bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid-Induced Downregulation of ASS1 Contributes to the Maintenance of Intracellular pH in Cancer
Authors: Silberman Alon , Goldman Omer , Boukobza Assayag Odeya , Jacob Adi , Rabinovich Shiran , Adler Lital , Lee Joo Sang , Keshet Rom , Sarver Alona , Frug Julia , Stettner Noa , Galai Sivan , Persi Erez , Halpern Keren Bahar , Zaltsman-Amir Yehudit , Pode-Shakked Ben , Eilam Raya , Anikster Yair , Nagamani Sandesh C.S. , Ulitsky Igor , Ruppin Eytan , Erez Ayelet 
Published: December 2018

Abstract

Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) by either promoter methylation or by HIF1α is associated with increased metastasis and poor prognosis in multiple cancers. We have previously shown that in normoxic conditions, ASS1 downregulation facilitates cancer cell proliferation by increasing aspartate availability for pyrimidine synthesis by the enzyme complex CAD. Here we report that in hypoxia, ASS1 expression in cancerous cells is downregulated further by HIF1α-mediated induction of miR-224-5p, making the cells more invasive and dependent on upstream substrates of ASS1 for survival. ASS1 was downregulated under acidic conditions, and ASS1-depleted cancer cells maintained a higher intracellular pH (pHi), depended less on extracellular glutamine, and displayed higher glutathione levels. Depletion of substrates of urea cycle enzymes in ASS1-deficient cancers decreased cancer cell survival. Thus, ASS1 levels in cancer are differentially regulated in various environmental conditions to metabolically benefit cancer progression. Understanding these alterations may help uncover specific context-dependent cancer vulnerabilities that may be targeted for therapeutic purposes.

Significance:
Cancer cells in an acidic or hypoxic environment downregulate the expression of the urea cycle enzyme ASS1, which provides them with a redox and pH advantage, resulting in better survival.
Molecular Classification of Lymph Node Metastases Subtypes Predict for Survival in Head and Neck Cancer
Authors: Huang Lei , David Odile , Cabay Robert J. , Valyi-Nagy Klara , Macias Virgilia , Zhong Rong , Wenig Barry , Feldman Lawrence , Weichselbaum Ralph , Spiotto Michael T. 
Published: December 2018

AbstractPurpose:In advanced stage head and neck squamous cell cancers (HNSCC), approximately half of the patients with lymph node metastases (LNM) are not cured. Given the heterogeneous outcomes in these patients, we profiled the expression patterns of LNMs to identify the biological factors associated with patient outcomes.Experimental Design: We performed mRNAseq and miRNAseq on 72 LNMs and 29 matched primary tumors from 34 patients with HNSCC. Clustering identified molecular subtypes in LNMs and in primary tumors. Prediction Analysis of Microarrays algorithm identified a 73-gene classifier that distinguished LNM subtypes. Gene-set enrichment analysis identified pathways upregulated in LNM subtypes.Results:Integrative clustering identified three distinct LNM subtypes: (i) an immune subtype (Group 1), (ii) an invasive subtype (Group 2), and (iii) a metabolic/proliferative subtype (Group 3). Group 2 subtype was associated with significantly worse locoregional control and survival. LNM-specific subtypes were not observed in matched primary tumor specimens. In HNSCCs, breast cancers, and melanomas, a 73-gene classifier identified similar Group 2 LNM subtypes that were associated with worse disease control and survival only when applied to lymph node sites, but not when applied to other primary tumors or metastatic sites. Similarly, previously proposed prognostic classifiers better distinguished patients with worse outcomes when applied to the transcriptional profiles of LNMs, but not the profiles of primary tumors.Conclusions:The transcriptional profiles of LNMs better predict outcomes than transcriptional profiles of primary tumors. The LNMs display site-specific subtypes associated with worse disease control and survival across multiple cancer types.
Gastric Focal Neutrophil Infiltration and Wide Duodenal Gastric Foveolar Metaplasia Are Histologic Discriminative Markers for Crohn’s Disease and Behçet’s Disease
Authors: Akemoto Yui , Sakuraba Hirotake , Tanaka Masanori , Hiraga Hiroto , Kikuchi Hidezumi , Morohashi Satoko , Ota Shinji , Hasui Keisuke , Satake Miwa , Watanabe Rina , Tanaka Nahoko , Kawaguchi Shogo , Tatsuta Tetsuya , Sawaya Manabu , Chinda Daisuke , Mikami Tatsuya , Ishiguro Yoh , Kijima Hiroshi , Fukuda Shinsaku 
Published: December 2018

Background/Aims: Behçet’s disease (BD) with intestinal lesions and Crohn’s disease (CD) share clinical features. However, no report has compared the 2 diseases with regard to lesions of the upper gastrointestinal tract (UGT). We aimed to evaluate endoscopic and histologic findings of UGT in CD and BD. Methods: We retrospectively assessed the endoscopic records and biopsy samples of 84 Helicobacter pylori-negative patients (50 CD, 34 BD). In duodenal samples, MUC5AC immunohistochemical analysis was performed to identify gastric foveolar metaplasia. Results: In endoscopic findings, bamboo joint-like appearance (17/50 CD, 0/34 BD) and erosions (14/50 CD, 2/34 BD) were significantly more frequent in CD gastric lesions (p < 0.001, and p = 0.012). In histologic findings of stomach, focal neutrophil infiltration in lamina propria (15/48 CD, 1/34 BD) was significantly more frequent in CD (p < 0.001). In that of duodenum, wide gastric foveolar metaplasia (19/49 CD, 1/34 BD) was significantly more frequent in CD duodenal lesions (p = 0.013). The mean maximum width of the gastric foveolar metaplasia was 114.0 ± 10.6 and 29.5 ± 4.5 μm for CD and BD respectively (p = 0.003). Conclusions: In H. pylori-negative patients, gastric focal neutrophil infiltration and wide duodenal gastric foveolar metaplasia were important for distinguishing CD from BD.
Pesquisando as compositoras brasileiras no século XXI
Authors: Murgel Ana Carolina Arruda de Toledo 
Published: December 2018

O presente artigo foca as motivações, os resultados, a metodologia e a ut i lização da tecnologia, arquivos e fontes na construção e desenvolvimento da pesquisa “Cartografias da canção feminina: compositoras brasileiras do século XX” desenvolvida com apoio da Fundação deAmparo à Pesquisa do Estado de São Paulo (Fapesp) no pós-doutorado em História Cultural no Departamento de História do Instituto de Filosofia e ciências Humanas da Universidade Estadual de Campinas (IFCH/Unicamp).
Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm
Authors: Piacentini Luca , Werba José Pablo , Bono Elisa , Saccu Claudio , Tremoli Elena , Spirito Rita , Colombo Gualtiero Ivanoe 
Published: December 2018

Objective—
Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of large vessel diseases, including abdominal aortic aneurysm (AAA). Herein, we tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA, indicating specific dysfunctions associated with the disease.

Approach and Results—
Using a paired sample design to limit the effects of interindividual variation, we performed a microarray-based investigation of the PVAT transcriptome in 30 patients with AAA, comparing the adipose layer of the dilated abdominal aorta with that of the not-dilated aortic neck in each patient. Furthermore, we used a state-of-the-art data mining procedure to remove the effect of confounders produced by high-throughput gene expression techniques. We found substantial differences in PVAT gene expression clearly distinguishing the dilated from the not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. Comparisons with other adipose depots (omental or subcutaneous fat) confirmed that gene expression changes are locally restricted. We dissected putative mechanisms associated with AAA PVAT dysfunction through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans, and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of the not-dilated aorta.

Conclusions—
Our results support a possible function of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. Interfering with these disease-specific pathways would clarify their precise role in AAA pathogenesis.
Consistency Test of Revealed Comparative Advantage Index: Evidence from India’s Agricultural Export
Authors: Jagdambe Subhash 
Published: December 2018

This article analyses the competitiveness of India’s agricultural products in world markets. Four indices of revealed comparative advantage (RCA) were used at the four-digit level of harmonized system (HS) of classification for the period of 1996–2015. Under live animal products, 7 out of 26 products showed RCA. For vegetable products, 21 out of 58 showed strong RCA. For products like animal or vegetable fat and prepared foodstuff, 2 out of 16 and 9 out of 49 showed RCA, respectively. Further, the consistency tests reveal that the indices are less satisfactory as the cardinal and dichotomous measures but relatively satisfactory as ordinal measure. Hence, study would propose an ordinal interpretation of RCAs indices for better policy formulation. The study has also found the pattern of RCA indices to be fairly stable over the years. JEL Codes: F1, Q1
The Impact of the St. Lawrence Seaway on Marketing Patterns
Authors: Roepke Howard G. 
Published: December 2018

The utilization of the newly improved and expanded St. Lawrence Seaway will occasion major changes in economic activities. It is possible, and indeed has become almost a parlor game, to make differing estimates of the direction and extent of the Seaway's impact. The one certainty is that there WILL be an impact. This impact will inevitably change marketing prospects, both internal and external to the United States. As the result of a study recently completed, it is possible to form some estimates of the direction which these changes may take.
The Most Profitable Market Share Objectives
Authors: Slater Charles C. 
Published: December 2018

Both the petroleum industry and food chains face the recurring problem of choosing between a large sales volume at relatively low profit margins, and a lower sales volume at a current higher profit margin. In this article, the author discusses selected marketing studies in which it was possible to estimate the “optimum” market share under various competitive conditions. The underlying principles may have wide application for marketing planners.
The Future of Research in Marketing: Marketing Science
Authors: Bass Frank M. 
Published: December 2018

This February 1993 issue begins the 30th Anniversary volume of the Journal of Marketing Research. The academic marketing discipline, as reflected in the articles published in JMR, has certainly changed dramatically over this time period. To reflect on these changes and generate discussion about the future directions for marketing research, I have asked several marketing scholars to prepare guest editorials. It is fitting that Frank Bass write the first of these guest editorials. Professor Bass is a former editor of the JMR and a recipient of the William O'Dell Award for the best paper published in JMR, the Paul D. Converse Award for outstanding contributions to marketing science and theory, and the Richard D. Irwin/American Marketing Association Distinguished Marketing Educator Award. In addition to his research published in the leading marketing and management science journals. Professor Bass has made significant contributions through his former doctoral students who are professors in leading management schools across the world. —Barton A. Weitz, Editor
The Advantages of Entry in the Growth Stage of the Product Life Cycle: An Empirical Analysis
Authors: Shankar Venkatesh , Carpenter Gregory S. , Krishnamurthi Lakshman 
Published: December 2018

In this article, the authors examine how the stage of product life cycle in which a brand enters affects its sales through brand growth and market response, after controlling for the order-of-entry effect and time in market. The authors develop a dynamic brand sales model in which brand growth and market response parameters vary by stage of life cycle entry, namely, by pioneers, growth-stage entrants, and mature-stage entrants. The authors estimate the model using data on 29 brands from six pharmaceutical markets. The results reveal advantages associated with entering during the growth stage. Growth-stage entrants reach their asymptotic sales level faster than pioneers or mature-stage entrants, are not hurt by competitor diffusion, and enjoy a higher response to perceived product quality than pioneers and mature-stage entrants. Pioneers reach their asymptotic sales levels more slowly than later entrants, and pioneer's sales, unlike later entrants’ sales, are hurt by competitor diffusion over time. On the positive side for pioneers, buyers are most responsive to marketing spending by pioneers. Mature-stage entrants are most disadvantaged; they grow more slowly than growth-stage entrants, have lower response to product quality than growth-stage entrants, and have the lowest response to marketing spending.
Parametric methods for [18F]flortaucipir PET
Authors: Golla Sandeep SV , Wolters Emma E , Timmers Tessa , Ossenkoppele Rik , van der Weijden Chris WJ , Scheltens Philip , Schwarte Lothar , Mintun Mark A , Devous Sr Michael D , Schuit Robert C , Windhorst Albert D , Lammertsma Adriaan A , Yaqub Maqsood , van Berckel Bart NM , Boellaard Ronald 
Published: December 2018

[18F]Flortaucipir is a PET tau tracer used to visualize tau binding in Alzheimer’s disease (AD) in vivo. The present study evaluated the performance of several methods to obtain parametric images of [18F]flortaucipir. One hundred and thirty minutes dynamic PET scans were performed in 10 AD patients and 10 controls. Parametric images were generated using different linearization and basis function approaches. Regional binding potential (BPND) and volume of distribution (VT) values obtained from the parametric images were compared with corresponding values derived using the reversible two-tissue compartment model (2T4k_VB). Performance of SUVr parametric images was assessed by comparing values with distribution volume ratio (DVR) and SRTM-derived BPND estimates obtained using non-linear regression (NLR). Spectral analysis (SA) ( r2 = 0.92; slope = 0.99) derived VT correlated well with NLR-derived VT. RPM ( r2 = 0.95; slope = 0.98) derived BPND correlated well with NLR-derived DVR. Although SUVr80–100 min correlated well with NLR-derived DVR ( r2 = 0.91; slope = 1.09), bias in SUVr appeared to depend on uptake time and underlying level of specific binding. In conclusion, RPM and SA provide parametric images comparable to the NLR estimates. Individual SUVr values are biased compared with DVR and this bias requires further study in a larger dataset in order to understand its consequences.
Junior clinical academic psychiatrists in Australia: The University of New South Wales initiative
Authors: Mohan Adith , Bayes Adam , Sachdev Perminder S , Parker Gordon , Mitchell Philip B 
Published: December 2018

Objective: We examined current pathways of training for junior clinical academic psychiatrists in Australia. An initiative of the School of Psychiatry, University of New South Wales, is described from the perspective of two junior clinical academics. Conclusions: Australia has limited defined clinical academic pathways for psychiatrists when compared internationally. Numerous challenges for junior psychiatrists entering academia include tensions between clinical and academic roles, reduced remuneration, difficulty building a competitive track record and a scarcity of funding. Potential solutions lie with universities and local health districts partnering to fund clinical academic roles and offering flexible entry points across specialty training. Fostering research engagement in junior psychiatrists will develop the next generation of clinical academics with benefit for clinical and academic domains.
Radiographic Results of Unicortical Medial Malleolar Fracture Fixation
Authors: Bäcker Henrik C. , Konigsberg Matthew , Freibott Christina E. , Rosenwasser Melvin P. , Greisberg Justin K. , Vosseller J. Turner 
Published: December 2018

Background: Medial malleolar fractures commonly occur as part of rotational ankle fractures, which often require surgery. Different fixation techniques exist, including unicortical or bicortical lag-screw fixation. Bicortical screws that engage the lateral distal tibia have been noted to be biomechanically superior to unicortical ones with a lower failure rate. The authors of this study have used unicortical screws routinely. This study was initiated to investigate the clinical results of a large series of patients with unicortical medial malleolar fixation. Methods: Patients who underwent unicortical medial malleolar fracture fixation between 2011 and 2017 were reviewed. In total, 461 ankle fractures were identified with a mean follow-up of 11.4 months (range, 3-57), of which 211 had a medial malleolar fracture. Eight patients were excluded as they did not follow up with the treating surgeons after surgery, leaving 203 patients for evaluation. The primary outcome was radiographic union. Any loss of reduction, complication, or subsequent surgery was recorded. Malunion was defined as greater than 2 mm displacement. Results: There were 2 asymptomatic nonunions (1.0%), 1 delayed union that healed using an external bone growth stimulator (0.5%), and 2 malunions of the medial malleolus (1.0%) with 1 asymptomatic. The other patient developed posttraumatic osteoarthritis but has not yet required further surgery. None of these 5 patients required revision medial malleolar surgery. Ultimately, the union rate using unicortical medial malleolar fixation was 99.0% (201/203). Conclusion: Unicortical fixation of medial malleolar fractures resulted in consistently good healing. Even though biomechanical studies have shown that bicortical screws provide stronger fixation, our clinical results indicate that the need for this stronger fixation may be questionable. Level of Evidence: Level IV, retrospective case series.
A Proof-of-Concept Evaluation of JTPc and Tp-Tec as Proarrhythmia Biomarkers in Preclinical Species: A Retrospective Analysis by an HESI-Sponsored Consortium
Authors: Boulay Emmanuel , Abernathy Matthew M. , Chui Ray , Friedrichs Gregory S. , Gendron-Parra Nicolas , Greiter-Wilke Andrea , Guillon Jean-Michel , Koerner John E. , Menard Ariane , Steidl-Nichols Jill , Pierson Jennifer , Pugsley Michael K. , Rossman Eric I. , Strauss David , Troncy Eric , Valentin Jean-Pierre , Wisialowski Todd , Authier Simon 
Published: December 2018

Introduction: Based on the ICH S7B and E14 guidance documents, QT interval (QTc) is used as the primary in vivo biomarker to assess the risk of drug-induced torsades de pointes (TdP). Clinical and nonclinical data suggest that drugs that prolong the corrected QTc with balanced multiple ion channel inhibition (most importantly the l-type calcium, Cav1.2, and persistent or late inward sodium current, Nav1.5, in addition to human Ether-à-go-go-Related Gene [hERG] IKr or Kv11.1) may have limited proarrhythmic liability. The heart rate-corrected J to T-peak (JTpc) measurement in particular may be considered to discriminate selective hERG blockers from multi-ion channel blockers. Methods: Telemetry data from Beagle dogs given dofetilide (0.3 mg/kg), sotalol (32 mg/kg), and verapamil (30 mg/kg) orally and Cynomolgus monkeys given medetomidine (0.4 mg/kg) orally were retrospectively analyzed for effects on QTca, JTpca, and T-peak to T-end covariate adjusted (Tpeca) interval using individual rate correction and super intervals (calculated from 0-6, 6-12, 12-18, and 18-24 hours postdose). Results: Dofetilide and cisapride (IKr or Kv11.1 blockers) were associated with significant increases in QTca and JTpca, while sotalol was associated with significant increases in QTca, JTpca, and Tpeca. Verapamil (a Kv11.1 and Cav1.2 blocker) resulted in a reduction in QTca and JTpca, however, and increased Tpeca. Medetomidine was associated with a reduction in Tpeca and increase in JTpca. Discussion: Results from this limited retrospective electrocardiogram analysis suggest that JTpca and Tpeca may discriminate selective IKr blockers and multichannel blockers and could be considered in the context of an integrated comprehensive proarrhythmic risk assessment.
Coagulation parameters in hyperthyroid cats before and after radioiodine treatment compared with healthy controls
Authors: Cui Yi , Heuser Katharina , Bauer Natali , Neiger Reto 
Published: December 2018

Objectives The aim of the study was to describe the coagulatory state of hyperthyroid cats before and after successful radioiodine therapy (RIT) compared with healthy age-matched controls, using classical coagulation parameters and thromboelastogram (TEG) as a global assessment method. The differences in coagulation activity after RIT, depending on the thyroid hormone (normal vs low total thyroxine [T4]) state, were also evaluated. Methods Fifteen hyperthyroid cats and 10 healthy age-matched controls were recruited. Hyperthyroid cats that remained hyperthyroid 14 days after RIT were excluded. Haematology, biochemistry, T4, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and TEG were assessed in control cats and hyperthyroid cats before and 7 and 14 days after RIT. Two weeks after successful RIT, further comparisons were made between cats with normal T4 vs those with low T4. Results Fourteen days after successful RIT, 7/15 cats had normal T4 and 8/15 had low T4. Thrombocytosis was noted in 6/15 cats after treatment. Fibrinogen was significantly higher ( P <0.001) and PT shorter ( P <0.01) in the hyperthyroid cats compared with the healthy controls and these changes persisted after RIT. Persistent increases in fibrinogen, PT, TEG maximal amplitude and TEG clot rigidity, reflecting clot stability, after RIT primarily occurred in the cats with normal T4. TEG-K (time until preset amplitude of 20 mm is reached) and alpha (α) angle reflected impaired fibrin cross-linking ability prior to RIT, which significantly increased after therapy ( P <0.05). Conclusions and relevance Based on some of the coagulation parameters, cats with hyperthyroidism showed hypercoagulable tendencies, which were mildly increased after RIT, possibly due to transient radiation-induced thyroiditis.