bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visceral leishmaniasis‐associated nephropathy in hospitalised Brazilian patients: new insights based on kidney injury biomarkers
Authors: Meneses Gdayllon C. , De Francesco Daher Elizabeth , da Silva Junior Geraldo B. , Bezerra Gabriela F. , da Rocha Thaiany P. , de Azevedo Isabella E. P. , Libório Alexandre B. , Martins Alice M. C. 
Published: July 2018

AbstractObjectiveTo evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis.MethodsProspective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase‐associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule‐1 (uKIM‐1) and urinary monocyte chemotactic protein‐1 (uMCP‐1), were quantified by immunoassay (ELISA). Also, interferon‐gamma (INF‐y) and C‐reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity.ResultsVL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN‐y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM‐1 and uMCP‐1. Overall, sNGAL, uKIM‐1 and uMCP‐1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN‐y. Only sNGAL showed an early association with AKI development (OR = 2.78, 95% CI = 1.429–5.428, per each increase of 50 ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC‐ROC = 0.81, 95% CI = 0.69–0.93; cut‐off = 154 ng/ml, sensitivity = 82.6%, specificity = 74.1%, P < 0.001).ConclusionsVisceral leishmaniasis‐associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL‐associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients.
Magnetic measurements of roadside topsoil pollution in an active volcanic region: Mt. Hakusan, Japan
Authors: Kawasaki Kazuo , Fukushi Keisuke , Sakai Hideo 
Published: July 2018

AbstractEnvironmental magnetic applications to topsoil have proved useful for investigating roadside pollution. However, such magnetic monitoring has been avoided in volcanic regions due to the high magnetic content in volcanic ash. Environmental magnetic studies are reported for the volcanically active Mt. Hakusan National Park in Japan. In‐field magnetic susceptibility measurements along the park's major road show higher magnetic susceptibilities in topsoils within 1.5 m from the roadside. However, laboratory mass susceptibility measurements fail to show a similar susceptibility trend to the field measurements. Based on rock magnetic analyses, the major magnetic mineral is pseudosingle‐ to multidomain (MD) magnetite that is both increased in abundance in MD and oxidized magnetite near the roadside, indicating that passing vehicles are evidently the main pollutant source. Therefore, even in an active volcanic region where magnetic susceptibility may not be an efficient tool, detailed magnetic measurements can provide the basis for the discrimination of roadside pollution.
Performance of thermophilic anaerobic sludge digester after alkaline‐assisted thermal disintegration optimization using response surface methodology
Authors: Demir Özlem 
Published: July 2018

AbstractThe Box–Behnken statistical experimental design was used to investigate the effects of operating parameters on thermo‐alkaline disintegration of sludge. The optimum disintegration degree was 77.83% at 90°C, 0.2 mol/L NaOH and 25 min retention time. The coefficient of determination (R2) of 97.68% confirms that the model has a very good fitness with the experimental variables. The effects of a thermo‐alkaline disintegration on the performance of the thermophilic anaerobic digestion of sludge were also investigated. The thermo‐alkaline pretreatment showed an initial solubilization effect and methane production (0.73 (L/Lr.day) increased up to around 54% compared to raw sludge (0.48 L/Lr.day). VS removal in disintegrated digester (65.87%) increased of 13.13% compared to conventional sludge digester (52.74%) at the end of the operation. Similarly, methane contents in the biogas of digester fed with disintegrated sludge (71.14%) increased of 6.44% compared to conventional sludge digester (64.7%).
Evolutionary history of human colitis-associated colorectal cancer
Authors: Baker Ann-Marie , Cross William , Curtius Kit , Al Bakir Ibrahim , Choi Chang-Ho Ryan , Davis Hayley Louise , Temko Daniel , Biswas Sujata , Martinez Pierre , Williams Marc J , Lindsay James O , Feakins Roger , Vega Roser , Hayes Stephen J , Tomlinson Ian P M , McDonald Stuart A C , Moorghen Morgan , Silver Andrew , East James E , Wright Nicholas A , Wang Lai Mun , Rodriguez-Justo Manuel , Jansen Marnix , Hart Ailsa L , Leedham Simon J , Graham Trevor A 
Published: July 2018

ObjectiveIBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing.DesignExome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.Results10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated ‘catastrophic’ CNA increase.ConclusionsEvolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.
Haemodynamic outcomes following aortic valve-in-valve procedure
Authors: Zenses Anne-Sophie , Dahou Abdellaziz , Salaun Erwan , Clavel Marie-Annick , Rodés-Cabau Josep , Ong Géraldine , Guzzetti Ezéquiel , Côté Mélanie , De Larochellière Robert , Paradis Jean-Michel , Doyle Daniel , Mohammadi Siamak , Dumont Éric , Chamandi Chekrallah , Rodriguez-Gabella Tania , Rieu Régis , Pibarot Philippe 
Published: July 2018

Background and objectivesTranscatheter aortic valve-in-valve implantation (ViV) has emerged as a valuable technique to treat failed surgical bioprostheses (BPs) in patients with high risk for redo surgical aortic valve replacement (SAVR). Small BP size (≤21 mm), stenotic pattern of degeneration and pre-existing prosthesis–patient mismatch (PPM) have been associated with worse clinical outcomes after ViV. However, no study has evaluated the actual haemodynamic benefit associated with ViV. This study aims to compare haemodynamic status observed at post-ViV, pre-ViV and early after initial SAVR and to determine the factors associated with worse haemodynamic outcomes following ViV, including the rates of high residual gradient and ‘haemodynamic futility’.MethodsEarly post-SAVR, pre-ViV and post-ViV echocardiographic data of 79 consecutive patients who underwent aortic ViV at our institution were retrospectively analysed. The primary study endpoint was suboptimal valve haemodynamics (SVH) following ViV defined by the Valve Academic Research Consortium 2 as the presence of high residual aortic mean gradient (≥20 mm Hg) and/or at least moderate aortic regurgitation (AR). Haemodynamic futility of ViV was defined as <10 mm Hg decrease in mean aortic gradient and no improvement in AR compared with pre-ViV.ResultsSVH was found in 61% of patients (57% high residual gradient, 4% moderate AR) after ViV versus 24% early after SAVR. Pre-existing PPM and BP mode of failure by stenosis were independently associated with the primary endpoint (OR: 2.87; 95% CI 1.08 to 7.65; p=0.035 and OR: 3.02; 95% CI 1.08 to 8.42; p=0.035, respectively) and with the presence of high residual gradient (OR: 4.38; 95% CI 1.55 to 12.37; p=0.005 and OR: 5.37; 95% CI 1.77 to 16.30; p=0.003, respectively) following ViV. Criteria of ViV haemodynamic futility were met in 7.6% overall and more frequently in patients with pre-existing PPM and stenotic BP (18.5%) compared with other patients (2.0%). ViV restored haemodynamic function to early post-SAVR level in only 34% of patients.ConclusionAlthough ViV was associated with significant haemodynamic improvement compared with pre-ViV in >90% of patients, more than half harboured SVH outcome. Furthermore, only one-third of patients had a restoration of valve haemodynamic function to the early post-SAVR level. Pre-existing PPM and stenosis pattern of BP degeneration were the main factors associated with SVH and haemodynamic futility following ViV. These findings provide strong support for the prevention of PPM at the time of initial SAVR and careful preprocedural patient screening.
Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes
Authors: Rodriguez-Vida Alejo , Perez-Gracia Jose Luis , Bellmunt Joaquim 
Published: July 2018

Abstract
Immune checkpoint inhibitors (ICI) have emerged as a novel therapeutic strategy that achieves significant clinical benefit in several tumor types, including urothelial cancer. Overall, these agents have shown objective response rates of around 20% to 23%, which indicates that a significant proportion of patients do not benefit from immunotherapy when given as monotherapy. Moreover, despite an initial response to therapy and an improvement in the median duration of response compared with chemotherapy, still only half of the patients develop long-term maintained remissions. Active research is ongoing in several fields, aiming to increase the number of patients that benefit from ICI, and this research is largely based on the development of biomarkers for personalized immunotherapy and novel combinations of ICI with other agents. This article will review ongoing efforts to develop combinations of ICI with other therapeutic strategies in patients with urothelial cancer, including chemotherapy, targeted agents, other immunotherapy strategies, and radiotherapy.
PERK Regulates Glioblastoma Sensitivity to ER Stress Although Promoting Radiation Resistance
Authors: Dadey David Y.A. , Kapoor Vaishali , Khudanyan Arpine , Thotala Dinesh , Hallahan Dennis E. 
Published: July 2018

Abstract
The aggressive nature and inherent therapeutic resistance of glioblastoma multiforme (GBM) has rendered the median survival of afflicted patients to 14 months. Therefore, it is imperative to understand the molecular biology of GBM to provide new treatment options to overcome this disease. It has been demonstrated that the protein kinase R–like endoplasmic reticulum kinase (PERK) pathway is an important regulator of the endoplasmic reticulum (ER) stress response. PERK signaling has been observed in other model systems after radiation; however, less is known in the context of GBM, which is frequently treated with radiation-based therapies. To investigate the significance of PERK, we studied activation of the PERK–eIF2α–ATF4 pathway in GBM after ionizing radiation (IR). By inhibiting PERK, it was determined that ionizing radiation (IR)-induced PERK activity led to eIF2α phosphorylation. IR enhanced the prodeath component of PERK signaling in cells treated with Sal003, an inhibitor of phospho-eIF2α phosphatase. Mechanistically, ATF4 mediated the prosurvival activity during the radiation response. The data support the notion that induction of ER stress signaling by radiation contributes to adaptive survival mechanisms during radiotherapy. The data also support a potential role for the PERK/eIF2α/ATF4 axis in modulating cell viability in irradiated GBM.
Implications: The dual function of PERK as a mediator of survival and death may be exploited to enhance the efficacy of radiation therapy.
Visual Overview: http://mcr.aacrjournals.org/content/16/10/1447/F1.large.jpg. Mol Cancer Res; 16(10); 1447–53. ©2018 AACR.
Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF–driven Signaling Axis
Authors: Regan Anderson Tarah M. , Ma Shihong , Perez Kerkvliet Carlos , Peng Yan , Helle Taylor M. , Krutilina Raisa I. , Raj Ganesh V. , Cidlowski John A. , Ostrander Julie H. , Schwertfeger Kathryn L. , Seagroves Tiffany N. , Lange Carol A. 
Published: July 2018

Abstract
The metastatic cascade is a complex process that requires cancer cells to survive despite conditions of high physiologic stress. Previously, cooperation between the glucocorticoid receptor (GR) and hypoxia-inducible factors (HIF) was reported as a point of convergence for host and cellular stress signaling. These studies indicated p38 MAPK-dependent phosphorylation of GR on Ser134 and subsequent p-GR/HIF–dependent induction of breast tumor kinase (PTK6/Brk), as a mediator of aggressive cancer phenotypes. Herein, p-Ser134 GR was quantified in human primary breast tumors (n = 281) and the levels of p-GR were increased in triple-negative breast cancer (TNBC) relative to luminal breast cancer. Brk was robustly induced following exposure of TNBC model systems to chemotherapeutic agents (Taxol or 5-fluorouracil) and growth in suspension [ultra-low attachment (ULA)]. Notably, both Taxol and ULA resulted in upregulation of the Aryl hydrocarbon receptor (AhR), a known mediator of cancer prosurvival phenotypes. Mechanistically, AhR and GR copurified and following chemotherapy and ULA, these factors assembled at the Brk promoter and induced Brk expression in an HIF-dependent manner. Furthermore, Brk expression was upregulated in Taxol-resistant breast cancer (MCF-7) models. Ultimately, Brk was critical for TNBC cell proliferation and survival during Taxol treatment and in the context of ULA as well as for basal cancer cell migration, acquired biological phenotypes that enable cancer cells to successfully complete the metastatic cascade. These studies nominate AhR as a p-GR binding partner and reveal ways to target epigenetic events such as adaptive and stress-induced acquisition of cancer skill sets required for metastatic cancer spread.
Implication: Breast cancer cells enlist intracellular stress response pathways that evade chemotherapy by increasing cancer cell survival and promoting migratory phenotypes. Mol Cancer Res; 16(11); 1761–72. ©2018 AACR.
Re-Evaluation of Total CO<sub>2</sub> Concentration in Apparently Healthy Younger Adults
Authors: Kraut Jeffrey A. , Lew Vivian , Madias Nicolaos E. 
Published: July 2018

The initial assessment of acid-base status is usually based on the measurement of total CO<sub>2</sub> concentration ([TCO<sub>2</sub>]) in venous blood, a surrogate for [HCO<sub>3</sub><sup>–</sup>]. Previously, we posited that the reference limits of serum [TCO<sub>2</sub>] in current use are too wide. Based on studies on the acid-base composition of normal subjects, we suggested that the reference limits of serum [TCO<sub>2</sub>] at sea level be set at 23–30 mEq/L. To validate this proposal, we queried the University of California at Los Angeles (UCLA’s) Integrated Clinical and Research Data Repository, a database containing information on 4.5 million patients seen at UCLA from 2006 to the present. Criteria for inclusion included adults (18–40 years of age), who were free of disorders that could affect acid-base balance, were not taking medications that could affect acid-base balance, and were seen for a routine medical examination or immunization in the outpatient setting. The number of individuals who met the inclusion criteria (52% female and 48% male) was 28,480, with a mean age of 28.9 ± 5.1 years. The mean serum [TCO<sub>2</sub>] level was slightly higher in males than females, 26.6 ± 2.16 mEq/L vs. 25.0 ± 2.11 mEq/L (<i>p</i> &#x3c; 0.05). Ninety-one percent of patient values were within the proposed 23–30 mEq/L range and 61.7% were within the 24–27 mEq/L range. These findings validate our proposal that the reference range of serum [TCO<sub>2</sub>] in venous blood at sea level be narrowed to 23–30 mEq/L. Subjects with serum [TCO<sub>2</sub>] outside this range might require assessment with a venous blood gas to exclude the presence of clinically important acid-base disorders.
Left Ventricular Mass Change After Anthracycline Chemotherapy
Authors: Jordan Jennifer H. , Castellino Sharon M. , Meléndez Giselle C. , Klepin Heidi D. , Ellis Leslie R. , Lamar Zanetta , Vasu Sujethra , Kitzman Dalane W. , Ntim William O. , Brubaker Peter H. , Reichek Nathaniel , D’Agostino Ralph B. , Hundley W. Gregory 
Published: July 2018

Background:
Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment.

Methods and Results:

We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non–Anth-bC (n=15), and in 24 cancer-free controls using paired
t
and χ
2
tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (
P
<0.0001) and LV mass (
P
=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (
P
=0.11–0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (
r
=−0.27;
P
<0.01) but not with LVEF declines (
r
=0.11;
P
=0.45). Moreover, this finding was independent of LVEF changes and body weight.

Conclusions:
Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.
Ecumenical Dialogue as Exchange of Knowledge Systems
Authors: Okpaleke Ikenna Paschal 
Published: July 2018

Abstract
The relationship between theology and the social sciences has often been tenuous, mainly due to methodological differences. However, the relationship between the two is quite evident in such areas as pastoral theology and Christian Education, which combine theology with sociological data. This paper attempts to argue in support of a greater relationship between the two, especially between the areas of ecumenical dialogue and social psychology. It addresses the question: How can ecumenical dialogue be re-thought, in the light of insights from social psychology, in order to give room for progress in ecumenical relations? To do this, the paper borrows insights from social psychology to reappraise the necessity of dialogue and to seek a revision of methodologies for approaching it within theology. It is hoped that such an approach would contribute in advancing ecumenical dialogue at official levels as well as facilitating reception at local levels.
Pragmatic transfer, relevance and procedural meaning in L2
Authors: Ifantidou Elly 
Published: July 2018

Abstract
Pragmatic transfer traces back to Thomas’ (1983, 1984) definition of “pragmatic failure” as a violation of sociolinguistic rules which result in misinterpretation (for a historical overview, see Bou Franch, 2012). As a result, negative transfer has received a great deal of attention for being a cause of miscommunication in L2 and a domain where corrective strategies towards native-like performance were much in need (see Kasper, 1992). In this study, positive transfer is triggered by a cognitive procedure rather than a sociolinguistic skill and is examined in terms of learners’ acquired ability to infer pragmatic meanings in L1 and L2. Using the relevance-theoretic distinction of conceptual-procedural meaning (Wilson, 2011), the study seeks to unveil facilitating effects of L1, L2 and interventions on participants’ ability to interpret newspaper editorials while using procedural expressions as evidence for pragmatic inferences drawn.
Vulnerability and Critical Theory
Authors: Ferrarese Estelle 
Published: July 2018

AbstractInVulnerability and Critical Theory, Estelle Ferrarese identifies contemporary developments on the theme of vulnerability within critical theory while also seeking to reconstruct an idea of vulnerability that enables an articulation of the political and demonstrates how it is socially produced. Philosophies that take vulnerability as a moral object contribute to rendering the political, as the site of a specific power and action, foreign to vulnerability and the notion of recognition offered by critical theory does not correct this deficit. Instead, Ferrarese argues that vulnerability, as susceptibility to a harmful event, is above all a breach of normative expectations. She demonstrates that these expectations are not mental phenomena but are situated between subjects and must even be conceived as institutions. On this basis she argues that the link between the political and vulnerability cannot be reduced to the institutional implementation of moral principles. Rather she seeks to rethink the political by taking vulnerability as the starting point and thereby understands the political as simultaneously referring to the advent of a world, the emergence of a relation, and the appearance of a political subject.