bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Small Audit Firm Membership in Associations, Networks, and Alliances Can Impact Audit Quality and Audit Fees
Authors: Bills Kenneth L. , Cunningham Lauren M. 
Published: September 2015

SUMMARY
This article summarizes “Small Audit Firm Membership in Associations, Networks, and Alliances: Implications for Audit Quality and Audit Fees” (Bills, Cunningham, Myers 2015), which examines the association between small audit firm membership in an association, network, or alliance (collectively referred to as an “association”), audit quality, and audit fees. We find that small audit firm association members provide higher-quality audits and charge higher fees than small audit firms that are not members of an association. When compared to similarly sized clients audited by the Big 4, we find that member firms provide audit quality similar to the Big 4 firms, but member firms charge lower fees than their Big 4 counterparts. We caution that these results may not be generalizable to the largest Big 4 clients for which there is not a similarly sized client audited by our sample of small audit firms. We infer audit quality from Public Company Accounting Oversight Board inspections, restatement announcements, and discretionary accruals. Our findings should be of interest to audit committees in charge of auditor selection and to small audit firms interested in the benefits of association membership.
Secretion Rates of Human Nasal Submucosal Glands from Patients with Chronic Rhinosinusitis or Cystic Fibrosis
Authors: Jeong Jin Hyeok , Hwang Peter H. , Cho Do-Yeon , Joo Nam Soo , Wine Jeffrey J. 
Published: September 2015

Background A majority of patients with cystic fibrosis (CF) have chronic rhinosinusitis (CRS) and/or nasal polyps, both of which may be secondary to reduced fluid secretion from nasal submucosal glands. Objective To determine whether decreased fluid secretion from nasal submucosal glands also occurs in patients without CF and with CRS. Methods Inferior turbinates of the nasal cavity were harvested from controls, subjects with CRS, and subjects with CF (n = 5–7 per group). The secretion rates of the nasal submucosal glands of the three groups in response to carbachol and forskolin were measured by using time lapse digital imaging of mucus bubbles from single glands as they formed on the mucosal surface under oil. Results Carbachol-stimulated secretion rates were the following: controls, 1670 ± 381 pl-min−1-gland−1; CRS, 965 ± 440 pl-min−1-gland−1; and CF, 933 ± 588 pl-min−1-gland−1 (p = 0.23, Kruskal-Wallis test). Forskolin-stimulated secretion rates were the following: controls, 229 ± 14 pl-min−1-gland−1; CRS, 154 ± 48 pl-min−1-gland−1; and CF, 22 ± 15 pl-min−1-gland−1 (p = 0.008, Kruskal-Wallis test). The ratio of the average secretion rate induced by forskolin to that induced by carbachol was 13.7% in the controls, and 15.9% in CRS and 2.3% in CF groups. Conclusion The only significant difference in this small study was decreased forskolin-stimulated secretion in subjects with CF relative to the other subjects. However, there was a trend toward reduced carbachol-stimulated secretion rates in subjects with CRS and with and without CF relative to controls. Additional studies are needed to determine if nasal submucosal gland hyposecretion occurs in CRS either as a contributor to or as a consequence of CRS pathogenesis.
Clinical Efficacy of Nasal Steroids on Nonallergic Rhinitis and the Associated Inflammatory Cell Phenotypes
Authors: Kirtsreesakul Virat , Hararuk Kodchakorn , Leelapong Jitanong , Ruttanaphol Suwalee 
Published: September 2015

Background Although good response to nasal steroid therapy has been documented in allergic rhinitis (AR), the efficacy of this treatment in non-AR, and the associated inflammatory cell phenotypes has not been fully investigated. Objective To compare the response to steroids in non-AR versus AR and to assess the impact of inflammatory cell phenotypes on non-AR treatment outcomes. Methods A total of 149 patients with rhinitis were divided into non-AR and AR groups by using the allergy skin-prick test. Based on nasal cytology, the non-AR group was further divided into inflammatory non-AR (INAR) and noninflammatory non-AR (NINAR) groups, and the INAR groups were further subdivided into four phenotypes according to inflammatory cell type: non-AR with eosinophils (NARES), non-AR with mast cells (NARMA), non-AR with neutrophils (NARNE), and NARES and mast cells (NARESMA). All the patients were treated over 28 days with 220 μg of nasal triamcinolone acetonide once daily. Nasal symptom score, peak inspiratory flow index, and nasal mucociliary clearance time (NMCCT) were used to evaluate treatment outcomes. Results The initial screening found 67 patients with non-AR and 82 patients with AR. At 28 days after nasal steroid treatment, all nasal symptom score, peak inspiratory flow indexes, and NMCCTs were significantly improved within each group; however, the non-AR group recorded significantly lower levels of improvement in blocked nose, rhinorrhea, sneezing, nasal itching, peak flows, and NMCCTs than the AR group. The NINAR group overall indicated lower levels of improvement than the INAR group. Among the INAR subgroups, the NARESMA, NARES, and NARMA phenotypes had similar outcome improvements, all better than the NARNE phenotype. Conclusion Although both patients with non-AR and those with AR had good steroid response, the patients with non-AR had less improvement than the patients with AR. Patients with NINAR had the worst treatment outcome among the non-AR phenotypes.
Chloroplast microsatellite markers for Artocarpus (Moraceae) developed from transcriptome sequences
Authors: Gardner Elliot M. , Laricchia Kristen M. , Murphy Matthew , Ragone Diane , Scheffler Brian E. , Simpson Sheron , Williams Evelyn W. , Zerega Nyree J. C. 
Published: September 2015

Premise of the study:Chloroplast microsatellite loci were characterized from transcriptomes of Artocarpus altilis (breadfruit) and A. camansi (breadnut). They were tested in A. odoratissimus (terap) and A. altilis and evaluated in silico for two congeners.Methods and Results:Fifteen simple sequence repeats (SSRs) were identified in chloroplast sequences from four Artocarpus transcriptome assemblies. The markers were evaluated using capillary electrophoresis in A. odoratissimus (105 accessions) and A. altilis (73). They were also evaluated in silico in A. altilis (10), A. camansi (6), and A. altilis × A. mariannensis (7) transcriptomes. All loci were polymorphic in at least one species, with all 15 polymorphic in A. camansi. Per species, average alleles per locus ranged between 2.2 and 2.5. Three loci had evidence of fragment‐length homoplasy.Conclusions:These markers will complement existing nuclear markers by enabling confident identification of maternal and clone lines, which are often important in vegetatively propagated crops such as breadfruit.
T-Cell Phenotype and Function following a First cART Regimen Containing Either a Protease Inhibitor or a Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Late Presenters: Results from a Retrospective, ex vivo Study
Authors: Tincati Camilla , Savoldi Alessia , Cannizzo E Stefania , Bellistrì Giusi M , Termini Roberta , Garau Marzia , Mancusi Daniela , Monforte Antonella d'Arminio , Marchetti Giulia 
Published: September 2015

Background We aimed to comparatively assess darunavir/ ritonavir (DRV/r) and efavirenz (EFV)-based first-line cART regimens in the reconstitution of T-cell phenotype and function in HIV-infected, late presenter subjects. Methods Retrospective, ex vivo study on stored peripheral blood mononuclear cell samples of cART-naive, HIV-infected individuals with CD4+ T-cell counts <50>250/μl upon cART initiation with either DRV/r or EFV as third drugs of standard antiretroviral regimens. CD4+ and CD8+ T-cell maturation (CCR7/CD45RA) and proliferation (Ki67), CD8+ T-cell activation (CD38/HLA-DR) as well as HIV- and cytomegalovirus (CMV)-specific responses (CD4/CD8/IL-2/IFN-γ) were studied by flow cytometry at baseline (T0), T3, T6 and T12 months. Soluble inflammatory markers (IL-6 and sCD14) were measured in plasma at T0 and T12. Wilcoxon and Mann–Whitney tests were used for statistics. Results A total of 19 patients started DRV/r and 15 EFV. Both regimens accounted for suppression of the HIV RNA load (<40 copies/ml), reconstitution of absolute CD4+ T-cells and CD4+/CD8+ T-cell ratio. All study participants displayed a significant decrease of activated HLA-DR+CD38+ CD8+ T-cells at all study time points, yet no differences were found between study groups in T-cell activation and maturation phenotype. From a functional standpoint, only individuals receiving DRV/r displayed transitory recovery of HIV-specific IL-2+IFN-γ- CD4+ T-cells (T3: P=0.006) and IL-2-IFN-γ+ CD8+ T-cells (T3: P=0.032). Conclusions DRV/r- and EFV-based regimens have an equal effect on T-cell phenotype and function in HIV late presenters. A temporary restoration of HIV-specific T-cell immunity early in the course of therapy with DRV/r possibly implies a more effective control over HIV in the first months following a PI/r-based regimen, even at late stage of disease.
EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin
Authors: Kudo Hideo , Wang Zhongzhi , Jinnin Masatoshi , Nakayama Wakana , Inoue Kuniko , Honda Noritoshi , Nakashima Taiji , Kajihara Ikko , Makino Katsunari , Makino Takamitsu , Fukushima Satoshi , Ihn Hironobu 
Published: September 2015

Abstract
IL-12 family cytokines are implicated in the pathogenesis of various autoimmune diseases, but their role in the regulation of extracellular matrix expression and its contribution to the phenotype of systemic sclerosis (SSc) remain to be elucidated. Among the IL-12 family members, IL-35 decreases type I collagen expression in cultured dermal fibroblasts. IL-35 consists of p35 and EBI3 subunits, and EBI3 alone could downregulate the protein and mRNA expression of type I or type III collagen in the presence or absence of TGF-β costimulation. We found that collagen mRNA stability was reduced by EBI3 via the induction of miR-4500. The IL-35 levels in the sera or on the surface of T cells were not altered in SSc patients, while EBI3 expression was decreased in the keratinocytes of the epidermis and regulatory T cells of the dermis in SSc skin compared with normal skin, which may induce collagen synthesis in SSc dermal fibroblasts. We also found that gp130, the EBI3 receptor, was expressed in both normal and SSc fibroblasts. Moreover, we revealed that EBI3 supplementation by injection into the skin improves mice skin fibrosis. Decreased EBI3 in SSc skin may contribute to an increase in collagen accumulation and skin fibrosis. Clarifying the mechanism regulating the extracellular matrix expression by EBI3 in SSc skin may lead to better understanding of this disease and new therapeutic strategies using ointment or microinjection of the subunit.
A Reassessment of IgM Memory Subsets in Humans
Authors: Bagnara Davide , Squillario Margherita , Kipling David , Mora Thierry , Walczak Aleksandra M. , Da Silva Lucie , Weller Sandra , Dunn-Walters Deborah K. , Weill Jean-Claude , Reynaud Claude-Agnès 
Published: September 2015

Abstract
From paired blood and spleen samples from three adult donors, we performed high-throughput VH sequencing of human B cell subsets defined by IgD and CD27 expression: IgD+CD27+ (“marginal zone [MZ]”), IgD−CD27+ (“memory,” including IgM [“IgM-only”], IgG and IgA) and IgD−CD27− cells (“double-negative,” including IgM, IgG, and IgA). A total of 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for VH gene mutation, H-CDR3-length, and VH/JH usage, comparing these different characteristics with all sequences from their subset of origin for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency and lower VH4 and higher JH6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (among MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The “IgM-only” subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor–product relationships with CD27+ switched memory B cells, indicating that they represent germinal center–derived IgM memory B cells and that IgM memory and MZ B cells constitute two distinct entities.
Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow
Authors: Yago Tadayuki , Tsukamoto Hiroki , Liu Zhenghui , Wang Ying , Thompson Linda F. , McEver Rodger P. 
Published: September 2015

Abstract
A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin–dependent slow rolling and chemokine-induced, β2 integrin–dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out,” which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti–β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin–triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases.
Fstl1 Promotes Asthmatic Airway Remodeling by Inducing Oncostatin M
Authors: Miller Marina , Beppu Andrew , Rosenthal Peter , Pham Alexa , Das Sudipta , Karta Maya , Song Dae Jin , Vuong Christine , Doherty Taylor , Croft Michael , Zuraw Bruce , Zhang Xu , Gao Xiang , Aceves Seema , Chouiali Fazila , Hamid Qutayba , Broide David H. 
Published: September 2015

Abstract
Chronic asthma is associated with airway remodeling and decline in lung function. In this article, we show that follistatin-like 1 (Fstl1), a mediator not previously associated with asthma, is highly expressed by macrophages in the lungs of humans with severe asthma. Chronic allergen-challenged Lys-Cretg /Fstl1Δ/Δ mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM), a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, whereas administration of an anti-OSM Ab blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness, all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/OSM pathway may be a novel pathway to inhibit airway remodeling in severe human asthma.
Electroencephalography-based monitors
Authors: Gupta Nidhi , Singh Gyaninder 
Published: September 2015

AbstractAn electroencephalogram (EEG), detects changes and abnormalities in the electrical activity of the brain and thus provides a way to dynamically assess brain function. EEG may be used to diagnose and manage a number of clinical conditions such as epilepsy, convulsive and non-convulsive status epilepticus, encephalitis, barbiturate coma, brain death, etc., EEG provides a large amount of information to the anaesthesiologist for routine clinical practice as depth of anaesthesia monitors and detection of sub-clinical seizures; and also for understanding the complex mechanisms of anaesthesia-induced alteration of consciousness. In the initial years, the routine clinical applicability of EEG was hindered by the complexity of the raw EEG signal. However, with technological advancement, several EEG-derived dimensionless indices have been developed that correlate with the depth of the hypnotic component of anaesthesia and are easy to interpret. Similarly, with the development of quantitative EEG tools, the routine use of continuous EEG is ever expanding in the Intensive Care Units. This review, describe various commonly used EEG-based monitors and their clinical applicability in the field of anaesthesia and critical care.
The Acquisition of Preposition Stranding and Pied Piping in Interrogatives by Arab Jordanian EFL Speakers
Authors: Almahammed Yazan Shaker , Ariff Tun Nur Afizah Zainal , Sidek Harison Hanisa Mohd 
Published: September 2015

<p>The current study aimed primarily at investigating the acquisition of preposition stranding and pied piping by Jordanian EFL speakers. As secondary purposes, the study attempted to supply convincing accounts for the occurrence of preposition stranding and pied piping based on previous literature carried out on this area of language. The study also sought to show any instances of Null preposition phenomenon as acquiring preposition stranding and pied piping. In collecting the data needed for the study, grammaticality judgment and correction task was employed. The task consisted of 21 sentences; 15 of which were incorrect as a result of absence of prepositions and 6 were correct. 355 Jordanian EFL students from ten universities took part in this study. The results of the study indicated that, there were no statistical significant difference between the use of preposition stranding and pied piping among the respondents. More specifically, the respondents produced nearly equal rates of preposition stranding and pied piping. In addition, the results showed that transfer from Arabic is the best possible account for use of pied piping since both Arabic and English permit pied piping in interrogative clauses. In contrast, the frequent emergence of preposition stranding can be justified by salience factor. Lastly, the results revealed a strong evidence for the presence of Null preposition in the language of Jordanian EFL speakers. </p>
Acute‐Phase Proteins
Authors: Raynes John G 
Published: September 2015

AbstractAcute‐phase proteins (APPs) form part of the systemic acute‐phase response which accompanies inflammation. Their primary site of synthesis is the hepatocyte in response to interleukin‐6 and other inflammation‐associated cytokines. Clinically, APPs such as C‐reactive protein provide a useful indicator of the extent of inflammation responding most intensely in severe cases such as sepsis, but showing some response in even mild inflammatory insults or stress. Functions of APPs are still poorly defined but are largely homeostatic and diverse including innate protective immune roles, transport functions, protease inhibition, clotting and metabolic functions. Hepatocytes upregulate secretory pathway networks to allow an increased synthetic activity, although some proteins are actively downregulated. Evidence has mounted to show the importance of APPs for protection of the host.Key ConceptsAcute‐phase proteins are increased in response to inflammatory stimuli within 12–72 h.Functions include direct innate recognition, innate immune response in control of inflammation and immunity, transport of a variety of metabolic and micronutrient factors, enzymes and proteins involved in clotting and thrombosis and so on.Hepatocytes are the main source of acute‐phase proteins.Induction is mainly through transcriptional control through STAT3 and other factors.Concentrations return to normal when inflammation subsides and thus they provide a useful rapidly responding clinical marker of inflammation.Some proteins have increased synthesis to replace that consumed (e.g. complement or clotting components) others are required to fulfil new requirements (e.g. lipocalin‐2).The acute‐phase proteins should be viewed as an important part of the overall systemic response to inflammation (acute‐phase response).
Complement: Classical and Lectin Pathways
Authors: Thielens Nicole M , Gaboriaud Christine , Thiel Steffen 
Published: September 2015

Abstract

The classical and lectin pathways of complement are major recognition systems of innate immunity that are found in mammals and other animal species. By means of several multimolecular proteases, each comprising a recognition protein and a protease component, pathogens and other targets are detected and thereby trigger proteolytic reactions. The classical pathway is initiated by C1, a complex of the recognition molecule C1q and two associated enzymes, C1r and C1s, whereas the lectin pathway is initiated by carbohydrate recognition molecules (mannan‐binding lectin (MBL) or one of the three ficolins or collectin‐LK) in complex with another set of enzymes, MBL‐associated serine proteases (MASPs). Both pathways converge to the formation of C3 convertase, a complex protease that cleaves C3, the central component of the complement system. Proteolytic cleavage of C3 generates a series of fragments and elicits various effector mechanisms, including inflammation and phagocytosis. These mechanisms contribute to the elimination of pathogenic microorganisms and altered host cells from blood and tissues and modulate the adaptive immune response.

Key Concepts

C1q, MBL, CL‐LK and ficolins are pattern‐recognition molecules able to sense motifs on pathogens and altered self‐cells.

C1q is a major sensor of apoptotic cells and regulator of immune tolerance.

Proteolytic cleavage of C3 is pivotal for amplification of the complement response and labelling of the target particles.

Target recognition, proteolysis and complex formation generate conformational changes that underlie complement functioning.

Complement activation and activity are tightly regulated to avoid noxious side‐effects on normal host cells and tissues.