bluuebunny/crossref_metadata_2025_split huggingface dataset:
Greenhouse to icehouse: a biostratigraphic review of latest Devonian–Mississippian glaciations and their global effects
Authors: Lakin J. A. , Marshall J. E. A. , Troth I. , Harding I. C. 
Published: April 2016

Abstract
The latest Devonian–Mississippian interval records the long-term transition from Devonian greenhouse conditions into the Late Palaeozoic Ice Age (LPIA). This transition was punctuated by three short glaciation events in the latest Famennian, mid-Tournaisian and Visean stages, respectively. Primary evidence for glaciation is based on diamictite deposits and striated pavements in South America, Appalachia and Africa. The aim of this review is to assess the primary biostratigraphic and sedimentological data constraining diamictite deposits through this transition. These data are then compared to the wider record of eustasy, mass extinction and isotope stratigraphy in the lower palaeolatitudes. Precise age determinations are vital to integrate high- and low-palaeolatitude datasets, and to understand the glacial control on wider global changes. Palynological techniques currently provide the best biostratigraphic tool to date these glacial deposits and to correlate the effects of glaciation globally. This review highlights a high degree of uncertainty in the known history of early LPIA glaciation as much of the primary stratigraphic data are limited and/or unpublished. Future high-resolution stratigraphic studies are needed to constrain the history of glaciation both spatially and temporally through the latest Devonian and Mississippian.
miR-339-3p Is a Tumor Suppressor in Melanoma
Authors: Weber Claudia E.M. , Luo Chonglin , Hotz-Wagenblatt Agnes , Gardyan Adriane , Kordaß Theresa , Holland-Letz Tim , Osen Wolfram , Eichmüller Stefan B. 
Published: April 2016

Abstract
Determinants of invasion and metastasis in cancer remain of great interest to define. Here, we report the definition of miR-339-3p as a novel tumor suppressive microRNA that blocks melanoma cell invasion without affecting cell survival. miR-339-3p was identified by a comprehensive functional screen of a human miRNA mimetic library in a cell-based assay for invasion by the melanoma cell line A375. miR-339-3p was determined as a strong inhibitor of invasion differentially expressed in melanoma cells and healthy melanocytes. MCL1 was defined as a target for downregulation by miR-339-3p, functioning through direct interaction with the 3′ untranslated region of MCL1 mRNA. Blocking miR-339-3p by an antagomiR was sufficient to increase melanoma cell invasion, an effect that could be phenocopied by RNAi-mediated silencing of MCL1. In vivo studies established that miR-339-3p overexpression was sufficient to decrease lung colonization by A375 melanoma cells in NSG mice, relative to control cells. Overall, our results defined miR-339-3p as a melanoma tumor suppressor, the levels of which contributes to invasive aggressiveness. Cancer Res; 76(12); 3562–71. ©2016 AACR.
Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP
Authors: Hatzl Stefan , Geiger Olivia , Kuepper Maja Kim , Caraffini Veronica , Seime Till , Furlan Tobias , Nussbaumer Erika , Wieser Rotraud , Pichler Martin , Scheideler Marcel , Nowek Katarzyna , Jongen-Lavrencic Mojca , Quehenberger Franz , Wölfler Albert , Troppmair Jakob , Sill Heinz , Zebisch Armin 
Published: April 2016

Abstract
RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of miRNAs within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By using an RKIP 3′-untranslated region luciferase reporter construct with and without mutation or deletion of the putative miR-23a–binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a–binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4,300 primary patient specimens via database retrieval from The Cancer Genome Atlas, we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity. Cancer Res; 76(12); 3644–54. ©2016 AACR.
The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications
Authors: Tan Zheqiong , Luo Xiangjian , Xiao Lanbo , Tang Min , Bode Ann M. , Dong Zigang , Cao Ya 
Published: April 2016

Abstract
PGC1α is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1α is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1α acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors. The characteristic traits of PGC1α in maintaining metabolic homeostasis promote cancer cell survival and tumor metastasis in harsh microenvironments. Not only does PGC1α act as a coactivator, but is also itself controlled by oncogenes and transcription factors. PGC1α and these molecules can form signaling axes that include PML/PGC1α/PPARα, MITF/PGC1α, and PGC1α/ERRα, which are important in regulating metabolic adaptation in specific cancer types. Some of these PGC1α-associated pathways are inherently activated in cancer cells, and others are induced by stress, which enable cancer cells to acquire resistance against therapy. Notably, certain therapeutic-resistant cancer cells are addicted to PGC1α-dependent metabolic activities. Suppression of PGC1α expression resensitizes these cells to therapeutic treatments, which implicates PGC1α as a promising target in cancer molecular classification and therapy. Mol Cancer Ther; 15(5); 774–82. ©2016 AACR.
Dysregulation of WNT5A/ROR2 Signaling Characterizes the Progression of Barrett-Associated Esophageal Adenocarcinoma
Authors: Lyros Orestis , Nie Linghui , Moore Tami , Medda Rituparna , Otterson Mary , Behmaram Behnaz , Mackinnon Alexander , Gockel Ines , Shaker Reza , Rafiee Parvaneh 
Published: April 2016

AbstractThe mechanism underlying the progression of normal esophageal mucosa to esophageal adenocarcinoma remains elusive. WNT5A is a noncanonical WNT, which mainly functions via the receptor tyrosine kinase-like orphan receptor 2 (ROR2), and has an unclear role in carcinogenesis. In this study, we aimed to determine the role of WNT5A/ROR2 signaling in esophageal adenocarcinoma. Analysis of WNT5A and ROR2 expression patterns in healthy controls, Barrett and esophageal adenocarcinoma patients' esophageal clinical specimens as well as in various esophageal cell lines demonstrated a ROR2 overexpression in esophageal adenocarcinoma tissues compared with Barrett and healthy mucosa, whereas WNT5A expression was found significantly downregulated toward esophageal adenocarcinoma formation. Treatment of esophageal adenocarcinoma OE33 cells with human recombinant WNT5A (rhWNT5A) significantly suppressed proliferation, survival, and migration in a dose-dependent fashion. rhWNT5A was found to inhibit TOPflash activity in ROR2 wild-type cells, whereas increased TOPflash activity in ROR2-knockdown OE33 cells. In addition, ROR2 knockdown alone abolished cell proliferation and weakened the migration properties of OE33 cells. These findings support an early dysregulation of the noncanonical WNT5A/ROR2 pathway in the pathogenesis of esophageal adenocarcinoma, with the loss of WNT5A expression together with the ROR2 overexpression to be consistent with tumor promotion.Implications: The dysregulation of WNT5A/ROR2 noncanonical WNT signaling in Barrett-associated esophageal adenocarcinoma introduces possible prognostic markers and novel targets for tailored therapy of this malignancy. Mol Cancer Res; 14(7); 647–59. ©2016 AACR.
Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis
Authors: Farris Joshua C. , Pifer Phillip M. , Zheng Liang , Gottlieb Eyal , Denvir James , Frisch Steven M. 
Published: April 2016

Abstract
Resistance to anoikis is a prerequisite for tumor metastasis. The epithelial-to-mesenchymal transition (EMT) allows tumor cells to evade anoikis. The wound-healing regulatory transcription factor Grainyhead-like 2 (GRHL2) suppresses/reverses EMT, accompanied by suppression of the cancer stem cell (CSC) phenotype and by resensitization to anoikis. Here, the effects of GRHL2 upon intracellular metabolism in the context of reversion of the EMT/CSC phenotype, with a view toward understanding how these effects promote anoikis sensitivity, were investigated. EMT enhanced mitochondrial oxidative metabolism. Although this was accompanied by higher accumulation of superoxide, the overall level of reactive oxygen species (ROS) declined, due to decreased hydrogen peroxide. Glutamate dehydrogenase 1 (GLUD1) expression increased in EMT, and this increase, via the product α-ketoglutarate (α-KG), was important for suppressing hydrogen peroxide and protecting against anoikis. GRHL2 suppressed GLUD1 gene expression, decreased α-KG, increased ROS, and sensitized cells to anoikis.
Implications: These results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations. Mol Cancer Res; 14(6); 528–38. ©2016 AACR.
Development of Human‐Like Advanced Coronary Plaques in Low‐Density Lipoprotein Receptor Knockout Pigs and Justification for Statin Treatment Before Formation of Atherosclerotic Plaques
Authors: Li Yuxin , Fuchimoto Daiichiro , Sudo Mitsumasa , Haruta Hironori , Lin Qing‐Fei , Takayama Tadateru , Morita Shotaro , Nochi Tomonori , Suzuki Shunichi , Sembon Shoichiro , Nakai Michiko , Kojima Misaki , Iwamoto Masaki , Hashimoto Michiko , Yoda Shunichi , Kunimoto Satoshi , Hiro Takafumi , Matsumoto Taro , Mitsumata Masako , Sugitani Masahiko , Saito Satoshi , Hirayama Atsushi , Onishi Akira 
Published: April 2016

Background

Although clinical trials have proved that statin can be used prophylactically against cardiovascular events, the direct effects of statin on plaque development are not well understood. We generated low‐density lipoprotein receptor knockout (
LDLR
−/−
) pigs to study the effects of early statin administration on development of atherosclerotic plaques, especially advanced plaques.

Methods and Results

LDLR
−/−
pigs were generated by targeted deletion of exon 4 of the

LDLR

gene. Given a standard chow diet,
LDLR
−/−
pigs showed atherosclerotic lesions starting at 6 months of age. When 3‐month‐old
LDLR
−/−
pigs were fed a high‐cholesterol, high‐fat (
HCHF
) diet for 4 months (
HCHF
group), human‐like advanced coronary plaques developed. We also fed 3‐month‐old
LDLR
−/−
pigs an
HCHF
diet with pitavastatin for 4 months (Statin Prophylaxis Group). Although serum cholesterol concentrations did not differ significantly between the 2 groups, intravascular ultrasound revealed 52% reduced plaque volume in statin‐treated pigs. Pathological examination revealed most lesions (87%) in the statin prophylaxis group were early‐stage lesions, versus 45% in the
HCHF
diet group (
P
<0.01). Thin‐cap fibroatheroma characterized 40% of the plaques in the
HCHF
diet group versus 8% in the statin prophylaxis group (
P
<0.01), intraplaque hemorrhage characterized 11% versus 1% (
P
<0.01), and calcification characterized 22% versus 1% (
P
<0.01).

Conclusions

Results of our large animal experiment support statin prophylaxis before the occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and ensure lesion stability. In addition, the
LDLR
−/−
pigs we developed represent a large animal model of human‐like advanced coronary plaque suitable for translational research.
Line Vortices and the Vacillation of Langmuir Circulation
Authors: Malarkey J. , Thorpe S. A. 
Published: April 2016

AbstractThree types of breakdown of Langmuir circulation (Lc) are observed, two of which are represented in large-eddy simulation (LES) models, but the third, vacillation, is not. The stability of Lc can be examined by representing the downwind-aligned vortices by line vortices that are subjected to perturbations. Earlier conclusions relating to stability in homogeneous water of infinite depth are found to be in error because no stationary unperturbed state exists. The motion of vortices is examined and shown to be consistent with an explanation of Lc devised by Csanady. Motion of line vortices in water of limited depth or bounded below by a thermocline is examined. The motion replicates some of the features of vacillation observed by Smith in deep water bounded by a thermocline, including its periodicity and fluctuations in the formation of bubble bands. Vortices describe closed orbits within the Langmuir cells. Particle motions in the vacillating Lc pattern exhibit trapping close to the line vortices or near the cell boundaries. Vacillation appears not to have been observed in water of limited depth. Here, the vacillation period is predicted to be longer than the deep-water equivalent and may be too long for vacillations to be detected.
The Utility of Recurrent Laryngeal Nerve Monitoring During Open Pharyngeal Diverticula Procedures
Authors: Coughlan Carolyn A. , Verma Sunil P. 
Published: April 2016

Objectives: The recurrent laryngeal nerve is at risk of injury during open pharyngeal diverticula operations. The utility of recurrent laryngeal nerve (RLN) monitoring during these procedures was investigated. Methods: A retrospective chart review was performed of 8 open pharyngeal diverticulectomies completed between 2009 and 2014. Intraoperative RLN monitoring took place during all operations. Results: Open pharyngectomy and myotomy was successfully performed in all cases. In two cases the RLN was encountered outside of its normal course. The identity of the nerve was confirmed with electrical stimulation and normal EMG response. Vocal fold motion was preserved in all cases. Conclusions: Use of intraoperative nerve monitoring in pharyngeal diverticula procedures may be beneficial, especially during open operations for Killian-Jamieson diverticulum (KJD) and large Zenker diverticulum (ZD), where the RLN is typically encountered outside of its normal course.
Perceived Risk of Low-Back Injury Among Four Occupations
Authors: Snow Chelsea R. , Gregory Diane E. 
Published: April 2016

Objective: This study aimed to assess the perception of risk of low-back injury of individuals from four groups: office/administrative employees, dental workers (dentists/dental hygienists), firefighters, and undergraduate students. Background: The concept of worker’s perception of injury risk has been used to set safe material-handling limits and to determine compliance with health and safety regulations but has not been used to identify perceptual differences among occupations or potential deficiencies in risk awareness. Method: Participants ( N = 232) were presented with eight images of different low-back postures/tasks and were required to rate their perceived magnitude of low-back risk on a scale from 0 ( no risk) to 10 ( extreme risk). Results: Office/administrative and dental workers rated postures higher than firefighters and students. Individuals from all groups perceived kyphotic postures as having a higher low-back risk than lordotic postures. Further, office and dental workers, compared to firefighters and students, perceived sitting postures to have a relatively higher level of risk, likely due to these postures being typically adopted by these individuals at work. No relationship between previous low-back pain and risk rating was observed in this study. Conclusion: Low-back injury risk perception varies between occupations/groups and may be a result of different exposures. Application: The results of this study can potentially be used to implement occupation-specific training programs to ensure that the scientific research regarding low-back injuries is being properly conveyed to employees across all sectors.
Representative bureaucracy: does female police leadership affect gender-based violence arrests?
Authors: Johnston Karen , Houston John 
Published: April 2016

Representative bureaucracy theory postulates that passive representation leads to active representation of minority groups. This article investigates the passive representation of female police officers at leadership levels and the active representation of women vis-a-vis gender-based violence arrest rates in the UK. Much of the extant research on representative bureaucracy is located at street level, with evidence showing that discretionary power of minority bureaucrats can lead to active representation. This article is focused on leadership levels of a public bureaucracy. The empirical research is based upon a panel dataset of female police officers as an independent variable and gender-based violence arrest rates as a dependent variable. The analysis reveals that there is little evidence of active representation of women by female police leadership. Points for practitioners The research offers policy and public service practitioners with empirical evidence to suggest that representation of minorities is mediated by organizational effects in public bureaucracies.
Anomalous intraosseous venous drainage: Bone perforators?
Authors: Ramelet Albert-Adrien , Crebassa Vincent , D′Alotto Carlos , Buero Guillermo , Gillet Jean-Luc , Grenot-Mercier Anne , Küpfer Stefan , Mendoza Erika , Monsallier Jean-Michel , Obermayer Alfred , Pacheco Kenedy , Pros Nicolas , Rastel Didier , Soulié Dominique 
Published: April 2016

Objectives Anomalous intraosseous venous drainage is a rare and almost unknown entity; only 14 cases have been reported in the literature and 4 mentioned in textbooks. We report the characteristics of 35 further cases observed in 32 patients. Method After the presentation of two cases at the congress of the French Society of Phlebology in Paris (2013), 12 colleagues joined to present a large series of so-called bone perforators observed in their practice, all identified with at least a duplex investigation. Results Thirty-two patients suffering from varicose veins and/or skin changes (C2−C6) associated with a bone perforator of the tibia (with bilateral anomalies in three) are reported: 19 females and 13 males, average age 56.9. The majority of the affected legs were symptomatic (30/35). Bone perforator was an isolated finding in 27/35 legs. In three cases, the investigations revealed that the venous reflux in the bone originated from an incompetent posterior tibial vein. Conclusions We suggest the name of “bone perforators” for an anomalous tibial intraosseous venous drainage, feeding varicose veins, and in more advanced stages lipodermatosclerosis and leg ulcers. Most of them were successfully treated with surgery or sclerotherapy.
Comparison of central and local serial CT assessments of metastatic renal cell carcinoma patients in a clinical phase IIB study
Authors: Felsch Moritz , Zaim Souhil , Dicken Volker , Lehmacher Walter , Scheuring Urban J 
Published: April 2016

Background Clinical oncological studies attempt to improve precision of data by central radiological assessments. However, it is unclear, to which extent local and central assessments diverge. Purpose To quantify inter-reader variability and the deviation of local from central radiological assessments of computed tomography (CT) scans. Material and Methods This was a sub-study of a randomized clinical phase IIb trial in metastatic renal cell carcinoma (RCC), comparing first-line sorafenib with interferon-alpha-2a (IFN-α-2a). It analyzed agreements of local with central RECIST CT assessments by Cohen’s kappa (κ), symmetry tests, deviations in waterfall plots, Bland–Altman plots, and parametric survival analyses. Results The concordance between local and central radiologic review was quantified by κ = 0.53. While local assessment yielded progressive disease (PD) in 18.6%, central assessment classified 22.5% of patient time points as PD exhibiting only a partial overlap with the 18.6% The tumor shrinkage rates in waterfall plots were 68.1% in local and 55.8% in central review (57.8% and 59% by Reader 1 and Reader 2). Bland–Altman plots identified a systematic shift of tumor change rates by −7.5% in local compared to central assessments, that may reflect a systematic tendency of more favorable results in local assessments. The discordance between local and central review was reflected by a time to progression (TTP) hazard ratio (HR) of 1.73 ( P = 0.0003). Conclusion These data suggest that central radiologic review may reduce technical measurement variability in clinical trials, which should be scrutinized in future studies compared to a volumetric reference.
PACAP38 dose-response pilot study in migraine patients
Authors: Vollesen Anne Luise Haulund , Guo Song , Ashina Messoud 
Published: April 2016

Background Intravenous infusion of 10 pmol/kg/min pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces migraine-like attacks in migraine patients without aura (MO). Here, we conducted a pilot study and investigated if lower doses of PACAP38 exert similar migraine-inducing abilities. Methods We randomly allocated six MO patients to receive intravenous infusion of 4, 6, and 8 pmol/kg/min of PACAP38 over 20 minutes in a double-blind, three-way cross-over study. Headache and migraine characteristics were recorded during hospital (0–2 hours) and post-hospital (2–13 hours) phases. Results PACAP38 induced migraine-like attacks in one out of six patients with 4 pmol, two out of six patients with 6 pmol and three out of six patients with 8 pmol ( p = 0.368). All patients reported head pain after 8 pmol/kg/min, whereas five of six participants reported head pain after both 4 and 6 pmol/kg/min. We found no difference between the three doses in the AUC for headache intensity over the 12-hour observation period ( p = 0.142). An exploratory analysis showed a significant difference between 4 pmol and 8 pmol ( p = 0.031). Conclusion A trend of a dose-response relationship between dose of PACAP38 and incidence of migraine was observed. We suggest that 10 pmol/kg/min PACAP38 is the most optimal dose to induce migraine-like attacks.