bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat mixed-phenotype acute leukemia
Authors: Wolach Ofir , Stone Richard M. 
Published: January 2015

Abstract
Mixed-phenotype acute leukemia (MPAL) encompasses a heterogeneous group of rare leukemias in which assigning a single lineage of origin is not possible. A variety of different terms and classification systems have been used historically to describe this entity. MPAL is currently defined by a limited set of lineage-specific markers proposed in the 2008 World Health Organization monograph on classification of tumors of hematopoietic and lymphoid tissues. In adult patients, MPAL is characterized by relative therapeutic resistance that may be attributed in part to the high proportion of patients with adverse cytogenetic abnormalities. No prospective, controlled trials exist to guide therapy. The limited available data suggest that an “acute lymphoblastic leukemia–like” regimen followed by allogeneic stem-cell transplant may be advisable; addition of a tyrosine kinase inhibitor in patients with t(9;22) translocation is recommended. The role of immunophenotypic and genetic markers in guiding chemotherapy choice and postremission strategy, as well as the utility of targeted therapies in non–Ph-positive MPALs is unknown.
Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data
Authors: Fernandez-Cuesta Lynnette , Sun Ruping , Menon Roopika , George Julie , Lorenz Susanne , Meza-Zepeda Leonardo A , Peifer Martin , Plenker Dennis , Heuckmann Johannes M , Leenders Frauke , Zander Thomas , Dahmen Ilona , Koker Mirjam , Schöttle Jakob , Ullrich Roland T , Altmüller Janine , Becker Christian , Nürnberg Peter , Seidel Henrik , Böhm Diana , Göke Friederike , Ansén Sascha , Russell Prudence A , Wright Gavin M , Wainer Zoe , Solomon Benjamin , Petersen Iver , Clement Joachim H , Sänger Jörg , Brustugun Odd-Terje , Helland Åslaug , Solberg Steinar , Lund-Iversen Marius , Buettner Reinhard , Wolf Jürgen , Brambilla Elisabeth , Vingron Martin , Perner Sven , Haas Stefan A , Thomas Roman K 
Published: January 2015

AbstractGenomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline) (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondary rearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8.
Quantification of cell identity from single-cell gene expression profiles
Authors: Efroni Idan , Ip Pui-Leng , Nawy Tal , Mello Alison , Birnbaum Kenneth D 
Published: January 2015

AbstractThe definition of cell identity is a central problem in biology. While single-cell RNA-seq provides a wealth of information regarding cell states, better methods are needed to map their identity, especially during developmental transitions. Here, we use repositories of cell type-specific transcriptomes to quantify identities from single-cell RNA-seq profiles, accurately classifying cells from Arabidopsis root tips and human glioblastoma tumors. We apply our approach to single cells captured from regenerating roots following tip excision. Our technique exposes a previously uncharacterized transient collapse of identity distant from the injury site, demonstrating the biological relevance of a quantitative cell identity index.
Epidemiology and management of gout in Taiwan: a nationwide population study
Authors: Kuo Chang-Fu , Grainge Matthew J , See Lai-Chu , Yu Kuang-Hui , Luo Shue-Fen , Zhang Weiya , Doherty Michael 
Published: January 2015

Abstract
Introduction
Gout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be ‘cured’. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan.

Methods
The National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined.

Results
Of 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was −0.7% (95% CI, −1.7% to 0.3%; P = 0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was −13.4 (95% CI, −16.1 to −10.6) between 2005 and 2007 and −2.1 (95% CI, −10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, −3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan.

Conclusions
In Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT.
Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization
Authors: Lin Ying-Cing , Huang Duen-Yi , Wang Jang-Shiun , Lin Yi-Ling , Hsieh Shie-Liang , Huang Kuo-Chin , Lin Wan-Wan 
Published: January 2015

Abstract
NLRP3 is the most crucial member of the NLR family, as it detects the existence of pathogen invasion and self-derived molecules associated with cellular damage. Several studies have reported that excessive NLRP3 inflammasome-mediated caspase-1 activation is a key factor in the development of diseases. Recent studies have reported that Syk is involved in pathogen-induced NLRP3 inflammasome activation; however, the detailed mechanism linking Syk to NLRP3 inflammasome remains unclear. In this study, we showed that Syk mediates NLRP3 stimuli-induced processing of procaspase-1 and the consequent activation of caspase-1. Moreover, the kinase activity of Syk is required to potentiate caspase-1 activation in a reconstituted NLRP3 inflammasome system in HEK293T cells. The adaptor protein ASC bridges NLRP3 with the effector protein caspase-1. Herein, we find that Syk can associate directly with ASC and NLRP3 by its kinase domain but interact indirectly with procaspase-1. Syk can phosphorylate ASC at Y146 and Y187 residues, and the phosphorylation of both residues is critical to enhance ASC oligomerization and the recruitment of procaspase-1. Together, our results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases.
Eustatic controls on stratigraphy, chemostratigraphy, and water mass evolution preserved in a Lower Permian mudrock succession, Delaware Basin, west Texas, USA
Authors: Nance Hardie S. , Rowe Harry 
Published: January 2015

Bone Spring (Leonardian) mudrock successions in Delaware Basin vary between silica- and carbonate-rich facies marking depositional responses to sea-level changes. Increased Mo, [Formula: see text], and total organic carbon (TOC) record reduced oxygenation during sea-level lowstands. In a 91.4-m (300 ft) core from Sun No. 1 Houssels well and a 39.6-m (130 ft) core from Shell No. 1 Marsden well (Reeves Co., Texas), lower Bone Spring cycles comprised siliceous-calcareous mudrock couplets. The Marsden core was correlative to the upper part of the Houssels core. Cyclicity was interpreted from mineralogical calculations at numerous core horizons using energy-dispersive X-ray fluorescence (ED-XRF) measurements of elemental content. Elemental abundances enabled predicting mineralogy based on the stoichiometric relationships between elements and dominant minerals (calcite and quartz), and from average values of Si and K in published illite analyses. The average sample spacing for ED-XRF measurements was 0.24 m (0.8 ft) for the Houssels core and 0.15 m (0.5 ft) for the Marsden core. The measurements and interpretations provided: (1) information regarding comparisons in stratigraphic and geographic development of facies over the 10-km (6.2-mi) distance between wells and (2) guidance for petrographic, scanning electron micrograph, and organic matter analyses that address processes that produced different facies. Greater carbonate abundance in the Houssels core reflected the proximity to carbonate shelves on the Central Basin Platform (CBP); the greater siliciclastic abundance in the Marsden core was thought to reflect the greater distance from the CBP. Redox element (S and Mo) and TOC concentrations were greater, and [Formula: see text] values were higher in some siliciclastic-dominated intervals, suggesting that anoxia characterized sea-level lowstands when normal marine water flowing from the Panthalassa Ocean was inhibited through narrow interbasin channels or over sills. Carbon isotope ([Formula: see text]) variations suggested changes in organic matter characteristics, whereby greater [Formula: see text]-depleted organic matter was deposited during sea-level lowstands, marking: (1) reduction of shallow-marine sources or (2) increased terrigenous organic carbon contributions.
Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
Authors: Kaufman Peter A. , Awada Ahmad , Twelves Chris , Yelle Louise , Perez Edith A. , Velikova Galina , Olivo Martin S. , He Yi , Dutcus Corina E. , Cortes Javier 
Published: January 2015

Purpose This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.
CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer
Authors: Pivot Xavier , Manikhas Alexey , Żurawski Bogdan , Chmielowska Ewa , Karaszewska Boguslawa , Allerton Rozenn , Chan Stephen , Fabi Alessandra , Bidoli Paolo , Gori Stefania , Ciruelos Eva , Dank Magdolna , Hornyak Lajos , Margolin Sara , Nusch Arnd , Parikh Roma , Nagi Fareha , DeSilvio Michelle , Santillana Sergio , Swaby Ramona F. , Semiglazov Vladimir 
Published: January 2015

Purpose CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. Patients and Methods Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m2 per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m2 per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). Results The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, −1.6%; 95% CI, −2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. Conclusion CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.
Phase I Dose-Escalation Trial of Checkpoint Kinase 1 Inhibitor MK-8776 As Monotherapy and in Combination With Gemcitabine in Patients With Advanced Solid Tumors
Authors: Daud Adil I. , Ashworth Michelle T. , Strosberg Jonathan , Goldman Jonathan W. , Mendelson David , Springett Gregory , Venook Alan P. , Loechner Sabine , Rosen Lee S. , Shanahan Frances , Parry David , Shumway Stuart , Grabowsky Jennifer A. , Freshwater Tomoko , Sorge Christopher , Kang Soonmo Peter , Isaacs Randi , Munster Pamela N. 
Published: January 2015

Purpose We determined the safety, pharmacokinetics, pharmacodynamics, and recommended phase II dose of MK-8776 (SCH 900776), a potent, selective checkpoint kinase 1 (Chk1) inhibitor, as monotherapy and in combination with gemcitabine in a first-in-human phase I clinical trial in patients with advanced solid tumor malignancies. Patients and Methods Forty-three patients were treated by intravenous infusion with MK-8776 at seven dose levels ranging from 10 to 150 mg/m2 as monotherapy and then in combination with gemcitabine 800 mg/m2 (part A, n = 26) or gemcitabine 1,000 mg/m2 (part B, n = 17). Forty percent of patients had three or more prior treatment regimens, and one third of patients had previously received gemcitabine. Results As monotherapy, MK-8776 was well tolerated, with QTc prolongation (19%), nausea (16%), fatigue (14%), and constipation (14%) as the most frequent adverse effects. Combination therapy demonstrated a higher frequency of adverse effects, predominantly fatigue (63%), nausea (44%), decreased appetite (37%), thrombocytopenia (32%), and neutropenia (24%), as well as dose-related, transient QTc prolongation (17%). The median number of doses of MK-8776 administered was five doses, with relative dose-intensity of 0.96. Bioactivity was assessed by γ-H2AX ex vivo assay. Of 30 patients evaluable for response, two showed partial response, and 13 exhibited stable disease. Conclusion MK-8776 was well tolerated as monotherapy and in combination with gemcitabine. Early evidence of clinical efficacy was observed. The recommended phase II dose is MK-8776 200 mg plus gemcitabine 1,000 mg/m2 on days 1 and 8 of a 21-day cycle.
Anxiety and Health-Related Quality of Life Among Patients With Low–Tumor Burden Non-Hodgkin Lymphoma Randomly Assigned to Two Different Rituximab Dosing Regimens: Results From ECOG Trial E4402 (RESORT)
Authors: Wagner Lynne I. , Zhao Fengmin , Hong Fangxin , Williams Michael E. , Gascoyne Randy D. , Krauss John C. , Advani Ranjana H. , Go Ronald S. , Habermann Thomas M. , Leach Joseph W. , O'Connor Brian , Schuster Stephen J. , Cella David , Horning Sandra J. , Kahl Brad S. 
Published: January 2015

Purpose The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients and Methods Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Results Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. Conclusion Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.
Extreme Nonfasting Remnant Cholesterol vs Extreme LDL Cholesterol as Contributors to Cardiovascular Disease and All-Cause Mortality in 90000 Individuals from the General Population
Authors: Varbo Anette , Freiberg Jacob J , Nordestgaard Børge G 
Published: January 2015

Abstract

BACKGROUND
Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality.

METHODS
We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died.

RESULTS
Compared with participants with nonfasting remnant cholesterol &lt;0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1–1.5) for remnant cholesterol of 0.5–0.99 mmol/L (19.3–38.2 mg/dL) to 2.4 (1.9–2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend &lt;0.001). Compared with participants with LDL cholesterol &lt;3.0 mmol/L (115.8 mg/dL), hazard ratios for IHD ranged from 1.3 (1.1–1.5) for LDL cholesterol of 3–3.99 mmol/L (115.8–154 mg/dL) to 2.3 (1.9–2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P &lt; 0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4–2.3) to 3.4 (2.5–4.8) for remnant cholesterol (P &lt; 0.001), and from 1.7 (1.4–2.2) to 4.7 (3.5–6.3) for LDL cholesterol (P &lt; 0.001). Nonfasting remnant cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9–1.1) to 1.6 (1.4–1.9) (P &lt; 0.001), whereas LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7–0.8) to 0.9 (0.8–1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality.

CONCLUSIONS
Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk.
Brain Tumor Mutations Detected in Cerebral Spinal Fluid
Authors: Pan Wenying , Gu Wei , Nagpal Seema , Gephart Melanie Hayden , Quake Stephen R 
Published: January 2015

Abstract

BACKGROUND
Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood–brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative “liquid biopsy” of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined.

METHODS
We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease.

RESULTS
We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from &lt;5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations from the CSF of a patient with leptomeningeal disease by use of cancer panel sequencing, and the result was concordant with genetic testing on the primary tumor biopsy.

CONCLUSIONS
Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care.