bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donald Trump et les « Cinq de la Rust Belt »
Authors: High Steven , Mak Ariane 
Published: October 2019

Partout dans le monde désindustrialisé, le désespoir silencieux durant des décennies a laissé place à une révolte ouverte à l’encontre des élites politiques et culturelles. Aux États-Unis du moins, un débat agite les progressistes – définis au sens large comme les « liberal centrists » et les « social democrats » – sur les causes profondes de ce phénomène. Cet article propose de répondre à ces questions en mobilisant le champ interdisciplinaire des deindustrialization studies et en examinant ce que celui-ci peut nous apprendre des racines historiques et des causes sous-jacentes de l’ascension de Donald Trump. Les leçons politiques que nous serons amenés à tirer de l’histoire récente constituent un enjeu de taille.
cAMP Response Element Modulator α Induces Dual Specificity Protein Phosphatase 4 to Promote Effector T Cells in Juvenile-Onset Lupus
Authors: Hofmann Sigrun R. , Mäbert Katrin , Kapplusch Franz , Russ Susanne , Northey Sarah , Beresford Michael W. , Tsokos George C. , Hedrich Christian M. 
Published: October 2019

Abstract
Effector CD4+ T cells with increased IL-17A and reduced IL-2 production contribute to tissue inflammation and organ damage in systemic lupus erythematosus (SLE). Increased expression of the transcription factor cAMP response element modulator (CREM) α promotes altered cytokine expression in SLE. The aim of this study was to investigate CREMα-mediated events favoring effector CD4+ T cells in health and disease. Using CRISPR/Cas9 genome editing and lentiviral transduction, we generated CREMα-deficient and CREMα-overexpressing Jurkat T cells. Gene expression and regulatory events were assessed using luciferase reporter assays and chromatin immunoprecipitation. Interaction between CREMα and p300 was investigated using proximity ligation assays, coimmunoprecipitation, and knockdown of p300. Gene expression profiles of modified cells were compared with CD4+ T cells from patients with juvenile-onset SLE. We show that CREMα induces dual specificity protein phosphatase (DUSP) 4 in effector CD4+ T cells through corecruitment of p300. The transcriptional coactivator p300 mediates histone acetylation at DUSP4, prompting increased gene expression. Using DUSP4 transfection models and genetically modified CREM-deficient and CREMα-overexpressing T cells, we demonstrate the molecular underpinnings by which DUSP4 induces IL-17A while limiting IL-2 expression. We demonstrate that CD4+ T cells from patients with juvenile-onset SLE share phenotypical features with CREMα-overexpressing CD4+ T cells, including increased DUSP4 expression and imbalanced IL-17A and IL-2 production. Taken together, we describe CREMα-mediated mechanisms that involve the transcriptional upregulation of DUSP4, leading to imbalanced cytokine production by effector T cells. Our findings identify the CREMα/DUSP4 axis as a promising candidate in the search for biomarkers and therapeutic targets in SLE.
Role of IL-15 Signaling in the Pathogenesis of Simian Immunodeficiency Virus Infection in Rhesus Macaques
Authors: Okoye Afam A. , DeGottardi Maren Q. , Fukazawa Yoshinori , Vaidya Mukta , Abana Chike O. , Konfe Audrie L. , Fachko Devin N. , Duell Derick M. , Li He , Lum Richard , Gao Lina , Park Byung S. , Skalsky Rebecca L. , Lewis Anne D. , Axthelm Michael K. , Lifson Jeffrey D. , Wong Scott W. , Picker Louis J. 
Published: October 2019

Abstract
Although IL-15 has been implicated in the pathogenic hyperimmune activation that drives progressive HIV and SIV infection, as well as in the generation of HIV/SIV target cells, it also supports NK and T cell homeostasis and effector activity, potentially benefiting the host. To understand the role of IL-15 in SIV infection and pathogenesis, we treated two cohorts of SIVmac239-infected rhesus macaques (RM; Macaca mulatta), one with chronic infection, the other with primary infection, with a rhesusized, IL-15–neutralizing mAb (versus an IgG isotype control) for up to 10 wk (n = 7–9 RM per group). In both cohorts, anti–IL-15 was highly efficient at blocking IL-15 signaling in vivo, causing 1) profound depletion of NK cells in blood and tissues throughout the treatment period; 2) substantial, albeit transient, depletion of CD8+ effector memory T cells (TEM) (but not the naive and central memory subsets); and 3) CD4+ and CD8+ TEM hyperproliferation. In primary infection, reduced frequencies of SIV-specific effector T cells in an extralymphoid tissue site were also observed. Despite these effects, the kinetics and extent of SIV replication, CD4+ T cell depletion, and the onset of AIDS were comparable between anti–IL-15– and control-treated groups in both cohorts. However, RM treated with anti–IL-15 during primary infection manifested accelerated reactivation of RM rhadinovirus. Thus, IL-15 support of NK cell and TEM homeostasis does not play a demonstrable, nonredundant role in SIV replication or CD4+ T cell deletion dynamics but may contribute to immune control of oncogenic γ-herpesviruses.
Made in Nevada: Mark Twain and the Literary Legacy of Place
Authors: Branch Michael P. 
Published: October 2019

Abstract
In this personal essay, environmental humor writer Michael P. Branch considers the influential ways in which Mark Twain represented the natural environment of the Great Basin Desert in his 1872 book Roughing It. While Twain was among the first writers to recognize the captivating beauty of the high desert, he also promoted a view of the desert as barren wasteland—a complex approach that produced a dual vision of the land that remains dominant today. However, while Twain helped to shape impressions of the Nevada landscape, the Nevada desert also helped to shape the writer Twain would become.
Animal Welfare and the Democratic Frontier: Mark Twain's Condemnation of Bullfighting in A Horse's Tale
Authors: Bradshaw Charles C. 
Published: October 2019

Abstract
The animals in A Horse's Tail populate a singular form of sentimental narrative that ties together animal welfare and the American frontier as a larger story of American national identity. Shelley Fisher Fishkin has called attention to Twain's fascination with animal and human emotions and Twain's associated reversal of human intelligence and animal ignorance in his writing. A Horse's Tale follows this dynamic by offering its horse narrator as a pragmatic commentator on human foibles. But Twain also democratizes human compassion toward animals as a progressive outgrowth of a mythological American frontier, fashioning the horse and other western inhabitants as empathetic characters while casting Old World traditions as artificial and inhumane. Twain's ultimate indictment of Spanish bullfighting at the novella's end thus casts animal cruelty as a hierarchical ritual of social conformity while recasting the American frontier as a foundational myth in the animal welfare movement.
Improvement of growth and bacoside production in Bacopa monnieri through induced autotetraploidy with colchicine
Authors: Inthima Phithak , Sujipuli Kawee 
Published: October 2019

Bacopa monnieri is a medicinal herb that is increasing in demand in Thailand. However, the lack of high-bacoside cultivars has limited pharmaceutical utilization and production. Here, chromosome doubling in B. monnieri was attempt to improve biomass and bacoside content in its seedling. Nodal segments were treated with colchicine (0, 0.025, 0.05, 0.075, 0.1, and 0.5% w/v) for 24 or 48 h before transferring to multiple shoot induction medium (1/2 MS medium supplemented with 0.2 mg L−1 BAP). Of 326 tested clones, 18 and 84 were mixoploids and autotetraploids, respectively. The highest autotetraploid-induction percentage (14.6%) was found after treated with 0.5% (w/v) colchicine, and 48 hours exposure. From 28 selected autotetraploid clones, 21 and 13 have significantly higher fresh and dry weight compared to the diploid clone, respectively. The maximum fresh and dry weight of autotetraploid plants was 2.8 and 2.0-time higher than diploid plants, respectively. Moreover, the maximum total bacoside content (1.55 mg plant−1) was obtained from an autotetraploid plant, which was 2.3-fold higher than the level in diploid plants. These novel autotetraploids have the potential to be developed as resources for value-added improvements in the medicinal and pharmaceutical industries.
ZoaTrack - an online tool to analyse and share animal location data: User engagement and future perspectives
Authors: Newman Peggy , Dwyer Ross G. , Belbin Lee , Campbell Hamish A. 
Published: October 2019

ABSTRACT
ZoaTrack.org is a web application for visualising and analysing animal biotelemetry data. This online facility offers a robust set of free and highly accessible tools, which enables the non-specialist and specialist to better manage, store, visualise and analyse animal location data. The majority of the data stored in the facility has been collected by animal-borne satellite biotelemetry devices (i.e. GPS and ARGOS), but other types of individual-based location data (mark-recapture, VHF, Acoustic) have also been uploaded to Zoatrack.org. The platform is in its 8th year and this paper presents a review of the platform’s user metrics and uptake by the research community. We also discuss the challenges in trying to sustain this type of research support facility and opportunities for the future.
The molecular function of kallikrein‐related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer
Authors: Kryza Thomas , Bock Nathalie , Lovell Scott , Rockstroh Anja , Lehman Melanie L. , Lesner Adam , Panchadsaram Janaththani , Silva Lakmali Munasinghage , Srinivasan Srilakshmi , Snell Cameron E. , Williams Elizabeth D. , Fazli Ladan , Gleave Martin , Batra Jyotsna , Nelson Colleen , Tate Edward W. , Harris Jonathan , Hooper John D. , Clements Judith A. 
Published: October 2019

Kallikrein‐related peptidase 14 (KLK14) is one of the several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumor microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analyzed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic, and in vitro assays with the goal to identify substrates, related‐signaling pathways, and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neoadjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression reoccurred in patients who developed castrate‐resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14 substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14‐regulated genes (Interleukin 32, midkine, SRY‐Box 9), particularly an involvement of the mitogen‐activated protein kinase 1 and interleukin 1 receptor pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumors. Additional work is necessary to determine the benefits and implications of targeting/cotargeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment.
Finger Joint Cartilage Evaluated by Semiquantitative Ultrasound Score in Patients With Rheumatoid Arthritis
Authors: Ogura Takehisa , Hirata Ayako , Hayashi Norihide , Imaizumi Chihiro , Ito Hideki , Takenaka Sayaka , Inoue Yuki , Takakura Yuto , Mizushina Kennosuke , Katagiri Takaharu , Kameda Hideto 
Published: October 2019

ObjectiveJoint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. Since joint space narrowing (JSN) is not a direct evaluation of cartilage using radiography, we aimed to examine the validity of ultrasound (US) cartilage evaluation using a semiquantitative method in patients with RA.MethodsWe enrolled 103 patients with RA who were in remission or showing low disease activity and 42 healthy subjects. The cartilage thickness of the bilateral metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the second to fifth fingers was measured by US, and the recorded images were scored semiquantitatively using a scale of 0–2. In addition, the JSN of the corresponding joints was scored using a hand radiograph. The relationships between total cartilage thickness, its semiquantitative score, and JSN score were assessed using Spearman’s rank correlation coefficients.ResultsTotal cartilage thickness was significantly thinner in patients with RA compared to healthy subjects for both the MCP and PIP joints (both P < 0.001). The semiquantitative sum of 16 joints ranged from 2 to 26 (median 8) in patients with RA, which was significantly greater than the 0–11 (median 4) in healthy subjects (P < 0.001). In patients with RA, the semiquantitative score showed a significant negative correlation with cartilage thickness (ρ = −0.64, P < 0.001) and a significant positive correlation with JSN score (ρ = 0.66, P < 0.001). Furthermore, these scores showed a significant correlation with RA disease duration.ConclusionA simplified and direct evaluation of finger joint cartilage damage by semiquantitative US score is valid and useful for patients with RA.
High‐Energy Efficiency Membraneless Flowless Zn–Br Battery: Utilizing the Electrochemical–Chemical Growth of Polybromides
Authors: Lee Ju‐Hyuk , Byun Yearin , Jeong Gyoung Hwa , Choi Chanyong , Kwen Jiyun , Kim Riyul , Kim In Ho , Kim Sang Ouk , Kim Hee‐Tak 
Published: October 2019

AbstractAqueous Zn–Br batteries (ZBBs) offer promising next‐generation high‐density energy storage for energy storage systems, along with distinctive cost effectiveness particularly in membraneless and flowless (MLFL) form. Unfortunately, they generally suffer from uncontrolled diffusion of corrosive bromine components, which cause serious self‐discharge and capacity fade. An MLFL‐ZBB is presented that fundamentally tackles the problem of bromine crossover by converting bromine to the polybromide anion using protonated pyridinic nitrogen doped microporous carbon decorated on graphite felt (NGF). The NGF electrodes efficiently capture bromine and polybromide anions at the abundant protonated nitrogen dopant sites within micropores and facilitate effective conversion of bromine into polybromides through electrochemical–chemical growth mechanism. The MLFL‐ZBBs with NGF exhibit an extraordinary stability over 1000 charge/discharge cycles, with an energy efficiency over 80%, the highest value ever reported among membraneless Zn–Br batteries. Judicious engineering of an atomistically designed nanostructured electrode offers a novel design platform for low cost, high voltage, long‐life cycle aqueous hybrid Zn–Br batteries.
Enantioselective Synthesis of γ‐Functionalized Cyclopentenones and δ‐Functionalized Cycloheptenones Utilizing a Redox‐Relay Heck Strategy
Authors: Yuan Qianjia , Prater Matthew B. , Sigman Matthew S. 
Published: October 2019

AbstractIn this report, the desymmetrization of cyclic enones under relay Heck conditions with an array of aryl boronic acids, alkenyl triflates and indole derivatives is described. This method grants facile access to diverse γ‐functionalized cyclopentenones and δ‐functionalized cycloheptenones. Using this approach, a formal synthesis of (S)‐baclofen was completed in high yield and excellent enantioselectivity.magnified image
Focused Research Infrastructure for Postgraduate Pediatric Emergency Medicine Fellows Increases Dissemination of Scholarly Work
Authors: Cruz Andrea T. , Doughty Cara B. , Hsu Deborah C. , Chumpitazi Corrie E. , Sampayo Esther M. , Meskill Sarah D. , Shah Manish I. 
Published: October 2019

AbstractBackgroundMany fellows in clinically driven subspecialties may have difficulty completing and publishing their scholarly projects due to lack of prior experience in research, selection of projects that are difficult to complete during fellowship, or mentorship challenges. This may be particularly true in pediatric emergency medicine (PEM) because research time may be longitudinally integrated with clinical rotations, rather than blocked as is common in other subspecialties. We describe the creation and outcomes of a structured program to increase academic productivity of PEM fellows.MethodsThis was a retrospective cohort study of scholarly productivity (publications in peer‐reviewed journals, presentation at national meetings) for PEM fellows over 17 years in one fellowship program, before and after the implementation of a structured program. We reviewed obstacles to publication for prior fellow projects when developing the curriculum. Our multifaceted program consisted of milestone development, four in‐person committee meetings, and abstract and manuscript development workshops. We utilized existing faculty members, most of whom were junior faculty, as committee members. Our primary outcome was the percentage of fellows who were first authors for peer‐reviewed publications for their fellowship projects. National conference presentations were the secondary outcome.ResultsData for 76 PEM fellows were eligible for analysis: 44 (58%) before and 32 after programmatic implementation. There was a statistically significant increase in the percentage of fellows who published their studies (32% vs. 63%; odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.4 to 9.3) after programmatic implementation. There were no differences in conference presentations (45% vs. 63%; OR = 2.0, 95% CI = 0.8‐5.1) after implementation.ConclusionsUtilizing a small group of existing, predominantly junior faculty members, we created a structured program that enhanced PEM fellows’ scholarly productivity and increased publications. We believe that this model is sustainable for and generalizable to other PEM fellowship programs.
Purification of hyaluronidase as an anticancer agent inhibiting CD44
Authors: Shakouri Amir , Parvan Reza , Adljouy Nasim , Abdolalizadeh Jalal 
Published: October 2019

AbstractHyaluronidase (Hyal) can be employed to accomplish a diversity of complications related to hyaluronic acid (HA). Hyal contains some classes of catalysts that cleave HA. This enzyme is detected in several human tissues as well as in animal venoms, pathogenic organisms and cancers. Destructive cancer cells regularly increase the CD44 receptor existing in a cell membrane. This receptor acts as an exact receptor for HA, and HA is recognized to motivate the migration, spread, attack and metastasis of cancer cells. Nearly all of the methods used to purify Hyal are highly costly and not proper for industrial applications. This survey aims to review different methods of Hyal purification, which acts as an anticancer agent by degrading HA in tissues and thus inhibiting the CD44–HA interaction. Hyal can be successfully employed in the management of cancer, which is associated with HA–CD44. This review has described different methods for Hyal purification to prepare an origin to develop a novel purification technique for this highly appreciated protein. Using multiple columns is not applicable for the purification of Hyal and thus cannot be used at the industrial level. It is better to use affinity chromatography of anti‐Hyal for Hyal with one‐step purification.
Protein precipitation method for determination of clobazam and N‐desmethylclobazam in human plasma by LC–MS/MS
Authors: Mikayelyan Astghik , Aleksanyan Armine , Sargsyan Mariam , Gevorgyan Arpine , Zakaryan Hasmik , Harutyunyan Armen , Zhamharyan Lusine , Armoudjian Yeghig , Margaryan Tigran 
Published: October 2019

AbstractA protein precipitation method for the determination of clobazam (CLB) and its major active metabolite N‐desmethylclobazam (N‐CLB) in human plasma by liquid chromatography tandem mass spectrometry (LC–MS/MS) was established. CLB and N‐CLB were extracted from human plasma samples by protein precipitation with methanol. Analyte separation was done using a Phenomenex Kinetex™ Biphenyl (50 × 2.1 mm, 1.7 μm) column using isocratic elution with a mobile phase of 5 mm ammonium formate with 0.01% ammonium hydroxide (40%) and methanol (60%) at a flow rate of 0.4 mL/min and an injection volume of 10 μL. The detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode to monitor the precursor‐to‐product ion transitions of m/z 301.1 → 259.0, 306.0 → 263.9 for CLB and CLB‐D5 and 287.0 → 245.0, 292.0 → 250.0 for N‐CLB and N‐CLB‐D5 in positive electrospray ionization mode, respectively. The method was validated over a concentration range of 2.0–750 ng/mL for CLB and 0.7–200 ng/mL for N‐CLB on SCIEX Triple Quad 4500 MS System. Total run time was 5 min. This method has been designed for bioequivalence study for formulations containing 20 mg of CLB.
Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high‐performance liquid chromatography coupled to tandem mass spectrometry
Authors: Mendes Gustavo D. , Pereira Thais da Silva , Rodrigues Júlio César , Santos Elaine Marcílio , Souza Mariani Rafaela , Lopes‐Martins Rodrigo Alvaro Brandão , Antunes Natalícia de Jesus , Moreno Ronilson Agnaldo , De Nucci Gilberto 
Published: October 2019

AbstractTo assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (Cmax), area under curve (AUC), half‐life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69–106.16) for Cmax, 97.44% (90% CI = 91.85–103.37%) for area under curve of plasma concentration until the last concentration observed (AUClast) and 98.30% (90% CI = 92.48–104.49) for the area under curve between the first sample (pre‐dosage) and infinity (AUC0–inf). Since the 90% CI for AUClast, AUC0–inf and Cmax ratios were within the 80–125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.