bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors and Stroke Mechanisms in Atherosclerotic Stroke
Authors: Kim Jong S. , Nah Hyun-Wook , Park Sea Mi , Kim Su-Kyung , Cho Ki Hyun , Lee Jun , Lee Yong-Seok , Kim Jei , Ha Sang-Won , Kim Eung-Gyu , Kim Dong-Eog , Kang Dong-Wha , Kwon Sun U. , Yu Kyung-Ho , Lee Byung-Chul 
Published: November 2012

Background and Purpose—
The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis.

Methods—
A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment.

Results—

Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018–1.049), male gender (OR, 3.399; 95% CI, 2.335–4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117–2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274–2.618;
P
=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105–2.010;
P
=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005–5.890;
P
=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (
P
<0.001).

Conclusions—
The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.
Impact of ACE2 Deficiency and Oxidative Stress on Cerebrovascular Function With Aging
Authors: Silva Ricardo A. Peña , Chu Yi , Miller Jordan D. , Mitchell Ian J. , Penninger Josef M. , Faraci Frank M. , Heistad Donald D. 
Published: November 2012

Background and Purpose—
Angiotensin II produces oxidative stress and endothelial dysfunction in cerebral arteries, and angiotensin II type I receptors may play a role in longevity and vascular aging. Angiotensin-converting enzyme type 2 (ACE2) converts angiotensin II to angiotensin (1–7) and thus, may protect against effects of angiotensin II. We hypothesized that ACE2 deficiency increases oxidative stress and endothelial dysfunction in cerebral arteries and examined the role of ACE2 in age-related cerebrovascular dysfunction.

Methods—
Endothelial function, expression of angiotensin system components, NADPH oxidase subunits, and proinflammatory cytokines were examined in cerebral arteries from adult (12 months old) and old (24 months old) ACE2 knockout (KO) and wild-type (WT) mice. The superoxide scavenger tempol was used to examine the role of oxidative stress on endothelial function.

Results—

Vasodilatation to acetylcholine was impaired in adult ACE2 KO (24±6% [mean±SE]) compared with WT mice (52±7%;
P
<0.05). In old mice, vasodilatation to acetylcholine was impaired in WT mice (29±6%) and severely impaired in ACE2 KO mice (7±5%). Tempol improved endothelial function in adult and old ACE2 KO and WT mice. Aging increased mRNA for tumor necrosis factor-α in WT mice, and significantly increased mRNA levels of NAPDH oxidase 2, p47
phox
, and Regulator of calcineurin 1 in both ACE2 KO and WT mice. mRNA levels of angiotensin system components did not change during aging.

Conclusions—
ACE2 deficiency impaired endothelial function in cerebral arteries from adult mice and augmented endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging.
Putting the “We” Into Teamwork
Authors: Ford Jane , O’Hare David , Henderson Robert 
Published: November 2012

Objective: The study was designed to investigate the effectiveness of a manipulation derived from social categorization and social identity theory to promote greater cabin crew willingness to engage in intergroup communication and teamwork in airline operations. Background: Failures of communication and teamwork between airline crew have been implicated in a number of airline crashes. Method: Flight attendants based domestically ( n = 254) or overseas ( n = 230) received a manipulation designed to prime either their social identity or personal identity and then read a brief outline of an in-flight event before completing a teamwork questionnaire. Results: Flight attendants who received a social identity prime indicated increased willingness to engage in coordinated team action compared with those who received a personal identity prime. Conclusion: Priming social identity can enhance attitudes toward teamwork and communication, potentially leading to increased willingness to engage in intergroup cooperation. Application: Social categorization and social identity theories can be used to inform joint training program development for flight attendants and pilots to create increased willingness for group members to participate in effective communication and teamwork behaviors.
The Securitization of Urban Space and the “Rescue” of Downtown Mexico City
Authors: Becker Anne , Müller Markus-Michael 
Published: November 2012

One important feature of the neoliberalization of urban governance around the world has been the rise of an urban entrepreneurialism promoting projects of urban renewal and the upgrading of historic city centers. These developments contribute to an increasing securitization of urban space and the eviction of “undesirables” from the renewed and upgraded areas. An examination of these processes in the implementation of the “rescue” of Mexico City’s historic center and the related securitization of urban space in the neighborhood of La Merced reveals that the implementation and sustainability of this local urban renewal project is constantly challenged and modified by the presence of powerful illegal actors and informal practices of negotiation. Una característica de la neoliberalización de gobernabilidad urbana en el mundo ha sido el acenso de un empresarialismo urbano el cual promueve la renovación urbana y mejoramiento de los centros históricos. Estos procesos contribuyen al incremento de la segurización del espacio urbano y a la expulsión de “indeseables” de la áreas de renovación y mejoramiento. Un examen de estos procesos en la implementación del “rescate” del centro histórico de la Ciudad de México y la relacionada segurización del espacio urbano en el barrio de la Merced pone en relieve que la implementación y sostenibilidad de este proyecto de renovación urbana se encuentra retado constantemente por la presencia de actores ilegales y poderosos y prácticas informales de negociación.
Gender Disparities in Scholarly Productivity within Academic Otolaryngology Departments
Authors: Eloy Jean Anderson , Svider Peter , Chandrasekhar Sujana S. , Husain Qasim , Mauro Kevin M. , Setzen Michael , Baredes Soly 
Published: November 2012

ObjectiveTo examine whether there are gender disparities in scholarly productivity within academic otolaryngology departments, as measured by academic rank and the h‐index, a published, objective measure of research contributions that quantifies the number and significance of papers published by a given author.Study Design and SettingAnalysis of bibliometric data of academic otolaryngologists.MethodsFaculty listings from academic otolaryngology departments were used to determine academic rank and gender. The Scopus database was used to determine h‐index and publication range (in years) of these faculty members. In addition, 20 randomly chosen institutions were used to compare academic otolaryngologists to faculty members in other surgical specialties.ResultsMean h‐indices increased through the rank of professor. Among academic otolaryngologists, men had significantly higher h‐indices than women, a finding also noted on examination of faculty members from other specialties. Men had higher research productivity rates at earlier points in their career than women did. The productivity rates of women increased and equaled or surpassed those of men later in their careers. Men had higher absolute h‐index values at junior academic ranks. Women academic otolaryngologists of senior rank had higher absolute h‐indices than their male counterparts.ConclusionsThe h‐index measures research significance in an objective manner and indicates that although men have higher overall research productivity in academic otolaryngology, women demonstrate a different productivity curve. Women produce less research output earlier in their careers than men do, but at senior levels, they equal or exceed the research productivity of men.
Beneficial role of celery oil in lowering the di(2-ethylhexyl) phthalate-induced testicular damage
Authors: Madkour Naglaa K 
Published: November 2012

Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate in the environment, is known to be a reproductive toxicant. Considering the therapeutic significance of medicinal plants, this study was conducted to evaluate the effects of administration of celery oil on DEHP-induced testicular toxicity. The experiment was carried out for 8 weeks on 36 male rats that were divided equally into six groups. Group 1 was kept as normal control (given vehicle), while rats of group 2 were administered orally 200 mg/kg/day of celery oil. Groups 3 and 5 were orally given 500 and 1000 mg DEHP/kg/day, respectively. Groups 4 and 6 were treated with similar doses of DEHP as in groups 3 and 5 plus celery oil (200 mg/kg/day). Body and testicular weights, sperm parameters, serum hormones (testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol), antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)) and expression of cytochrome P450 aromatase (CYP19) messenger RNA (mRNA) were investigated at the end of 8th week. Treatment with DEHP alone resulted in a significant decrease in body and testicular weights, sperm parameters and serum hormone levels when compared with control. On the other hand, testicular antioxidant enzymes showed a significant dose-dependent increase. The expression of CYP19 mRNA was significantly reduced by increasing the doses of DEHP. Administration of celery oil along with DEHP partially prevented the decrease in body and testicular weights and enhanced epididymal sperm count, serum hormone levels and the expression of CYP19 mRNA along with diminution in the activities of SOD, GPx and CAT enzymes. The obtained results showed that the celery improved the testicular alterations induced by DEHP in albino rats.
Estrogen-Like Disruptive Effects of Dietary Exposure to Bisphenol A or 17α-Ethinyl Estradiol in CD1 Mice
Authors: Kendig Eric L. , Buesing Dana R. , Christie Susie M. , Cookman Clifford J. , Gear Robin B. , Hugo Eric R. , Kasper Susan N. , Kendziorski Jessica A. , Ungi Kevin R. , Williams Karin , Belcher Scott M. 
Published: November 2012

Bisphenol A (BPA) is an endocrine disrupting chemical that is ubiquitous in wild and built environments. Due to variability in study design, the disruptive effects of BPA have proven difficult to experimentally replicate. This study was designed to assess the disruptive actions of dietary BPA exposure, while carefully controlling for known confounders. Parental CD1 mice were acclimated to defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) or 17α-ethinyl estradiol (EE; 0.0001, 0.001, and 0.01 ppm) and bred to produce progeny (F1) that were maintained through adulthood on the same diet as the parents. In F1 females, uterine weights were increased in all EE and the 30-ppm BPA-exposure groups, demonstrating model sensitivity and estrogen-like actions of BPA. In BPA-exposed females, no treatment-related differences were observed in parental reproductive function, or in the timing of puberty and metabolic function in female offspring. In F1 males, modest changes in body weight, adiposity and glucose tolerance, consistent with improved metabolic function, were observed. Associated with increased prolactin and increased circulating testosterone levels, balanopreputial separation was accelerated by 0.03 and 3.0 ppm BPA and anogenital distance at postnatal day 21 was increased in males by 0.03 ppm BPA. Sperm counts were also increased with 3.0 ppm BPA exposures. Overall, BPA was found to have modest, sex specific endocrine disruptive effects on a variety of end points below the established no observed adverse effect level. The dose response characteristics for many of the effects were nonmonotonic and not predictable from high-dose extrapolations.
Impact of prior systemic corticosteroid use in patients admitted with community-acquired pneumonia
Authors: Malave Adriel , Laserna Elena , Sibila Oriol , Mortensen Eric M. , Anzueto Antonio , Restrepo Marcos I. 
Published: November 2012

Background and objective: Limited information is available regarding the impact of prior outpatient use of systemic corticosteroids (SCS) in patients subsequently developing community-acquired pneumonia (CAP). We investigate the effects of prior SCS on severity of illness, microbiology and clinical outcomes for patients hospitalized with CAP. Methods: A retrospective cohort study of subjects with CAP (according to International Classification of Diseases, 9th edition codes) was conducted over a 3-year period at two tertiary teaching hospitals. Subjects were considered to be SCS users if they received oral corticosteroids prior to admission. Primary outcomes were severity of illness, microbiology and 30-day mortality. Results: Data were abstracted on 698 patients [prior SCS users, 75 (10.7%) versus prior non-SCS users 623 (89.3%)]. Prior SCS users were more likely to have chronic obstructive pulmonary disease. No differences were found in severity of disease at admission, microbiological etiology including opportunistic and drug-resistant pathogens and clinical outcomes, including 30-day mortality, intensive care unit admission, length of hospital stay, need for mechanical ventilation and need for vasopressors. Conclusion: Prior SCS use is not associated with increased 30-day mortality for patients hospitalized with CAP. In addition, no differences were found in either the severity of the disease at the time of presentation or in the presence of the resistant or opportunistic pathogens among groups.
Disease-associated missense mutations in the EVH1 domain disrupt intrinsic WASp function causing dysregulated actin dynamics and impaired dendritic cell migration
Authors: Worth Austen J. J. , Metelo Joao , Bouma Gerben , Moulding Dale , Fritzsche Marco , Vernay Bertrand , Charras Guillaume , Cory Giles O. C. , Thrasher Adrian J. , Burns Siobhan O. 
Published: November 2012

AbstractWiskott Aldrich syndrome (WAS), an X-linked immunodeficiency, results from loss-of-function mutations in the human hematopoietic cytoskeletal regulator gene WAS. Many missense mutations in the Ena Vasp homology1 (EVH1) domain preserve low-level WAS protein (WASp) expression and confer a milder clinical phenotype. Although disrupted binding to WASp-interacting protein (WIP) leads to enhanced WASp degradation in vivo, the intrinsic function of EVH1-mutated WASp is poorly understood. In the present study, we show that, despite mediating enhanced actin polymerization compared with wild-type WASp in vitro, EVH1 missense mutated proteins did not support full biologic function in cells, even when levels were restored by forced overexpression. Podosome assembly was aberrant and associated with dysregulated lamellipodia formation and impaired persistence of migration. At sites of residual podosome-associated actin polymerization, localization of EVH1-mutated proteins was preserved even after deletion of the entire domain, implying that WIP-WASp complex formation is not absolutely required for WASp localization. However, retention of mutant proteins in podosomes was significantly impaired and associated with reduced levels of WASp tyrosine phosphorylation. Our results indicate that the EVH1 domain is important not only for WASp stability, but also for intrinsic biologic activity in vivo.
Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature
Authors: Kleinschnitz Christoph , Kraft Peter , Dreykluft Angela , Hagedorn Ina , Göbel Kerstin , Schuhmann Michael K. , Langhauser Friederike , Helluy Xavier , Schwarz Tobias , Bittner Stefan , Mayer Christian T. , Brede Marc , Varallyay Csanad , Pham Mirko , Bendszus Martin , Jakob Peter , Magnus Tim , Meuth Sven G. , Iwakura Yoichiro , Zernecke Alma , Sparwasser Tim , Nieswandt Bernhard , Stoll Guido , Wiendl Heinz 
Published: November 2012

Abstract
We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)–positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1−/− mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.
IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors
Authors: Cieri Nicoletta , Camisa Barbara , Cocchiarella Fabienne , Forcato Mattia , Oliveira Giacomo , Provasi Elena , Bondanza Attilio , Bordignon Claudio , Peccatori Jacopo , Ciceri Fabio , Lupo-Stanghellini Maria Teresa , Mavilio Fulvio , Mondino Anna , Bicciato Silvio , Recchia Alessandra , Bonini Chiara 
Published: November 2012

Abstract
Long-living memory stem T cells (TSCM) with the ability to self-renew and the plasticity to differentiate into potent effectors could be valuable weapons in adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically target this T-cell population remain elusive. Here, we show that it is possible to differentiate in vitro, expand, and gene modify in clinically compliant conditions CD8+ TSCM lymphocytes starting from naive precursors. Requirements for the generation of this T-cell subset, described as CD62L+CCR7+CD45RA+CD45R0+IL-7Rα+CD95+, are CD3/CD28 engagement and culture with IL-7 and IL-15. Accordingly, TSCM accumulates early after hematopoietic stem cell transplantation. The gene expression signature and functional phenotype define this population as a distinct memory T-lymphocyte subset, intermediate between naive and central memory cells. When transplanted in immunodeficient mice, gene-modified naive-derived TSCM prove superior to other memory lymphocytes for the ability to expand and differentiate into effectors able to mediate a potent xenogeneic GVHD. Furthermore, gene-modified TSCM are the only T-cell subset able to expand and mediate GVHD on serial transplantation, suggesting self-renewal capacity in a clinically relevant setting. These findings provide novel insights into the origin and requirements for TSCM generation and pave the way for their clinical rapid exploitation in adoptive cell therapy.
The constitutive androstane receptor is a novel therapeutic target facilitating cyclophosphamide-based treatment of hematopoietic malignancies
Authors: Wang Duan , Li Linhao , Yang Hui , Ferguson Stephen S. , Baer Maria R. , Gartenhaus Ronald B. , Wang Hongbing 
Published: November 2012

AbstractCyclophosphamide (CPA) is one of the most widely used chemotherapeutic prodrugs that undergoes hepatic bioactivation mediated predominantly by cytochrome P450 (CYP) 2B6. Given that the CYP2B6 gene is primarily regulated by the constitutive androstane receptor (CAR, NR1I3), we hypothesize that selective activation of CAR can enhance systemic exposure of the pharmacologically active 4-hydroxycyclophosamide (4-OH-CPA), with improved efficacy of CPA-based chemotherapy. In this study, we have developed a unique human primary hepatocyte (HPH)–leukemia cell coculture model; the chemotherapeutic effects of CPA on leukemia cells can be directly investigated in vitro in a cellular environment where hepatic metabolism was well maintained. Our results demonstrated that activation of CAR preferentially induces the expression of CYP2B6 over CYP3A4 in HPHs, although endogenous expression of these enzymes in leukemia cells remains negligible. Importantly, coadministration of CPA with a human CAR activator led to significantly enhanced cytotoxicity in leukemia cells by inducing the apoptosis pathways, without concomitant increase in the off-target hepatotoxicity. Associated with the enhanced antitumor activity, a time and concentration-dependent increase in 4-OH-CPA formation was observed in the coculture system. Together, our findings offer proof of concept that CAR as a novel molecular target can facilitate CPA-based chemotherapy by selectively promoting its bioactivation.
Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling
Authors: Fulzele Keertik , Krause Daniela S. , Panaroni Cristina , Saini Vaibhav , Barry Kevin J. , Liu Xiaolong , Lotinun Sutada , Baron Roland , Bonewald Lynda , Feng Jian Q. , Chen Min , Weinstein Lee S. , Wu Joy Y. , Kronenberg Henry M. , Scadden David T. , Divieti Pajevic Paola 
Published: November 2012

Key Points
Deletion of Gsα in osteocytes induces severe osteopenia and a dramatic expansion of cells of the myeloid lineage. Osteocytes regulate hematopoiesis and specifically contribute to myelopoiesis by secreting proliferative factors such as G-CSF.