bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulatory effect of fibroblast‐derived prostaglandin E2 on keratinocyte stratification in the skin equivalent
Authors: Arai Koji Y. , Fujioka Atsuko , Okamura Ryoko , Nishiyama Toshio 
Published: September 2014

AbstractEpidermal–dermal interaction plays important roles in physiological events such as wound healing. In this study, we examined a double paracrine mechanism between keratinocytes and fibroblasts through interleukin‐1 (IL‐1) and an IL‐1‐induced inflammatory mediator prostaglandin E2 (PGE2) using the skin equivalent. The epidermal layer of the skin equivalent expressed high levels of IL‐1α mRNA (IL1A mRNA) and relatively low levels of IL‐1β mRNA (IL1B mRNA). IL1A mRNA was not detected in fibroblasts. Fibroblasts also expressed low but not negligible levels of IL1B mRNA only in the presence of keratinocytes. Expression of prostaglandin‐endoperoxide synthase 2 mRNA (PTGS2 mRNA) and production of PGE2 in three‐dimensionally cultured fibroblasts were noticeably stimulated by co‐culture with keratinocytes, whereas PTGS2 mRNA expression in the epidermal layer was very low. In addition, hydroxyprostaglandin dehydrogenase 15‐(NAD) mRNA was highly expressed in keratinocytes but not in fibroblasts, and exogenous IL‐1β stimulated PTGS2 mRNA expression in the dermal equivalent. The thickness of the epidermal layer and the number of MKI67‐positive keratinocytes in the skin equivalent were decreased by treatment with indomethacin, and the decrease recovered when exogenous PGE2 was added. These results indicate that keratinocytes stimulate their own proliferation through a double paracrine mechanism mediated by IL‐1 and PGE2.
Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures
Authors: Fraietta Joseph A. , Mueller Yvonne M. , Lozenski Karissa L. , Ratner Deena , Boesteanu Alina C. , Hancock Aidan S. , Lackman-Smith Carol , Zentner Isaac J. , Chaiken Irwin M. , Chung Suhman , LeGrice Stuart F. J. , Snyder Beth A. , Mankowski Marie K. , Jones Natalie M. , Hope Jennifer L. , Gupta Phalguni , Anderson Sharon H. , Wigdahl Brian , Katsikis Peter D. 
Published: September 2014

ABSTRACT

In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2′ deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application
in vivo
. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1.
NS5A Inhibitors Impair NS5A–Phosphatidylinositol 4-Kinase IIIα Complex Formation and Cause a Decrease of Phosphatidylinositol 4-Phosphate and Cholesterol Levels in Hepatitis C Virus-Associated Membranes
Authors: Reghellin V. , Donnici L. , Fenu S. , Berno V. , Calabrese V. , Pagani M. , Abrignani S. , Peri F. , De Francesco R. , Neddermann P. 
Published: September 2014

ABSTRACT
The hepatitis C virus (HCV) nonstructural (NS) protein 5A is a multifunctional protein that plays a central role in viral replication and assembly. Antiviral agents directly targeting NS5A are currently in clinical development. Although the elucidation of the mechanism of action (MOA) of NS5A inhibitors has been the focus of intensive research, a detailed understanding of how these agents exert their antiviral effect is still lacking. In this study, we observed that the downregulation of NS5A hyperphosphorylation is associated with the actions of NS5A inhibitors belonging to different chemotypes. NS5A is known to recruit the lipid kinase phosphatidylinositol 4-kinase IIIα (PI4KIIIα) to the HCV-induced membranous web in order to generate phosphatidylinositol 4-phosphate (PI4P) at the sites of replication. We demonstrate that treatment with NS5A inhibitors leads to an impairment in the NS5A-PI4KIIIα complex formation that is paralleled by a significant reduction in PI4P and cholesterol levels within the endomembrane structures of HCV-replicating cells. A similar decrease in PI4P and cholesterol levels was also obtained upon treatment with a PI4KIIIα-targeting inhibitor. In addition, both the NS5A and PI4KIIIα classes of inhibitors induced similar subcellular relocalization of the NS5A protein, causing the formation of large cytoplasmic NS5A-containing clusters previously reported to be one of the hallmarks of inhibition of the action of PI4KIIIα. Because of the similarities between the effects induced by treatment with PI4KIIIα or NS5A inhibitors and the observation that agents targeting NS5A impair NS5A-PI4KIIIα complex formation, we speculate that NS5A inhibitors act by interfering with the function of the NS5A-PI4KIIIα complex.
Potential for Reduction of Streptogramin A Resistance Revealed by Structural Analysis of Acetyltransferase VatA
Authors: Stogios Peter J. , Kuhn Misty L. , Evdokimova Elena , Courvalin Patrice , Anderson Wayne F. , Savchenko Alexei 
Published: September 2014

ABSTRACT

Combinations of group A and B streptogramins (i.e., dalfopristin and quinupristin) are “last-resort” antibiotics for the treatment of infections caused by Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant
Enterococcus faecium
. Resistance to streptogramins has arisen via multiple mechanisms, including the deactivation of the group A component by the large family of virginiamycin
O
-acetyltransferase (Vat) enzymes. Despite the structural elucidation performed for the VatD acetyltransferase, which provided a general molecular framework for activity, a detailed characterization of the essential catalytic and antibiotic substrate-binding determinants in Vat enzymes is still lacking. We have determined the crystal structure of
S. aureus
VatA in
apo
, virginiamycin M1- and acetyl-coenzyme A (CoA)-bound forms and provide an extensive mutagenesis and functional analysis of the structural determinants required for catalysis and streptogramin A recognition. Based on an updated genomic survey across the Vat enzyme family, we identified key conserved residues critical for VatA activity that are not part of the
O
-acetylation catalytic apparatus. Exploiting such constraints of the Vat active site may lead to the development of streptogramin A compounds that evade inactivation by Vat enzymes while retaining binding to their ribosomal target.
Microwave-Assisted Synthesis and Characterization of Certain Oximes, Hydrazones, and Olefins Derived fromβ-Keto Sulfones
Authors: Abdel-Aziz Hatem A. , Ghabbour Hazem A. , Bhat Mashooq A. , Fun Hoong-Kun 
Published: September 2014

A new series ofβ-keto sulfone derivatives containing oximes4a–e, hydrazones5a, b, and chalcones7a–dwere prepared using microwave irradiation (MWI) by the reaction ofβ-keto sulfones3with hydroxyl amine, hydrazines, and aromatic aldehydes, respectively. The comparative study between microwave irradiation and conventional syntheses showed that MWI is effective in the synthesis of the title compounds through shortening of the reaction time and improvements in their yields. The structures of the synthesized compounds were established under the basis of their spectral data and X-ray single crystal analysis of compound5a. The crystal of5abelongs to triclinic space groupP-1, witha=5.7735   (2) Å,b=9.3224   (3) Å,c=13.1696   (5) Å,α=76.411   (1)°,β=89.571   (1)°,γ=79.9380   (9)°,Z=2,   V=677.97   (4) Å3,Dc=1.513 Mg m−3,μ=0.44 mm−1,F(000)=320,R=0.026, andwR=0.070for 2690 observed reflections withI>2σ(I).
Perfect ALKemy: Optimizing the Use of ALK-Directed Therapies in Lung Cancer
Authors: Politi Katerina , Gettinger Scott 
Published: September 2014

Abstract
Mutations in ALK are a common mechanism of acquired resistance to small molecule ALK inhibitors in ALK-rearranged lung cancer. Different mutants exhibit differential sensitivity to ALK inhibitors. Matching the mutational profile of the tumor with the appropriate ALK inhibitor is likely to be important to maximize benefit for patients. Clin Cancer Res; 20(22); 5576–8. ©2014 AACR.
Left Ventricular Diameter and Risk Stratification for Sudden Cardiac Death
Authors: Narayanan Kumar , Reinier Kyndaron , Teodorescu Carmen , Uy‐Evanado Audrey , Aleong Ryan , Chugh Harpriya , Nichols Gregory A. , Gunson Karen , London Barry , Jui Jonathan , Chugh Sumeet S. 
Published: September 2014

Background

Left ventricular (
LV
) diameter is routinely measured on the echocardiogram but has not been jointly evaluated with the ejection fraction (
EF
) for risk stratification of sudden cardiac death (
SCD
).

Methods and Results

From a large ongoing community‐based study of
SCD
(The Oregon Sudden Unexpected Death Study; population ≈1 million),
SCD
cases were compared with geographic controls.
LVEF
and
LV
diameter, measured using the
LV
internal dimension in diastole (categorized as
normal, mild, moderate
, or
severe
dilatation using American Society of Echocardiography definitions) were assessed from echocardiograms prior but unrelated to the
SCD
event. Cases (n=418; 69.5±13.8 years), compared with controls (n=329; 67.7±11.9 years), more commonly had severe
LV
dysfunction (
EF
≤35%; 30.5% versus 18.8%;
P
<0.01) and larger
LV
diameter (52.2±10.5 mm versus 49.7±7.9 mm;
P
<0.01). Moderate or severe
LV
dilatation (16.3% versus 8.2%;
P
=0.001) and severe
LV
dilatation (8.1% versus 2.1%;
P
<0.001) were significantly more frequent in cases. In multivariable analysis, severe
LV
dilatation was an independent predictor of
SCD
(odds ratio 2.5 [95%
CI
1.03 to 5.9];
P
=0.04). In addition, subjects with both
EF
≤35% and severe
LV
dilatation had higher odds for
SCD
compared with those with low
EF
only (odds ratio 3.8 [95%
CI
1.5 to 10.2] for both versus 1.7 [95%
CI
1.2 to 2.5] for low
EF
only), suggesting that severe
LV
dilatation additively increased
SCD
risk.

Conclusion

LV
diameter may contribute to risk stratification for
SCD
independent of the
LVEF
. This readily available echocardiographic measure warrants further prospective evaluation.
The distribution of the crested and marbled newt species (Amphibia: Salamandridae: Triturus) – an addition to the New Atlas of Amphibians and Reptiles of Europe
Authors: Wielstra Ben , Sillero Neftalí , Vörös Judit , Arntzen Jan W. 
Published: September 2014

In the recently published New Atlas of Amphibians and Reptiles of Europe (Sillero et al., 2014a), the distribution of the newt genusTrituruswas not resolved at the level of the species. The main reason for this was the lack of high quality distribution data from in and around the parapatric contact zones between species, where interspecific hybridization occurs. We are working extensively onTriturusand the (particularly genetic) data we have accumulated allow us to map the individualTriturusspecies at the appropriate scale. We here provide a database composed of distribution data for the individual species, at generally high resolution, particularly from in and around contact zones. Based on this database we produce maps at the 50 × 50 km UTM grid resolution as used in the new atlas and highlight those grid cells in which more than oneTriturusspecies occurs.
New Thoughts on the Social Forms of Ancient China (from the Zhou to Qing Dynasties)
Authors: Jinguang † Zhang 
Published: September 2014

Abstract
The entire course of ancient Chinese history has centered on state power, which dominated and shaped the basic picture of social history. The key to Chinese state power has been the state ownership of land, and based on this we can divide the social forms of ancient China into four successive periods: the period of yishe 邑社時代 or village societies (Western Zhou Dynasty and the Spring and Autumn Period); the period of official communal system 官社時代 (Warring States Period to Qin Dynasty to the early Han Dynasty); the period of half official communal system 半官社時代 (Han to Tang Dynasty); and the period of state vs. individual peasants 國家個體小農時代 (Song to Qing Dynasty).
The Heavens are High and the Emperor is Near: An Imperial Power System that is Open to the People
Authors: Ge Lei 
Published: September 2014

Abstract
When we say that “the Emperor is near,” we are referring not to his nearness to the officials below him but rather to the people. It has always been an indispensable element of the emperor’s authority that he is able to establish a clear relationship with the populace and allow them to directly feel his presence in their everyday lives—both materially and morally—and even more importantly, feel the emperor’s concern for the people on a regular basis. Fostering the people’s sense of coexistence with the emperor is essential to solidifying the emperor’s position and maintaining the emperor’s almost holy image. The development of the imperial power structure through the Qin and Han Dynasties can thus be seen as the continuous development of the relationship between the emperor and his subjects. The main agents in the imperial society can be defined as the emperor, his officials, and the people; it can not be limited simply to the political dynamics between the emperor and the officials. Through his autocratic rule, the emperor has the ability to build a personal, transcendent connection with the people. Imperial rule is by definition autocratic, but the entire imperial power structure necessarily includes the people and his personal relationship with them. By citing multiple historical examples, we can begin to see how the emperors established such personal relationships with the people and why they were important to his rule.
Gender Differences in Lay Knowledge of Type 2 Diabetes Symptoms Among Community-dwelling Caucasian, Latino, Filipino, and Korean Adults - DiLH Survey
Authors: Fukuoka Yoshimi , Bender Melinda S. , Choi JiWon , Gonzalez Prisila , Arai Shoshana 
Published: September 2014

Purpose The purpose of this study was to explore gender differences in lay knowledge of type 2 diabetes symptoms among community-dwelling Caucasian, Latino, Filipino, and Korean Americans. Design and Methods A cross-sectional survey was administered to a convenience sample of 904 adults (172 Caucasians, 248 Latinos, 234 Koreans, and 250 Filipinos) without diabetes at community events, community clinics, churches, and online in the San Francisco Bay Area and San Diego from August to December 2013. Participants were asked to describe in their own words signs and/or symptoms of diabetes. A multiple logistic regression analysis was performed to examine the association of lay symptom knowledge with gender after controlling for potential confounding factors. Results Overall, the average age of the sample populations was 44 (SD ±16.1) years, 36% were male, and 58% were married. Increased thirst/dry mouth following increased urinary frequency/color/odor and increased fatigue/lethargy/low energy were the most frequently reported signs and symptoms (19.8%, 15.4%, and 13.6%, respectively). After controlling for known confounding factors, women were 1.6 (95% confidence interval, 1.2-2.3, P = .004) times more likely than men to report at least 1 diabetes symptom. However, this gender difference in knowledge of diabetes signs and symptoms did not significantly differ across Caucasians, Latinos, Filipinos, and Korean Americans ( P = .87). Conclusion The findings underscore the importance of improving public knowledge and awareness of signs and symptoms of diabetes, particularly in men.
Idiopathic intracranial hypertension: Clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study
Authors: Yri Hanne M , Jensen Rigmor H 
Published: September 2014

Aims The aims of this article are to characterize the headache in idiopathic intracranial hypertension (IIH) and to field-test the ICHD diagnostic criteria for headache attributed to IIH. Materials and methods We included 44 patients with new-onset IIH. Thirty-four patients with suspected but unconfirmed IIH served as controls. Headache and other IIH-related symptoms were assessed by a detailed standardized interview. In participants referred before diagnostic lumbar puncture ( n = 67), we recorded headache intensity before and after cerebrospinal fluid (CSF) withdrawal. Results Headache in patients with IIH was daily occurring in 86%, focal in 84% and pulsating in 52%. Aggravation of headache by coughing or straining and relief after CSF withdrawal were significantly more frequent in patients than in controls ( p ≤ 0.002). From the ICHD-2 to the ICHD-3 beta classification the sensitivity increased from 60% to 86% whereas the specificity decreased from 86% to 53%. Based on our data the headache criteria can be revised to increase sensitivity to 95% and specificity to 65%. Conclusion Aggravation of headache by coughing or straining, relief after CSF withdrawal, retrobulbar pain and pulsatile tinnitus may suggest intracranial hypertension. Based on data from a well-defined IIH cohort, we propose a revision of the ICDH-3 beta diagnostic criteria with improved clinical applicability and increased sensitivity and specificity.
Chronic Statin Use and Long-Term Rates of Sepsis
Authors: Wang Henry E. , Griffin Russell , Shapiro Nathan I. , Howard George , Safford Monika M. 
Published: September 2014

Purpose: “Statins” have immunomodulatory and anti-inflammatory effects and may attenuate the risk of infections. We sought to determine the association between chronic statin use and long-term rates of sepsis events. Materials and Methods: We used data from 30 183 adult (≥45 years old) community-dwelling participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was statin use. The primary outcome was hospitalization or emergency department treatment for sepsis. Using Cox proportional hazards models, we determined associations between statin use and first sepsis events, adjusting for patients demographics, health behaviors, chronic medical conditions, degree of medication adherence, baseline high-sensitivity C-reactive protein (hsCRP), and propensity for statin use. Results: Approximately one-third of participants reported statin use (n = 9475, 31.4%). During the 10-year follow-up period from 2003 to 2012, there were 1500 incident sepsis events. Statin use was not associated with rates of sepsis after multivariable adjustment for demographics, health behaviors, chronic medical conditions, medication adherence, abnormal hsCRP, and propensity for statin use, hazard ratio 0.93 (95% confidence interval: 0.81-1.06). Statin use was not similarly associated with rates of sepsis when stratified by propensity for statin use or medication adherence. Conclusion: In the REGARDS cohort, statin use at baseline was not associated with rates of future sepsis events.
Arthroscopic Treatment of Talus Osteochondral Lesions With Particulated Juvenile Allograft Cartilage
Authors: Giza Eric , Delman Connor , Coetzee J. Chris , Schon Lew C. 
Published: September 2014

Osteochondral lesions of the talus (OLT) are commonly associated with traumatic injury to the ankle joint. Treatment options depend on the grade, location, and size of the lesion. Operative intervention is frequently required with initial management involving marrow stimulation techniques, such as microfracture/curettage. Larger lesions often require a secondary procedure, such as osteochondral transplantation or autologous chondrocyte implantation. The advent of particulated juvenile articular cartilage (PJAC) provides an alternative method for OLTs refractory to traditional treatments. This article describes the technique of PJAC transplantation for the treatment of osteochondral lesions of the talus. Level of Evidence: Level V, expert opinion.
A review of the evidence for occupational exposure risks to novel anticancer agents – A focus on monoclonal antibodies
Authors: King Julie , Alexander Marliese , Byrne Jenny , MacMillan Kent , Mollo Adele , Kirsa Sue , Green Michael 
Published: September 2014

Introduction Evidence of occupational exposure risks to novel anticancer agents is limited and yet to be formally evaluated from the Australian healthcare perspective. Methods From March to September 2013 medical databases, organizational policies, drug monographs, and the World Wide Web were searched for evidence relating to occupational exposure to monoclonal antibodies, fusion proteins, gene therapies, and other unclassified novel anticancer agents. Results Australian legislation, national and international guidelines, and drug company information excluded novel agents or provided inconsistent risk assessments and safe handling recommendations. Monoclonal antibody guidelines reported conflicting information and were often divergent with available evidence and pharmacologic rationale demonstrating minimal internalisation ability and occupational exposure risk. Despite similar physiochemical, pharmacologic, and internalisation properties to monoclonal antibodies, fusion proteins were included in only a minority of guidelines. Clinical directives for the safe handling of gene therapies and live vaccines were limited, where available focusing on prevention against exposure and cross-contamination. Although mechanistically different, novel small molecule agents (proteasome inhibitors), possess similar physiochemical and internalisation properties to traditional cytotoxic agents warranting cytotoxic classification and handling. Conclusion Novel agents are rapidly emerging into clinical practice, and healthcare personnel have few resources to evaluate risk and provide safety recommendations. Novel agents possess differing physical, molecular and pharmacological profiles compared to traditional cytotoxic anticancer agents. Evaluation of occupational exposure risk should consider both toxicity and internalisation. Evidence-based guidance able to direct safe handling practices for novel anticancer agents across a variety of clinical settings is urgently required.
Construction of the ‘other’ in social workers’ discourses of asylum seekers
Authors: Masocha Shepard 
Published: September 2014

Summary This article analyses how asylum seekers are constructed as an out-group in some of the narratives provided by practitioners who were interviewed as part of a wider research study of social workers’ discourses of asylum seekers. Findings Using discursive psychology, the article identifies interpretative repertoires that were used by social workers in their formulations of asylum seekers as the other. The article explores the linguistic resources that were deployed in these formulations. Applications The article highlights the potential contributions of discursive perspectives to social work research, teaching and practice as it illuminates the pivotal role that language plays within the profession in the construction of subjectivities, and specifically in relation to the protection, perpetuation and normalisation of discrimination.