bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability
Authors: Zhang Jian , Li Ying-Qin , Guo Rui , Wang Ya-Qin , Zhang Pan-Pan , Tang Xin-Ran , Wen Xin , Hong Xiao-Hong , Lei Yuan , He Qing-Mei , Yang Xiao-Jing , Sun Ying , Ma Jun , Liu Na 
Published: December 2018

Abstract

Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC.

Significance:
These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
Towards Greater Inclusion in Cancer Genomics Studies
Authors: Huang Franklin W. 
Published: December 2018

Abstract
The study by Jaratlerdsiri and colleagues represents the first whole-genome sequencing study of prostate cancer from men in sub-Saharan Africa. Preliminary findings include a higher tumor mutation burden in these tumors compared with data from other available prostate cancer cohorts. Although larger studies are needed and greater effort and investment to include patients of African ancestry in cancer genomic studies overall, the findings begin to catalog the diversity of prostate cancer genomics in the African population, which has a high burden of disease and mortality from prostate cancer.
See related article by Jaratlerdsiri et al., p. 6736
A Pilot Trial of the Combination of Transgenic NY-ESO-1–reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab
Authors: Nowicki Theodore S. , Berent-Maoz Beata , Cheung-Lau Gardenia , Huang Rong Rong , Wang Xiaoyan , Tsoi Jennifer , Kaplan-Lefko Paula , Cabrera Paula , Tran Justin , Pang Jia , Macabali Mignonette , Garcilazo Ivan Perez , Carretero Ignacio Baselga , Kalbasi Anusha , Cochran Alistair J. , Grasso Catherine S. , Hu-Lieskovan Siwen , Chmielowski Bartosz , Comin-Anduix Begoña , Singh Arun , Ribas Antoni 
Published: December 2018

Abstract

Purpose:
Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.

Patients and Methods:
Freshly prepared autologous NY-ESO-1–specific T-cell receptor (TCR) transgenic lymphocytes were adoptively transferred together with NY-ESO-1 peptide-pulsed DC vaccination in HLA-A2.1–positive subjects alone (ESO, NCT02070406) or with ipilimumab (INY, NCT01697527) in patients with advanced sarcoma or melanoma.

Results:
Six patients were enrolled in the ESO cohort, and four were enrolled in the INY cohort. Four out of six patients treated per ESO (66%), and two out of four patients treated per INY (50%) displayed evidence of tumor regression. Peripheral blood reconstitution with NY-ESO-1–specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsies via TCR sequencing. Multiparametric mass cytometry of transgenic cells demonstrated shifting of transgenic cells from memory phenotypes to more terminally differentiated effector phenotypes over time.

Conclusions:
ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses.
Perivascular Adipocytes Store Norepinephrine by Vesicular Transport
Authors: Ahmad Maleeha F. , Ferland David , Ayala-Lopez Nadia , Contreras G. Andres , Darios Emma , Thompson Janice , Ismail Alexander , Thelen Kyan , Moeser Adam J. , Burnett Robert , Anantharam Arun , Watts Stephanie W. 
Published: December 2018

Objective—
Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).

Approach and Results—
High-performance liquid chromatography identified norepinephrine in normal male Sprague Dawley rat aortic, superior mesenteric artery, and mesenteric resistance vessel PVATs, and retroperitoneal fat. Real-time polymerase chain reaction revealed VMAT1 and VMAT2 mRNA expression in the adipocytes and stromal vascular fraction of mesenteric resistance vessel PVAT. Immunofluorescence demonstrated the presence of VMAT1 and VMAT2, and the colocalization of VMAT2 with norepinephrine, in the cytoplasm of adipocytes in mesenteric resistance vessel PVAT. A protocol was developed to capture real-time uptake of Mini 202—a functional and fluorescent VMAT probe—in live rat PVAT adipocytes. Mini 202 was taken up by freshly isolated and differentiated adipocytes from mesenteric resistance vessel PVAT and adipocytes from thoracic aortic and superior mesenteric artery PVATs. In adipocytes freshly isolated from mesenteric resistance vessel PVAT, addition of rose bengal (VMAT inhibitor), nisoxetine (norepinephrine transporter inhibitor), or corticosterone (organic cation 3 transporter inhibitor) significantly reduced Mini 202 signal. Immunofluorescence supports that neither VMAT1 nor VMAT2 is present in retroperitoneal adipocytes, suggesting that PVAT adipocytes may be unique in storing norepinephrine.

Conclusions—
This study supports a novel function of PVAT adipocytes in storing amines in a VMAT-dependent manner. It provides a foundation for future studies exploring the purpose and mechanisms of norepinephrine storage by PVAT in normal physiology and obesity-related hypertension.
TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia
Authors: Srivastava Roshni , Rolyan Harshvardhan , Xie Yi , Li Na , Bhat Neha , Hong Lingjuan , Esteghamat Fatemehsadat , Adeniran Adebowale , Geirsson Arnar , Zhang Jiasheng , Ge Guanghao , Nobrega Marcelo , Martin Kathleen A. , Mani Arya 
Published: December 2018

Objective—
TCF7L2 (transcription factor 7-like 2) is a Wnt-regulated transcription factor that maintains stemness and promotes proliferation in embryonic tissues and adult stem cells. Mice with a coronary artery disease–linked mutation in Wnt-coreceptor LRP6 (LDL receptor-related protein 6) exhibit vascular smooth muscle cell dedifferentiation and obstructive coronary artery disease, which are paradoxically associated with reduced TCF7L2 expression. We conducted a comprehensive study to explore the role of TCF7L2 in vascular smooth muscle cell differentiation and protection against intimal hyperplasia.

Approach and Results—
Using multiple mouse models, we demonstrate here that TCF7L2 promotes differentiation and inhibits proliferation of vascular smooth muscle cells. TCF7L2 accomplishes these effects by stabilization of GATA6 (GATA-binding protein 6) and upregulation of SM-MHC (smooth muscle cell myosin heavy chain) and cell cycle inhibitors. Accordingly, TCF7L2 haploinsufficient mice exhibited increased susceptibility to injury-induced hyperplasia, while mice overexpressing TCF7L2 were protected against injury-induced intimal hyperplasia compared with wild-type littermates. Consequently, the overexpression of TCF7L2 in LRP6 mutant mice rescued the injury-induced intimal hyperplasia.

Conclusions—
Our novel findings imply cell type-specific functional role of TCF7L2 and provide critical insight into mechanisms underlying the pathogenesis of intimal hyperplasia.
CD36 Enhances Vascular Smooth Muscle Cell Proliferation and Development of Neointimal Hyperplasia
Authors: Yue Hong , Febbraio Maria , Klenotic Philip A. , Kennedy David J. , Wu Yueheng , Chen Shaoxian , Gohara Amira F. , Li Oliver , Belcher Adam , Kuang Bin , McIntyre Thomas M. , Silverstein Roy L. , Li Wei 
Published: December 2018

Objective—
Dysregulated proliferation of vascular smooth muscle cells (VSMC) plays an essential role in neointimal hyperplasia. CD36 functions critically in atherogenesis and thrombosis. We hypothesize that CD36 regulates VSMC proliferation and contributes to the development of obstructive vascular diseases.

Approach and Results—

We found by immunofluorescent staining that CD36 was highly expressed in human vessels with obstructive diseases. Using guidewire-induced carotid artery injury and shear stress–induced intima thickening models, we compared neointimal hyperplasia in
Apoe
−/−
,
Cd36
−/−
/Apoe
−/−
, and CD36 specifically deleted in VSMC (VSMC

cd36

−/−
) mice. CD36 deficiency, either global or VSMC-specific, dramatically reduced injury-induced neointimal thickening. Correspondingly, carotid artery blood flow was significantly increased in
Cd36
−/−
/Apoe
−/−
compared with
Apoe
−/−
mice. In cultured VSMCs from thoracic aorta of wild-type and
Cd36
−/−
mice, we found that loss of CD36 significantly decreased serum-stimulated proliferation and increased cell populations in S phase, suggesting that CD36 is necessary for VSMC S/G2-M-phase transition. Treatment of VSMCs with a TSR (thrombospondin type 1 repeat) peptide significantly increased wild-type, but not
Cd36
−/−
VSMC proliferation. TSR or serum treatment significantly increased cyclin A expression in wild-type, but not in
Cd36
−/−
VSMCs. STAT3 (signal transducer and activator of transcription), which reportedly enhances both VSMC differentiation and maturation, was higher in
Cd36
−/−
VSMCs. CD36 deficiency significantly decreased expression of Col1A1 (type 1 collagen A1 chain) and TGF-β1 (transforming growth factor beta 1), and increased expression of contractile proteins, including calponin 1 and smooth muscle α actin, and dramatically increased cell contraction.

Conclusions—
CD36 promotes VSMC proliferation via upregulation of cyclin A expression that contributes to the development of neointimal hyperplasia, collagen deposition, and obstructive vascular diseases.
Marketing Research Practices and Problems in Japan
Authors: Hirata Junji , Fukushima Akira , Omuro Tsukuru , Shiosaki Masao , Takeda Katsuaki 
Published: December 2018

The rebuilding of Japan's productive facilities following World War II, is widely recognized. Less well known, though, is the role which “modern” marketing methods have played in this development. A case in point is marketing research. Five Japanese marketing researchers relate the progress already made in the application of marketing research in Japan, and several limitations encountered.
The Military Research-and-Development Market
Authors: Weidenbaum Murray L. 
Published: December 2018

The research-and-development activities performed for the U.S. military establishment constitute one of the major growth markets of the American economy. The level of military R&D during 1960—$2½ billion—was about double the amount devoted to the purpose as recently as 1955. This research is also an important indicator of the direction of future military production requirements. This article indicates the nature of the market and some probable future trends.
Marketing Literature Review
Authors: Speck Paul S. 
Published: December 2018

This section is based on a selection of article abstracts from a comprehensive business literature data base. Marketing-related abstracts from over 125 journals (both academic and trade) are reviewed by JM staff. Descriptors for each entry are assigned by JM staff. Each issue of this section represents three months of entries into the data base. JM wishes to thank Data Courier Inc for use of the ABI/INFORM business data base. Each entry has an identifying number. Cross-references appear immediately under each subject heading. Requests for specific articles should be directed to the specific publication named or to Data Courier Inc. (800/626–2823). Abstracts of the articles are contained in the ABI/INFORM data base which is available through many on-line search vendors.
A Multistage Decision Model for Salesforce Management
Authors: Beswick Charles A. , Cravens David W. 
Published: December 2018

Salesforce decisions consist of a series of interrelated processes including (1) determining the role of personal selling in the organization, (2) allocating selling effort to customers, geographic areas, or products, (3) setting salesforce size, (4) designing sales territories, and (5) managing the salesforce. Efforts to develop quantitative models for these decision areas have been hindered by the complex interactions among the areas. Attempts to isolate these decision areas for model simplification have resulted in considerable suboptimization. A multistage decision model is presented which treats the salesforce decision areas as an aggregate decision process consisting of a series of interrelated stages. Model decisions are based on a response function which relates sales in a control unit to the many determinants of performance including potential, workload, company effort, salesman quality and experience, and prior sales history. The use of an extremely fast dynamic programming algorithm for the allocation of selling time to control units is demonstrated and the interaction between model and manager is emphasized. Model output indicates the optimum salesforce size and provides a basis for designing sales territories. Use of the model in forecasting and performance evaluation also is discussed. The model is general in that it can be applied to most companies employing a field salesforce. The results of a promising application are presented. Reaction of sales management in the test firm indicates that model output is very useful in identifying problem areas, evaluating salesmen, and modifying territorial design to achieve the optimal allocation of selling effort.
Brands, Brand Management, and the Brand Manager System: A Critical-Historical Evaluation
Authors: Low George S. , Fullerton Ronald A. 
Published: December 2018

The authors examine the history of brand management by tracing its development in the context of the marketing environment from 1870 to the present. They develop six theses regarding the evolution of brand management and its implications and substantiate them utilizing a historical approach. They demonstrate that the brand manager system originated well after the leadership of branded products was established, it was adopted following a conventional adoption curve pattern, and it has proven quite adaptable to differing firm and marketing environments over the past several decades. They then evaluate its likely fate in today's rapidly changing environment.
Effect of Penalty Minute Rule Change on Injuries and Game Disqualification Penalties in High School Ice Hockey
Authors: Kriz Peter K. , Staffa Steven J. , Zurakowski David , MacAskill Matthew , Kirchberg Tyler , Robert Kyle , Baird Janette , Lockhart Greg 
Published: December 2018

Background: Recent efforts have focused on eliminating dangerous hits in ice hockey. Fair play rule changes have successfully reduced injury risk but have not been widely implemented. Purpose: To determine the effect of a penalty infraction minutes (PIM) rule change in high school boys’ ice hockey on injuries and game disqualification penalties. Study Design: Cohort study; Level of evidence, 3. Methods: Injury data were collected from 2 Rhode Island hospital systems and game/penalty data through the Rhode Island Hockey Coaches Association website. Participants included high school boys’ hockey varsity players aged 13 to 19 years presenting to 5 emergency departments for hockey injuries during 6 seasons (December 2012–April 2018). Rule change for the 2015-2016 season implemented varying suspensions for players accumulating ≥50 PIM and ≥70 PIM during regular season and playoffs. Injuries were classified as body checking or non–body checking related, and injury rates pre– versus post–rule change were compared via the Cochran-Mantel-Haenszel chi-square test with the odds ratio (OR) to measure risk reduction. Results: During the study period, 1762 boys’ high school varsity hockey games were played. Of 134 game-related injuries, 82 (61.2%) were attributable to body checking. The PIM rule change was associated with a significant reduction in all injuries (OR, 0.55; 95% CI, 0.35-0.86; P = .008), concussion/closed head injury (OR, 0.44; 95% CI, 0.23-0.85; P = .012), and combined subgroups of concussion/closed head injury and upper body injury (OR, 0.50; 95% CI, 0.31-0.80; P = .003). Game disqualification penalties per season were not significantly reduced following the rule change, occurring in 5.2% of games before the rule change and 4.4% of games after (OR, 0.84; 95% CI, 0.54-1.31; P = .440). Conclusion: Implementation of a statewide PIM restriction rule change effectively reduced the mean number of game-related injuries per season among high school boys’ hockey varsity players.
Tensions Within the Ministry of Provenance: Reflections on Co-Creating a Research Game Together With Artists
Authors: Wetzel Richard , Bachour Khaled , Flintham Martin 
Published: December 2018

Background. Research games are challenging to design as they seek to fulfil a research agenda as well as work as a game. We have successfully collaborated with a group of artists in a research game about people’s perception of provenance called The Apocalypse of the Ministry of Provenance (MoP). The web-based game ran for 6 months with a total of 1004 players signing up over its lifetime with 490 consenting to their data being used for research purposes. While the game allowed us to answer our provenance-related research questions, in this article we look at the game design process of such a collaborative research game. Aim. The co-creation approach created tensions that had to be carefully negotiated between everyone involved. The purpose of this article is to investigate the nature of these tensions, what has caused them, and how we managed (or failed) to mitigate them. This leads to recommendations for future researchers co-creating a research game with artists. Method. We use the form of a post-mortem reflection on the development of the game, based on our own experiences, a one-hour long interview with the two artists involved, and post-game phone interviews with players (n=8). Results. We identify the following three tensions that had a high impact on the overall process: 1) Translating research questions into engaging gameplay elements; 2) Creation of research-relevant content by artists; 3) Artistic vision conflicting with research agenda. We contextualize these tensions by describing six vignettes concerning our collaboration in rich detail that highlight the salient issues of the overall process and resulting game from different perspectives. Lastly, we present seven mitigation strategies on how to deal with the tensions or prevent them from arising. Conclusions. A collaboration with artists for the purpose of creating a research game is a rewarding but also challenging process. Overcoming the resulting tensions is possible by utilizing mitigation strategies that need to be implemented jointly between researchers and artists to guarantee the success as an engaging research game.
Foot Function in Patients With Surgically Treated Preaxial Polydactyly of the Foot Compared With Age- and Sex-Matched Healthy Controls
Authors: Burger Elise B. , Lalé Shaktie A. , Hovius Steven E. R. , Nieuwenhoven Christianne A. van , Bus Sicco A. 
Published: December 2018

Background: Treatment of preaxial foot polydactyly, a duplication of the first ray, consists of excision of an extra ray, aiming to improve shoe fitting and aesthetic appearance, while maintaining foot function. Currently, the effect of excision on foot function and foot-related patient experiences is unclear. Methods: A cross-sectional comparison between 37 children treated for preaxial foot polydactyly and 37 age- and sex-matched healthy controls was performed. Dynamic foot function was assessed using plantar pressure measurements and static foot characteristics by physical examination. Patient-reported outcomes for foot function and footwear were evaluated, using the Oxford Ankle Foot Questionnaire for Children (score, 0-100). Results: Compared with controls, patients had significantly lower median peak pressures at the hallux (148 kPa [IQR, 98-245] vs 272 kPa [IQR, 205-381], P < .001) and significantly higher peak pressures at the second metatarsal (217 kPa [IQR, 147-338] vs 166 kPa [IQR, 141-235], P = .002) and third to fifth metatarsals (214 kPa [IQR, 147-290] vs 161 kPa [IQR, 135-235], P < .001). Additionally, patients had a more medially deviated hallux, both while seated (15 degrees (IQR, 11-20) vs 12 degrees [IQR, 10-15], P = .001) and standing (20 degrees [IQR, 15-26] vs 18 degrees [IQR, 15-20], P = .001). No significant correlation between peak pressure distribution and hallux deviation was found. Patients reported minimal problems with foot function (87.5 [IQR, 64.6-100]), but distinct problems with footwear use (50.0 [IQR, 25.0-100]). Conclusion: Patients with surgically treated preaxial foot polydactyly had a substantially altered plantar pressure distribution with more lateral foot progression than healthy controls. Although an increased hallux deviation was not related to altered foot function, it seemed to be the reason for the patient-perceived problems with footwear. Level of Evidence: Level III, comparative series.