bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the VA and NIDILRR TBI Model System Cohorts
Authors: Nakase-Richardson Risa , Stevens Lillian Flores , Tang Xinyu , Lamberty Greg J. , Sherer Mark , Walker William C. , Pugh Mary Jo , Eapen Blessen C. , Finn Jacob A. , Saylors Mimi , Dillahunt-Aspillaga Christina , Adams Rachel Sayko , Garofano Jeffrey S. 
Published: July 2017

Objective:
Within the same time frame, compare the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and VA Traumatic Brain Injury Model System (TBIMS) data sets to inform future research and generalizability of findings across cohorts.

Setting:
Inpatient comprehensive interdisciplinary rehabilitation facilities.

Participants:
Civilians, Veterans, and active duty service members in the VA (n = 550) and NIDILRR civilian settings (n = 5270) who were enrolled in TBIMS between August 2009 and July 2015.

Design:
Prospective, longitudinal, multisite study.

Main Measures:
Demographics, Injury Characteristics, Functional Independence Measures, Disability Rating Scale.

Results:
VA and NIDILRR TBIMS participants differed on 76% of comparisons (18 Important, 8 Minor), with unique differences shown across traumatic brain injury etiology subgroups. The VA cohort was more educated, more likely to be employed at the time of injury, utilized mental health services premorbidly, and experienced greater traumatic brain injury severity. As expected, acute and rehabilitation lengths of stay were longer in the VA with no differences in death rate found between cohorts.

Conclusions:
Substantial baseline differences between the NIDILRR and VA TBIMS participants warrant caution when comparing rehabilitation outcomes. A substantive number of NIDILRR enrollees had a history of military service (>13%) warranting further focused study. The TBIMS participant data collected across cohorts can be used to help evidence-informed policy for the civilian and military-related healthcare systems.
Circuit-level Mechanisms of EtOH-dependent dopamine release
Authors: Volo Matteo di , Morozova Ekaterina O. , Lapish Christopher C. , Kuznetsov Alexey , Gutkin Boris 
Published: July 2017

AbstractAlcoholism is the third leading cause of preventable mortality in the world. In the last decades a large body of experimental data has paved the way to a clearer knowledge of the specific molecular targets through which ethanol (EtOH) acts on brain circuits. Yet how these multiple mechanisms play together to result in a dysregulated dopamine (DA) release under alcohol influence remains unclear. In this manuscript, we delineate potential circuit-level mechanisms responsible for EtOH-dependent increase and dysregulation of DA release from the ventral tegmental area (VTA) into nucleus accumbens (Nac). For this purpose, we build a circuit model of the VTA composed of DA and GABAergic neurons, that integrate external Glutamatergic (Glu) inputs to result in DA release. In particular, we reproduced a non-monotonic dose dependence of DA neurons firing activity on EtOH: an increase in firing at small to intermediate doses and a drop below baseline (alcohol-free) levels at high EtOH concentrations. Our simulations predict that a certain level of synchrony is necessary for the firing rate increase produced by EtOH. Moreover, EtOH’s effect on the DA neuron’s firing rate and, consequently, DA release can reverse depending on the average activity level of the Glu afferents to VTA. Further, we propose a mechanism for emergence of transient (phasic) DA peaks and the increase in their frequency in EtOH. Phasic DA transients result from DA neuron population bursts, and these bursts are enhanced in EtOH. These results suggest the role of synchrony and average activity level of Glu afferents to VTA in shaping the phasic and tonic DA release under the acute influence of EtOH and in normal conditions.
The tumor suppressor APC is an attenuator of spindle-pulling forces duringC. elegansasymmetric cell division
Authors: Sugioka Kenji , Fielmich Lars-Eric , Mizumoto Kota , Bowerman Bruce , van den Heuvel Sander , Kimura Akatsuki , Sawa Hitoshi 
Published: July 2017

AbstractThe adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/ß-catenin signaling and accurate chromosome segregation, and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show thatC. elegansAPR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of theC. eleganszygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle pulling forces. Our results document a physical basis for spindle-pulling force attenuation, which may be generally used in asymmetric cell division, and when disrupted potentially contributes to division defects in cancer.Significance StatementAPC (adenomatous polyposis coli) is a Wnt signaling component as well as a microtubule-associated protein, and its mutations are frequently associated with colorectal cancers in humans. Although APC stabilizes microtubules (MTs), its mechanical role during cell division is largely unknown. Here we show that APC is an attenuator of forces acting on the mitotic spindle during asymmetric cell division of theC. eleganszygote. We performed live-imaging, laser-microsurgery, and numerical simulation to show how APC suppresses spindle pulling force generation by stabilizing microtubule plus-ends and reducing microtubule catastrophe frequency at the cell cortex. Our study is the first to document a mechanical role for the APC protein, and provides a physical basis for spindle-pulling force attenuation.
Genomic footprints of activated telomere maintenance mechanisms in cancer
Authors: Sieverling Lina , Hong Chen , Koser Sandra D. , Ginsbach Philip , Kleinheinz Kortine , Hutter Barbara , Braun Delia M. , Cortés-Ciriano Isidro , Xi Ruibin , Kabbe Rolf , Park Peter J. , Eils Roland , Schlesner Matthias , Rippe Karsten , Jones David T.W. , Brors Benedikt , Feuerbach Lars ,   on behalf of the PCAWG Structural Variation Working Group, PCAWG SNV Calling Working Group, PCAWG Drivers and Functional Interpretation Group, PCAWG Evolution and Heterogeneity Working Group, PCAWG Technical Working Group, and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: July 2017

AbstractCancers require telomere maintenance mechanisms for unlimited replicative potential. We dissected whole-genome sequencing data of over 2,500 matched tumor-control samples from 36 different tumor types to characterize the genomic footprints of these mechanisms. While the telomere content of tumors withATRXorDAXXmutations (ATRX/DAXXtrunc) was increased, tumors withTERTmodifications showed a moderate decrease of telomere content. One quarter of all tumor samples contained somatic integrations of telomeric sequences into non-telomeric DNA. With 80% prevalence, ATRX/DAXXtrunctumors display a 3-fold enrichment of telomere insertions. A systematic analysis of telomere composition identified aberrant telomere variant repeat (TVR) distribution as a genomic marker of ATRX/DAXXtrunctumors. In this clinically relevant subgroup, singleton TTCGGG and TTTGGG TVRs (previously undescribed) were significantly enriched or depleted, respectively. Overall, our findings provide new insight into the recurrent genomic alterations that are associated with the establishment of different telomere maintenance mechanisms in cancer.
The Influence of Aging and Mechanical Stretch in Alveolar Epithelium ER Stress and Inflammation
Authors: Valentine MS , Herbert JA , Link PA , Kamga Gninzeko F , Schneck MB , Shankar K , Nkwocha J , Reynolds AM , Heise RL 
Published: July 2017

AbstractVentilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is more susceptible to lung injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. An activated response known as Endoplasmic Reticulum (ER) Stress occurs at the cellular level, which is increased with aging. The disrupted ER function results in disruption in cellular homeostasis, apoptosis, and inflammation. We hypothesized that age and mechanical stretch increase proinflammatory gene expression that is mediated by ER stress. Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 8 weeks (young) and 20 months (old) of age. The cells were cyclically mechanically stretched at 15% change in surface area for up to 24 hours. Prior to stretch, groups were administered 4-PBA or vehicle as a control. Mechanical stretch upregulated both ER stress and proinflammatory gene expression in ATIIs. Age-matched and mis-matched monocyte recruitment by ATII conditioned media was quantified. Administration of 4-PBA attenuated both the ER stress and proinflammatory increases from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media. Age increases susceptibility to stretch-induced ER stress and downstream inflammation in a primary ATII epithelial cell model.
Cryptography for genetic material
Authors: Sawaya Sterling 
Published: July 2017

AbstractGenetic information can be highly sensitive and can be used to identify its source. To conceal genetic information, cryptographic methods can be applied to genetic material itself, concealing sensitive information prior to the generation of sequence data. The cryptographic method described here uses randomly divided subsets of barcodes and random pooling to securely generate pools of genetic material. The privacy obtained by these methods are measured here using differential privacy.
GWAS of epigenetic ageing rates in blood reveals a critical role forTERT
Authors: Lu Ake T. , Xue Luting , Salfati Elias L. , Chen Brian H. , Ferrucci Luigi , Levy Daniel , Joehanes Roby , Murabito Joanne M , Kiel Douglas P. , Tsai Pei-Chien , Yet Idil , Bell Jordana T. , Mangino Massimo , Tanaka Toshiko , McRae Allan F. , Marioni Riccardo E. , Visscher Peter M. , Wray Naomi R. , Deary Ian J. , Levine Morgan E. , Quach Austin , Assimes Themistocles , Tsao Philip S. , Absher Devin , Stewart James D. , Li Yun , Reiner Alex P. , Hou Lifang , Baccarelli Andrea A. , Whitsel Eric A. , Aviv Abraham , Cardona Alexia , Day Felix R. , Perry John R.B. , Ong Ken K. , Raj Kenneth , Lunetta Kathryn L. , Horvath Steve 
Published: July 2017

AbstractDNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9,907 individuals, we found gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in 3 loci associated extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggested causal influences of menarche and menopause on IEAA and lipid levels on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) locus at 5p15.33 confer higher IEAA (P<2.7×10-11). Causal modelling indicatesTERT-specific and independent effects on LTL and IEAA. Experimental hTERT expression in primary human fibroblasts engenders a linear increase in DNA methylation age with cell population doubling number. Together, these findings indicate a critical role for hTERT in regulating the DNA methylation clock, in addition to its established role of compensating for cell replication-dependent telomere shortening.
Morphometrics of complex cell shapes: Lobe Contribution Elliptic Fourier Analysis (LOCO-EFA)
Authors: Sánchez-Corrales Yara E. , Hartley Matthew , Rooij Jop van , Marée Athanasius F. M. , Grieneisen Verônica A. 
Published: July 2017

AbstractQuantifying cell morphology is fundamental to the statistical study of cell populations, and can help us unravel mechanisms underlying cell and tissue morphogenesis. Current methods, however, require extensive human intervention, are highly sensitive to parameter choice, or produce metrics that are difficult to interpret biologically. We therefore developed a novel method, Lobe Contribution Elliptical Fourier Analysis (LOCO-EFA), which generates from digitalised cell outlines meaningful descriptors that can be directly matched to morphological features. We show that LOCO-EFA provides a tool to phenotype efficiently and objectively populations of cells by applying it to the complex shaped pavement cells ofArabidopsis thalianawild type andspeechlessleaves. To further validate our method, we analysed computer-generated tissues, where cell shape can be specified in a controlled manner. LOCO-EFA quantifies deviations between the specified shape that an individualin silicocell takes up when in isolation and the resultant shape when they are allowed to interact within a confluent tissue, thereby assessing the role of cell-cell interactions on population cell shape distributions.Summary statementNovel method (LOCO-EFA) quantifies complex cell shapes, extracting meaningful biological features such as protrusion number and amplitude; here shown for plant pavement cells and validated onin silicotissues.
SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasms
Authors: Gu Shengqing , Sayad Azin , Chan Gordon , Yang Wentian , Lu Zhibin , Virtanen Carl , Van Etten Richard A. , Neel Benjamin G. 
Published: July 2017

AbstractBCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia.Ptpn11deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+pre-B cells, but is only required for the proliferation of BCR-ABL1+cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, repressesMXD3/4to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells.
ukbtools: An R package to manage and query UK Biobank data
Authors: Hanscombe Ken B. , Coleman Jonathan R.I , Traylor Matthew , Lewis Cathryn M. 
Published: July 2017

AbstractSummaryThe UK Biobank is a resource that includes detailed health-related data on about 500,000 individuals and is available to the research community. ukbtools removes all the upfront data wrangling required to get a single dataset for statistical analysis, and provides tools to assist in quality control, query of disease diagnoses, and retrieval of genetic metadata.AvailabilityThe package is available for installation from the Comprehensive R Archive Network (CRAN), and includes a vignette describing the use of all functionality.Contact ken.b.hanscombe@kcl.ac.uk,https://github.com/kenhanscombe/ukbtools
Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery
Authors: Hu Yue , Gaedcke Jochen , Emons Georg , Beissbarth Tim , Grade Marian , Jo Peter , Yeager Meredith , Chanock Stephen , Wolff Hendrik , Camps Jordi , Ghadimi B. Michael , Ried Thomas 
Published: July 2017

AbstractBackgroundColorectal cancer (CRC) is among the leading causes of cancer death. Rectal cancers account for one third of CRC cases. The role and significance of colorectal cancer risk loci in rectal cancer progression has not been investigated.MethodsWe generated and explored a dataset from 230 rectal cancer patients by gene expression microarray analysis of cancer samples and matched controls, and SNP arrays of germline DNA.Results8q24 (upstream ofMYC) and 18q21 (in the intron ofSMAD7), two of the loci most strongly linked with colorectal cancer risk, as well as 20q13 (in the intron ofLAMA5), are tightly associated with the prognosis of rectal cancer patients. For SNPs on 18q21 (rs12953717 and rs4464148) and 20q13 (rs4925386), alleles that correlate with higher risk for the development of colorectal cancer are associated with shorter disease free survival. However, for rs6983267 on 8q24, the low risk allele is associated with a higher risk for recurrence and metastasis after surgery, and importantly, is strongly correlated with the resistance of colorectal cancer cell lines to chemoradiotherapy. We also found that althoughMYCexpression is dramatically increased in cancer, patients with higher levels ofMYChave a better prognosis. The expression ofSMAD7is weakly correlated with disease free time. Notably, the presence of the 8q24 and 18q21 SNP alleles is not correlated with a change of expression ofMYCandSMAD7.rs4464148, and probably rs6983267 and rs4925386, are linked with overall survival time of patients.ConclusionsSNPs at three colorectal cancer risk loci detect subpopulations of rectal cancer patients with poor prognosis. rs6983267 probably affects prognosis through interfering with the resistance of cancer cells to chemoradiotherapy.
Kinome rewiring reveals AURKA is a molecular barrier to the efficacy of PI3K/mTOR-pathway inhibitors in breast cancer
Authors: Donnella Hayley J , Webber James T , Levin Rebecca S , Camarda Roman , Momcilovic Olga , Bayani Nora , Korkola James , Shokat Kevan M , Goga Andrei , Gordan John , Bandyopadhyay Sourav 
Published: July 2017

ABSTRACTDysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest. We hypothesized that dynamic changes in signaling, including adaptation and feedback, limit drug efficacy. Using a quantitative chemoproteomics approach we mapped dynamic changes in the kinome in response to various agents and identified signaling changes that correlate with drug sensitivity. Measurement of dynamics across a panel of breast cancer cell lines identified that maintenance of CDK4 and AURKA activity was associated with drug resistance. We tested whether incomplete inhibition of CDK4 or AURKA was a source of therapy failure and found that inhibition of either was sufficient to sensitize most breast cancer cells to PI3K, AKT, and mTOR inhibitors. In particular, drug combinations including the AURKA inhibitor MLN8237 were highly synergistic and induced apoptosis through enhanced suppression of mTOR signaling to S6 and 4E-BP1 leading to tumor regressionin vivo.This signaling map identifies survival factors whose presence limits the efficacy of target therapy and indicates that Aurora kinase co-inhibition could unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer.
Movements and habitat use of the night parrot Pezoporus occidentalis in south‐western Queensland
Authors: Murphy Stephen A. , Silcock Jennifer , Murphy Rachel , Reid Julian , Austin Jeremy J. 
Published: July 2017

AbstractThe nocturnal, cryptic and geographically remote nature of night parrots, combined with their apparent rapid decline, means that very little is known of their biology or ecology. The discovery of a resident population in south‐western Queensland in 2013 provides the first opportunity to undertake detailed studies on this most enigmatic of birds. We attached a radio tag to a bird for 20 days in April 2015 and a GPS tag to another bird for 5 days in May 2016 to study movement patterns and habitat use. Both birds displayed similar behaviour but the GPS‐tagging provided a much finer resolution of spatial data. They called at dusk from their diurnal roosts amongst spinifex hummocks and then flew to more floristically diverse habitats dominated by large‐seeded species to feed. We conducted floristic surveys to describe the feeding grounds of the GPS‐tagged bird and make dietary inferences. This individual spent most of its time in highly diverse but ephemeral habitats, including seasonally inundated plains and depressions associated with the outer Diamantina floodplain and gilgais on ironstone plains. Prolifically seeding ephemeral species, most notably the annual grass Uranthoecium truncatum, dominate these feeding grounds. This work suggests that the habitat mosaic containing roost sites in close proximity to feeding grounds with key seed‐producing species is an important factor, rather than an association with spinifex or samphire alone. Further work is needed to examine movement patterns and habitat use in more typical dry seasons and the impact of cattle grazing on night parrot feeding areas, particularly with regard to seed production. The information presented here is vital for both in situ conservation of the Pullen‐Pullen‐Mt Windsor‐Diamantina population and for setting future research and survey priorities.
Pouch failures following ileal pouch–anal anastomosis for ulcerative colitis
Authors: Mark‐Christensen A. , Erichsen R. , Brandsborg S. , Pachler F. R. , Nørager C. B. , Johansen N. , Pachler J. H. , Thorlacius‐Ussing O. , Kjær M. D. , Qvist N. , Preisler L. , Hillingsø J. , Rosenberg J. , Laurberg S. 
Published: July 2017

AbstractAimIleal pouch–anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure.MethodThe study included 1991 patients with ulcerative colitis who underwent ileal pouch–anal anastomosis in Denmark in the period 1980–2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1–5 cases per year; low, 6–10; intermediate 11–20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis.ResultsOver a median 11.4 years, 295 failures occurred, corresponding to 5‐, 10‐ and 20‐year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10–1.75]. Primary non‐diversion (aHR 1.63, 95% CI 1.11–2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26–4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy.ConclusionIn a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch–anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non‐diversion were associated with a higher risk of pouch failure.