438 research outputs found
PARP inhibitors in metastatic prostate cancer
Poly-ADP ribose polymerase inhibitors (PARPi) are an emerging therapeutic option for the treatment of prostate cancer. Their primary mechanism of action is via induction of synthetic lethality in cells with underlying deficiencies in homologous recombination repair (HRR). In men with metastatic castrate-resistant prostate cancer (mCRPC) and select HRR pathway alterations, PARPi treatment has been shown to induce objective tumor responses as well as improve progression free and overall survival. Presently, there are two PARPi, olaparib and rucaparib, that are FDA approved in the treatment of mCRPC. Ongoing research is focused on identifying which HRR alterations are best suited to predict response to PARPi so that these therapies can be most effectively utilized in the clinic. While resistance to PARPi remains a concern, combination therapies may represent a mechanism to overcome or delay resistance
Association Between Community Social Vulnerability and Preventable Hospitalizations
Preventable hospitalizations are common and costly events that burden patients and our health care system. While research suggests that these events are strongly linked to ambulatory care access, emerging evidence suggests they may also be sensitive to a patient’s social, environmental, and economic conditions. This study examines the association between variations in social vulnerability and preventable hospitalization rates. We conducted a cross-sectional analysis of county-level preventable hospitalization rates for 33 states linked with data from the 2020 Social Vulnerability Index (SVI). Preventable hospitalizations were 40% higher in the most vulnerable counties compared with the least vulnerable. Adjusted regression results confirm the strong relationship between social vulnerability and preventable hospitalizations. Our results suggest wide variation in community-level preventable hospitalization rates, with robust evidence that variation is strongly related to a community’s social vulnerability. The human toll, societal cost, and preventability of these hospitalizations make understanding and mitigating these inequities a national priority
Rice Galaxy: An open resource for plant science
Background: Rice molecular genetics, breeding, genetic diversity, and allied research (such as rice-pathogen interaction) have adopted sequencing technologies and high-density genotyping platforms for genome variation analysis and gene discovery. Germplasm collections representing rice diversity, improved varieties, and elite breeding materials are accessible through rice gene banks for use in research and breeding, with many having genome sequences and high-density genotype data available. Combining phenotypic and genotypic information on these accessions enables genome-wide association analysis, which is driving quantitative trait loci discovery and molecular marker development. Comparative sequence analyses across quantitative trait loci regions facilitate the discovery of novel alleles. Analyses involving DNA sequences and large genotyping matrices for thousands of samples, however, pose a challenge to non−computer savvy rice researchers. Findings: The Rice Galaxy resource has shared datasets that include high-density genotypes from the 3,000 Rice Genomes project and sequences with corresponding annotations from 9 published rice genomes. The Rice Galaxy web server and deployment installer includes tools for designing single-nucleotide polymorphism assays, analyzing genome-wide association studies, population diversity, rice−bacterial pathogen diagnostics, and a suite of published genomic prediction methods. A prototype Rice Galaxy compliant to Open Access, Open Data, and Findable, Accessible, Interoperable, and Reproducible principles is also presented. Conclusions: Rice Galaxy is a freely available resource that empowers the plant research community to perform state-of-the-art analyses and utilize publicly available big datasets for both fundamental and applied science
Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?
Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC
GREAT3 results I: systematic errors in shear estimation and the impact of real galaxy morphology
We present first results from the third GRavitational lEnsing Accuracy
Testing (GREAT3) challenge, the third in a sequence of challenges for testing
methods of inferring weak gravitational lensing shear distortions from
simulated galaxy images. GREAT3 was divided into experiments to test three
specific questions, and included simulated space- and ground-based data with
constant or cosmologically-varying shear fields. The simplest (control)
experiment included parametric galaxies with a realistic distribution of
signal-to-noise, size, and ellipticity, and a complex point spread function
(PSF). The other experiments tested the additional impact of realistic galaxy
morphology, multiple exposure imaging, and the uncertainty about a
spatially-varying PSF; the last two questions will be explored in Paper II. The
24 participating teams competed to estimate lensing shears to within systematic
error tolerances for upcoming Stage-IV dark energy surveys, making 1525
submissions overall. GREAT3 saw considerable variety and innovation in the
types of methods applied. Several teams now meet or exceed the targets in many
of the tests conducted (to within the statistical errors). We conclude that the
presence of realistic galaxy morphology in simulations changes shear
calibration biases by per cent for a wide range of methods. Other
effects such as truncation biases due to finite galaxy postage stamps, and the
impact of galaxy type as measured by the S\'{e}rsic index, are quantified for
the first time. Our results generalize previous studies regarding sensitivities
to galaxy size and signal-to-noise, and to PSF properties such as seeing and
defocus. Almost all methods' results support the simple model in which additive
shear biases depend linearly on PSF ellipticity.Comment: 32 pages + 15 pages of technical appendices; 28 figures; submitted to
MNRAS; latest version has minor updates in presentation of 4 figures, no
changes in content or conclusion
PTF1 J071912.13+485834.0: An outbursting AM CVn system discovered by a synoptic survey
We present extensive photometric and spectroscopic observations of PTF1
J071912.13+485834.0, an outbursting AM CVn system discovered by the Palomar
Transient Factory (PTF). AM CVn systems are stellar binaries with some of the
smallest separations known and orbital periods ranging from 5 to 65 minutes.
They are believed to be composed of a white dwarf accretor and a
(semi)-degenerate He-rich donor and are considered to be the helium equivalents
of Cataclysmic Variables. We have spectroscopically and photometrically
identified an orbital period of 26.77 \pm 0.02 minutes for PTF1
J071912.13+485834.0 and found a super-outburst recurrence time of greater than
65 days along with the presence of "normal" outbursts - rarely seen in AM CVn
systems but well known in super-outbursting Cataclysmic Variables. We present a
long-term light curve over two super-cycles as well as high cadence photometry
of both outburst and quiescent stages, both of which show clear variability. We
also compare both the outburst and quiescent spectra of PTF1
J071912.13+485834.0 to other known AM CVn systems, and use the quiescent
phase-resolved spectroscopy to determine the origin of the photometric
variability. Finally, we draw parallels between the different subclasses of SU
UMa-type Cataclysmic Variables and outbursting AM CVn systems. We conclude by
predicting that the Palomar Transient Factory may more than double the number
of outbursting AM CVn systems known, which would greatly increase our
understanding of AM CVn systems.Comment: 11 pages, 10 figures; accepted to Ap
First Data Release of the Hyper Suprime-Cam Subaru Strategic Program
The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered
imaging survey aimed at addressing some of the most outstanding questions in
astronomy today, including the nature of dark matter and dark energy. The
survey has been awarded 300 nights of observing time at the Subaru Telescope
and it started in March 2014. This paper presents the first public data release
of HSC-SSP. This release includes data taken in the first 1.7 years of
observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers
covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and
~27.0 mag, respectively (5sigma for point sources). All the layers are observed
in five broad bands (grizy), and the Deep and UltraDeep layers are observed in
narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in
the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF
photometry (rms) both internally and externally (against Pan-STARRS1), and ~10
mas and 40 mas internal and external astrometric accuracy, respectively. Both
the calibrated images and catalogs are made available to the community through
dedicated user interfaces and database servers. In addition to the pipeline
products, we also provide value-added products such as photometric redshifts
and a collection of public spectroscopic redshifts. Detailed descriptions of
all the data can be found online. The data release website is
https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for
publication in PAS
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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