bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tectonic Evolution of the Eastern Black Sea and Caucasus: an introduction
Authors: Sosson Marc , Stephenson Randell , Adamia Shota 
Published: June 2017

Abstract
This Special Publication presents the results of 15 different studies in the Black Sea–Caucasus segment of the Alpine–Tethys orogenic realm. The main focus of these studies is the style and timing of key tectonic events occurring primarily during the area's post-Pangaean evolution. The methodologies encompass: geophysics, including active and passive crustal-scale seismology and common depth point reflection seismic profiling (both onshore and marine), palaeomagnetism and magnetostratigraphy; field geology, including biostratigraphic recorrelation; radiochronology; igneous rock geochemistry, including analyses of the obducted ophiolites; and low-temperature thermochronology. The geological record of the area is essentially one of sedimentary basins formed in an extensional back-arc setting and their subsequent compressional deformation during the closure of at least two branches of the Neotethys Ocean system.
Age or ischemia uncouples the blood flow response, tissue acidosis, and direct current potential signature of spreading depolarization in the rat brain
Authors: Menyhárt Ákos , Zölei-Szénási Dániel , Puskás Tamás , Makra Péter , Bari Ferenc , Farkas Eszter 
Published: June 2017

Spreading depolarization (SD) events contribute to lesion maturation in the acutely injured human brain. Neurodegeneration related to SD is thought to be caused by the insufficiency of the cerebral blood flow (CBF) response; yet the mediators of the CBF response, or their deficiency in the aged or ischemic cerebral cortex, remain the target of intensive research. Here, we postulated that tissue pH effectively modulates the magnitude of hyperemia in response to SD, the coupling of which is prone to be dysfunctional in the aged or ischemic cerebral cortex. To test this hypothesis, we conducted systematic correlation analysis between the direct current (DC) potential signature of SD, SD-associated tissue acidosis, and hyperemic element of the CBF response in the isoflurane-anesthetized, young or old, and intact or ischemic rat cerebral cortex. The data demonstrate that the amplitude of the SD-related DC potential shift, tissue acidosis, and hyperemia are tightly coupled in the young intact cortex; ischemia and old age uncouples the amplitude of hyperemia from the amplitude of the DC potential shift and acidosis; the duration of the DC potential shift, hyperemia and acidosis positively correlate under ischemia alone; and old age disproportionally elongates the duration of acidosis with respect to the DC potential shift and hyperemia under ischemia. The coincidence of the variables supports the view that local CBF regulation with SD must have an effective metabolic component, which becomes dysfunctional with age or under ischemia. Finally, the known age-related acceleration of ischemic neurodegeneration may be promoted by exaggerated tissue acidosis.NEW & NOTEWORTHY The hyperemic element of the cerebral blood flow response to spreading depolarization is effectively modulated by tissue pH in the young intact rat cerebral cortex. This coupling becomes dysfunctional with age or under ischemia, and tissue acidosis lasts disproportionally longer in the aged cortex, making the tissue increasingly more vulnerable.
Making the Case for Investment in Rural Cancer Control: An Analysis of Rural Cancer Incidence, Mortality, and Funding Trends
Authors: Blake Kelly D. , Moss Jennifer L. , Gaysynsky Anna , Srinivasan Shobha , Croyle Robert T. 
Published: June 2017

Abstract
Estimates of those living in rural counties vary from 46.2 to 59 million, or 14% to 19% of the U.S. population. Rural communities face disadvantages compared with urban areas, including higher poverty, lower educational attainment, and lack of access to health services. We aimed to demonstrate rural–urban disparities in cancer and to examine NCI-funded cancer control grants focused on rural populations. Estimates of 5-year cancer incidence and mortality from 2009 to 2013 were generated for counties at each level of the rural–urban continuum and for metropolitan versus nonmetropolitan counties, for all cancers combined and several individual cancer types. We also examined the number and foci of rural cancer control grants funded by NCI from 2011 to 2016. Cancer incidence was 447 cases per 100,000 in metropolitan counties and 460 per 100,000 in nonmetropolitan counties (P &lt; 0.001). Cancer mortality rates were 166 per 100,000 in metropolitan counties and 182 per 100,000 in nonmetropolitan counties (P &lt; 0.001). Higher incidence and mortality in rural areas were observed for cervical, colorectal, kidney, lung, melanoma, and oropharyngeal cancers. There were 48 R- and 3 P-mechanism rural-focused grants funded from 2011 to 2016 (3% of 1,655). Further investment is needed to disentangle the effects of individual-level SES and area-level factors to understand observed effects of rurality on cancer. Cancer Epidemiol Biomarkers Prev; 26(7); 992–7. ©2017 AACR.
The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium
Authors: Nichols Hazel B. , Schoemaker Minouk J. , Wright Lauren B. , McGowan Craig , Brook Mark N. , McClain Kathleen M. , Jones Michael E. , Adami Hans-Olov , Agnoli Claudia , Baglietto Laura , Bernstein Leslie , Bertrand Kimberly A. , Blot William J. , Boutron-Ruault Marie-Christine , Butler Lesley , Chen Yu , Doody Michele M. , Dossus Laure , Eliassen A. Heather , Giles Graham G. , Gram Inger T. , Hankinson Susan E. , Hoffman-Bolton Judy , Kaaks Rudolf , Key Timothy J. , Kirsh Victoria A. , Kitahara Cari M. , Koh Woon-Puay , Larsson Susanna C. , Lund Eiliv , Ma Huiyan , Merritt Melissa A. , Milne Roger L. , Navarro Carmen , Overvad Kim , Ozasa Kotaro , Palmer Julie R. , Peeters Petra H. , Riboli Elio , Rohan Thomas E. , Sadakane Atsuko , Sund Malin , Tamimi Rulla M. , Trichopoulou Antonia , Vatten Lars , Visvanathan Kala , Weiderpass Elisabete , Willett Walter C. , Wolk Alicja , Zeleniuch-Jacquotte Anne , Zheng Wei , Sandler Dale P. , Swerdlow Anthony J. 
Published: June 2017

AbstractBreast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360–9. ©2017 AACR.
Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer
Authors: Schøler Lone V. , Reinert Thomas , Ørntoft Mai-Britt W. , Kassentoft Christine G. , Árnadóttir Sigrid S. , Vang Søren , Nordentoft Iver , Knudsen Michael , Lamy Philippe , Andreasen Ditte , Mortensen Frank V. , Knudsen Anders R. , Stribolt Katrine , Sivesgaard Kim , Mouritzen Peter , Nielsen Hans J. , Laurberg Søren , Ørntoft Torben F. , Andersen Claus L. 
Published: June 2017

Abstract
Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention.
Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period.
Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P &lt; 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman ρ = 0.4).
Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. Clin Cancer Res; 23(18); 5437–45. ©2017 AACR.
Dual Inhibition of HDAC and Tyrosine Kinase Signaling Pathways with CUDC-907 Inhibits Thyroid Cancer Growth and Metastases
Authors: Kotian Shweta , Zhang Lisa , Boufraqech Myriem , Gaskins Kelli , Gara Sudheer Kumar , Quezado Martha , Nilubol Naris , Kebebew Electron 
Published: June 2017

Abstract
Purpose: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer–related deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDAC) regulate cancer initiation and progression. Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response.
Experimental Design: CUDC-907 is a first-in-class compound, functioning as a dual inhibitor of HDACs and the PI3K/AKT pathway. We investigated its antiproliferative effect in vitro and in vivo.
Results: CUDC-907 significantly inhibited cellular proliferation in thyroid cancer cell lines, induced G2–M arrest with decreased levels of the checkpoint regulators cyclin B1, AURKA, AURKB, PLK1, and increased p21 and p27. Treatment induced apoptosis with increased caspase-3/7 activity and decreased survivin levels and decreased cellular migration and invasion. CUDC-907 treatment caused H3 hyperacetylation and decreased HDAC2 expression. HDAC2 was upregulated in ATC and other thyroid cancer histologic subtypes. CUDC-907 treatment reduced both p-AKT and p-ERK1/2 levels. Finally, CUDC-907 treatment, in a metastatic mouse model of thyroid cancer, showed significant inhibition of growth and metastases, and tumors from treated mice had decreased HDAC2 expression, suggesting that this may be a useful biomarker of response.
Conclusions: Dual inhibition of HDAC and the tyrosine kinase signaling pathways with CUDC-907 is a promising treatment strategy for advanced, metastatic thyroid cancer. Clin Cancer Res; 23(17); 5044–54. ©2017 AACR.
Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution
Authors: Gupta Ravi G. , Somer Robert A. 
Published: June 2017

Abstract
High-throughput genomic technologies have revealed a remarkably complex portrait of intratumor heterogeneity in cancer and have shown that tumors evolve through a reiterative process of genetic diversification and clonal selection. This discovery has challenged the classical paradigm of clonal dominance and brought attention to subclonal tumor cell populations that contribute to the cancer phenotype. Dynamic evolutionary models may explain how these populations grow within the ecosystem of tissues, including linear, branching, neutral, and punctuated patterns. Recent evidence in breast cancer favors branching and punctuated evolution driven by genome instability as well as nongenetic sources of heterogeneity, such as epigenetic variation, hierarchal tumor cell organization, and subclonal cell–cell interactions. Resolution of the full mutational landscape of tumors could help reconstruct their phylogenetic trees and trace the subclonal origins of therapeutic resistance, relapsed disease, and distant metastases, the major causes of cancer-related mortality. Real-time assessment of the tumor subclonal architecture, however, remains limited by the high rate of errors produced by most genome-wide sequencing methods as well as the practical difficulties associated with serial tumor genotyping in patients. This review focuses on novel approaches to mitigate these challenges using bulk tumor, liquid biopsies, single-cell analysis, and deep sequencing techniques. The origins of intratumor heterogeneity and the clinical, diagnostic, and therapeutic consequences in breast cancer are also explored. Mol Cancer Res; 15(9); 1127–37. ©2017 AACR.
Associations of Age and Sex With Marfan Phenotype
Authors: Roman Mary J. , Devereux Richard B. , Preiss Liliana R. , Asch Federico M. , Eagle Kim A. , Holmes Kathryn W. , LeMaire Scott A. , Maslen Cheryl L. , Milewicz Dianna M. , Morris Shaine A. , Prakash Siddharth K. , Pyeritz Reed E. , Ravekes William J. , Shohet Ralph V. , Song Howard K. , Weinsaft Jonathan W. , Dietz Harry C. , Habashi Jennifer , Silberbach G. Michael , Bavaria Joseph E. , Milewski Karianna , McDonnell Nazli , Tolunay H. Eser , Desvigne-Nickens Patrice , Tseng Hung , Kroner Barbara L. 
Published: June 2017

Background—
The associations of age and sex with phenotypic features of Marfan syndrome have not been systematically examined in a large cohort of both children and adults.

Methods and Results—

We evaluated 789 Marfan patients enrolled in the National Heart, Lung, and Blood Institute GenTAC (Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry (53% male; mean age 31 [range: 1–86 years]). Females aged ≥15 and males aged ≥16 years were considered adults based on average age of skeletal maturity. Adults (n=606) were more likely than children (n=183) likely to have spontaneous pneumothorax, scoliosis, and striae but were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalence of aortic root dilatation. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood versus adulthood (2% versus 35% and 1% versus 9%, respectively, both
P
<0.0001). Adult males were more likely than females to have aortic root dilatation (92% versus 84%), aortic regurgitation (55% versus 36%), and to have undergone prophylactic aortic root replacement (47% versus 24%), all
P
<0.001. Prevalence of previous aortic dissection tended to be higher in males than females (25% versus 18%,
P
=0.06); 44% of dissections were type B. Type B dissection was strongly associated with previous prophylactic aortic root replacement.

Conclusions—
Pulmonary, skeletal, and aortic complications, but not other phenotypic features, are more prevalent in adults than children in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. Aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially in men and after previous prophylactic aortic root replacement.
Sensory Metrics of Neuromechanical Trust
Authors: Softky William , Benford Criscillia 
Published: June 2017

Today digital sources supply a historically unprecedented component of human sensorimotor data, the consumption of which is correlated with poorly understood maladies such as Internet addiction disorder and Internet gaming disorder. Because both natural and digital sensorimotor data share common mathematical descriptions, one can quantify our informational sensorimotor needs using the signal processing metrics of entropy, noise, dimensionality, continuity, latency, and bandwidth. Such metrics describe in neutral terms the informational diet human brains require to self-calibrate, allowing individuals to maintain trusting relationships. With these metrics, we define the trust humans experience using the mathematical language of computational models, that is, as a primitive statistical algorithm processing finely grained sensorimotor data from neuromechanical interaction. This definition of neuromechanical trust implies that artificial sensorimotor inputs and interactions that attract low-level attention through frequent discontinuities and enhanced coherence will decalibrate a brain's representation of its world over the long term by violating the implicit statistical contract for which self-calibration evolved. Our hypersimplified mathematical understanding of human sensorimotor processing as multiscale, continuous-time vibratory interaction allows equally broad-brush descriptions of failure modes and solutions. For example, we model addiction in general as the result of homeostatic regulation gone awry in novel environments (sign reversal) and digital dependency as a sub-case in which the decalibration caused by digital sensorimotor data spurs yet more consumption of them. We predict that institutions can use these sensorimotor metrics to quantify media richness to improve employee well-being; that dyads and family-size groups will bond and heal best through low-latency, high-resolution multisensory interaction such as shared meals and reciprocated touch; and that individuals can improve sensory and sociosensory resolution through deliberate sensory reintegration practices. We conclude that we humans are the victims of our own success, our hands so skilled they fill the world with captivating things, our eyes so innocent they follow eagerly.
Effects of hypoxia and dietary vitamin E on growth performance and oxidative status of Cirrhinus mrigala (Ham., 1822)
Authors: Varghese Tincy , Pal Asim Kumar , Sahu Narottam Prasad , Mishal Puthiyottil , Dasgupta Subrata 
Published: June 2017

Vitamin E is of importance for several physiological processes, some of which also apply to fish. Here, we conducted an experiment to assess the effect of environmental hypoxia and dietary vitamin E on oxidative status and tissue injury in a bottom dwelling carp,Cirrhinus mrigala(Ham., 1822). The four treatments combined oxygen availability (Normoxia/Hypoxua) and Vitamin E presence/absence. Lipid peroxidation parameters such as thiobarbituric acid reactive substances (TBAR), peroxide value (PV), polyunsaturated fatty acids/saturated fatty acid (PUFA/SFA) ratio, catalase (CAT), superoxide dismutase (SOD) and erythrocyte fragility were assessed. The results indicate that exposure to hypoxia elevates these parameters. However, the supplementation of vitamin E via the diet effectively reduced erythrocyte membrane damage (EF) and myeloperoxidase activity (MPO), which were enhanced by the exposure to hypoxia. Dietary vitamin E also improved antioxidant enzyme status in the hypoxia exposed fish, as indicated by the decreased catalase and superoxide dismutase activities. Vitamin E supplementation also compensated for increased levels of peroxide value, thiobarbituric acid reactive substances, and an increased polyunsaturated fatty acids/saturated fatty acid ratio resulting from the exposure to hypoxia. Overall, it can be concluded that fortification of vitamin E in the diet of this carp species, and possibly other fish that live under hypoxic conditions, can restore the antioxidant status and well-being to some extent.
Diagnosis and classification of hematologic malignancies on the basis of genetics
Authors: Taylor Justin , Xiao Wenbin , Abdel-Wahab Omar 
Published: June 2017

Abstract
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1− MPNs, which are largely defined by mutations in JAK2, CALR, or MPL. In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63. Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells.
The NCI Genomic Data Commons as an engine for precision medicine
Authors: Jensen Mark A. , Ferretti Vincent , Grossman Robert L. , Staudt Louis M. 
Published: June 2017

Abstract
The National Cancer Institute Genomic Data Commons (GDC) is an information system for storing, analyzing, and sharing genomic and clinical data from patients with cancer. The recent high-throughput sequencing of cancer genomes and transcriptomes has produced a big data problem that precludes many cancer biologists and oncologists from gleaning knowledge from these data regarding the nature of malignant processes and the relationship between tumor genomic profiles and treatment response. The GDC aims to democratize access to cancer genomic data and to foster the sharing of these data to promote precision medicine approaches to the diagnosis and treatment of cancer.
Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6
Authors: Hill Joshua A. , Magaret Amalia S. , Hall-Sedlak Ruth , Mikhaylova Anna , Huang Meei-Li , Sandmaier Brenda M. , Hansen John A. , Jerome Keith R. , Zerr Danielle M. , Boeckh Michael 
Published: June 2017

Key Points
Inherited ciHHV-6 was detected in 1.4% of HCT recipients and 0.9% of their donors. Acute GVHD grades 2-4 and cytomegalovirus viremia were more frequent when recipients or donors had inherited ciHHV-6.