges between 0.85 and 0.70 and decreases by 5% due to a similar increase in differential stress. Our data indicate that [Formula: see text] measured from sonic velocity data falls in the same range as for [Formula: see text], and that [Formula: see text] is always below unity. Stress-dependent behavior of [Formula: see text] is similar (decrease with increasing differential stress) to that of [Formula: see text] during elastic deformation caused by pore pressure buildup, for example, during waterflooding. By contrast, during the increase in differential stress, as in the case of pore pressure depletion due to production, [Formula: see text] increases with stress while [Formula: see text] decreases.
Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer
Authors: Yee Nelson S. , Zhou Weiqiang , Chun Stephen G. , Liang I-Chau , Yee Rosemary K. 
Published: February 2012

Summary
Histone deacetylases (HDACs) and RNA polymerase III (POLR3) play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.
Histological and MS spectrometric analyses of the modified tissue of bulgy form tadpoles induced by salamander predation
Authors: Mori Tsukasa , Kitani Yoichiro , Ogihara Jun , Sugiyama Manabu , Yamamoto Goshi , Kishida Osamu , Nishimura Kinya 
Published: February 2012

SummaryThe rapid induction of a defensive morphology by a prey species in face of a predation risk is an intriguing in ecological context; however, the physiological mechanisms that underlie this phenotypic plasticity remain uncertain. Here we investigated the phenotypic changes shown by Rana pirica tadpoles in response to a predation threat by larvae of the salamander Hynobius retardatus. One such response is the bulgy morph phenotype, a relatively rapid swelling in size by the tadpoles that begins within 4 days and reaches a maximum at 8 to 10 days. We found that although the total volume of bodily fluid increased significantly (P&lt;0.01) in bulgy morph tadpoles, osmotic pressure was maintained at the same level as control tadpoles by a significant increase (P&lt;0.01) in Na and Cl ion concentrations. In our previous report, we identified a novel frog gene named pirica that affects the waterproofing of the skin membrane in tadpoles. Our results support the hypothesis that predator-induced expression of pirica on the skin membrane causes retention of absorbed water. Midline sections of bulgy morph tadpoles showed the presence of swollen connective tissue beneath the skin that was sparsely composed of cells containing hyaluronic acid. Mass spectrographic (LC-MS/MS) analysis identified histone H3 and 14-3-3 zeta as the most abundant constituents in the liquid aspirated from the connective tissue of bulgy tadpoles. Immunohistochemistry using antibodies against these proteins showed the presence of non-chromatin associated histone H3 in the swollen connective tissue. Histones and 14-3-3 proteins are also involved in antimicrobial activity and secretion of antibacterial proteins, respectively. Bulgy tadpoles have a larger surface area than controls, and their skin often has bite wounds inflicted by the larval salamanders. Thus, formation of the bulgy morph may also require and be supported by activation of innate immune systems.
Microtube Device for Selectin-Mediated Capture of Viable Circulating Tumor Cells from Blood
Authors: Hughes Andrew D , Mattison Jeff , Western Laura T , Powderly John D , Greene Bryan T , King Michael R 
Published: February 2012

Abstract

BACKGROUND
Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage.

METHODS
We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer.

RESULTS
Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20–704 viable CTCs per 3.75-mL sample, achieving purities of 18%–80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading.

CONCLUSIONS
The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities &gt;50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.
Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype
Authors: Heffelfinger Christopher , Ouyang Zhengqing , Engberg Anna , Leffell David J , Hanlon Allison M , Gordon Patricia B , Zheng Wei , Zhao Hongyu , Snyder Michael P , Bale Allen E 
Published: February 2012

AbstractBasal cell carcinomas (BCCs) are the most common cancers in the United States. The histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study, global miRNA expression was quantified by high-throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. Quantitative polymerase chain reaction assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.
Evolution of a Large, Conserved, and Syntenic Gene Family in Insects
Authors: Shah Neethu , Dorer Douglas R , Moriyama Etsuko N , Christensen Alan C 
Published: February 2012

AbstractThe Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. Osiris gene homologs have also been found in the expressed sequence tag sequences of various other insects but are absent from all groups that are not insects, including crustacea and arachnids. It is clear that the gene family evolved by gene duplication and neofunctionalization very soon after the divergence of the insects from other arthropods but before the divergence of the insects from one another and that the sequences and synteny have been maintained by selection ever since.
Narrowing Down the Mapping of Plant Sex-Determination Regions Using New Y-Chromosome-Specific Markers and Heavy-Ion Beam Irradiation-Induced Y-Deletion Mutants inSilene latifolia
Authors: Fujita Naoko , Torii Chihiro , Ishii Kotaro , Aonuma Wataru , Shimizu Yuji , Kazama Yusuke , Abe Tomoko , Kawano Shigeyuki 
Published: February 2012

AbstractSilene latifolia is a well-studied model system for plant XY sex determination. Three maleness factors are thought to function on the Y chromosome, gynoecium suppression factor (GSF), stamen-promoting factor (SPF), and male fertility factor (MFF), and their deletions result in hermaphrodites, anther defects, and pollen defects, respectively. Although a framework map of the Y chromosome exists, the sex determination genes have not been identified, and no markers close enough to potentially be used for BAC library screening are yet available. The analysis of Y deletion mutants by Y-chromosome-specific STS markers is an efficient way to isolate sex determination regions, but more Y-specific STS markers are needed to accelerate the exploration of sex determination factors. Herein, we report a marker design method that uses simple sequence repeats, which is especially effective on the Y chromosome of S. latifolia because it contains many simple sequence repeats. Six new Y-chromosome-specific STS markers were obtained, SmicSy1–6. These were used to detect relatively small Y deletion sites in heavy-ion beam irradiation-induced mutants. The mapping of male sex determination regions was narrowed down by using more markers and smaller-sized Y deletion mutants. One new marker, SmicSy6, is a proximal marker to SPF and, thus, a second index for SPF. The region including SPF is thought to be located between two SPF proximal markers. The flower phenotype correlates with the deletion size of SPF using SPF proximal markers. These findings represent new progress in isolating the sex determination factor, which has been studied for more than 50 years.
Whole-Genome Sequencing ofSordaria macrosporaMutants Identifies Developmental Genes
Authors: Nowrousian Minou , Teichert Ines , Masloff Sandra , Kück Ulrich 
Published: February 2012

AbstractThe study of mutants to elucidate gene functions has a long and successful history; however, to discover causative mutations in mutants that were generated by random mutagenesis often takes years of laboratory work and requires previously generated genetic and/or physical markers, or resources like DNA libraries for complementation. Here, we present an alternative method to identify defective genes in developmental mutants of the filamentous fungus Sordaria macrospora through Illumina/Solexa whole-genome sequencing. We sequenced pooled DNA from progeny of crosses of three mutants and the wild type and were able to pinpoint the causative mutations in the mutant strains through bioinformatics analysis. One mutant is a spore color mutant, and the mutated gene encodes a melanin biosynthesis enzyme. The causative mutation is a G to A change in the first base of an intron, leading to a splice defect. The second mutant carries an allelic mutation in the pro41 gene encoding a protein essential for sexual development. In the mutant, we detected a complex pattern of deletion/rearrangements at the pro41 locus. In the third mutant, a point mutation in the stop codon of a transcription factor-encoding gene leads to the production of immature fruiting bodies. For all mutants, transformation with a wild type-copy of the affected gene restored the wild-type phenotype. Our data demonstrate that whole-genome sequencing of mutant strains is a rapid method to identify developmental genes in an organism that can be genetically crossed and where a reference genome sequence is available, even without prior mapping information.
Extent With Modification: Leg Patterning in the BeetleTribolium castaneumand the Evolution of Serial Homologs
Authors: Angelini David R , Smith Frank W , Jockusch Elizabeth L 
Published: February 2012

AbstractSerial homologs are similar structures that develop at different positions within a body plan. These structures share some, but not all, aspects of developmental patterning, and their evolution is thought to be constrained by shared, pleiotropic gene functions. Here we describe the functions of 17 developmental genes during metamorphic development of the legs in the red flour beetle, Tribolium castaneum. This study provides informative comparisons between appendage development in Drosophila melanogaster and T. castaneum, between embryonic and adult development in T. castaneum, and between the development of serially homologous appendages. The leg gap genes Distal-less and dachshund are conserved in function. Notch signaling, the zinc-finger transcription factors related to odd-skipped, and bric-à-brac have conserved functions in promoting joint development. homothorax knockdown alters the identity of proximal leg segments but does not reduce growth. Lim1 is required for intermediate leg development but not distal tarsus and pretarsus development as in D. melanogaster. Development of the tarsus requires decapentaplegic, rotund, spineless, abrupt, and bric-à-brac and the EGF ligand encoded by Keren. Metathoracic legs of T. castaneum have four tarsomeres, whereas other legs have five. Patterns of gene activity in the tarsus suggest that patterning in the middle of the tarsal region, not the proximal- or distal-most areas, is responsible for this difference in segment number. Through comparisons with other recent studies of T. castaneum appendage development, we test hypotheses for the modularity or interdependence of development during evolution of serial homologs.
Genome-Wide Association Mapping of Quantitative Traits in Outbred Mice
Authors: Zhang Weidong , Korstanje Ron , Thaisz Jill , Staedtler Frank , Harttman Nicole , Xu Lingfei , Feng Minjie , Yanas Liane , Yang Hyuna , Valdar William , Churchill Gary A , DiPetrillo Keith 
Published: February 2012

Abstract
Recent developments in high-density genotyping and statistical analysis methods that have enabled genome-wide association studies in humans can also be applied to outbred mouse populations. Increased recombination in outbred populations is expected to provide greater mapping resolution than traditional inbred line crosses, improving prospects for identifying the causal genes. We carried out genome-wide association mapping by using 288 mice from a commercially available outbred stock; NMRI mice were genotyped with a high-density single-nucleotide polymorphism array to map loci influencing high-density lipoprotein cholesterol, systolic blood pressure, triglyceride levels, glucose, and urinary albumin-to-creatinine ratios. We found significant associations (P &lt; 10−5) with high-density lipoprotein cholesterol and identified Apoa2 and Scarb1, both of which have been previously reported, as candidate genes for these associations. Additional suggestive associations (P &lt; 10−3) identified in this study were also concordant with published quantitative trait loci, suggesting that we are sampling from a limited pool of genetic diversity that has already been well characterized. These findings dampen our enthusiasm for currently available commercial outbred stocks as genetic mapping resources and highlight the need for new outbred populations with greater genetic diversity. Despite the lack of novel associations in the NMRI population, our analysis strategy illustrates the utility of methods that could be applied to genome-wide association studies in humans.