bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some prior considerations about dissonance to understand its reduction: Comment on McGrath (2017)
Authors: Vaidis David C. , Bran Alexandre 
Published: August 2018

AbstractIn a recent contribution to this journal, McGrath (2017) provided an overview of the reduction process of cognitive dissonance theory. To discuss the reduction strategy, she reviewed relevant studies and highlighted the means to reduce dissonance as well as factors that promote their use. In the present paper, we would like to raise some points which have not been considered by McGrath. First, we stress the historical development of the theory that orientated the study of attitude change as the major means of reduction. Second, we raise the issue of the term “dissonance” and the different conceptions about its reduction. Last, on the strength of published data, we insist on resistance to change as a central and essential factor to predict the reduction strategy. We consider that these elements, in addition to McGrath's valuable contribution, provide a comprehensive understanding of the current view of the dissonance reduction process.
The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues
Authors: Savelieff Masha G. , Pappalardo Lucia , Azmanis Panagiotis 
Published: August 2018

AbstractAspergillus fungal infections continue to be a significant cause of morbidity and mortality in birds that can, in part, be attributed to the lack of a diagnostic “gold standard” for Aspergillus infection, and which delays the diagnosis, treatment, and outcome of avian patients. At present, none of the available methods in veterinary care can detect aspergillosis early enough and with the accuracy, precision, and specificity required of an ideal diagnostic tool. Therefore, researching methods of Aspergillus detection is still an active area of inquiry, and novel techniques continue to emerge. This review will provide a brief overview of current clinical methods, with an emphasis on avian care, in addition to a series of techniques in development that could offer distinct advantages over existing methods.
Global reggae and the appropriation of Jamaican Creole
Authors: Gerfer Anika 
Published: August 2018

AbstractThe present study investigates the sociolinguistics of globalisation and performance, focusing on the linguistic appropriation of Jamaican Creole (JC) by white reggae artists in reggae performances and interviews.1By adopting a multi‐faceted approach including a phonetic, morpho‐syntactic, and lexical analysis of the singing and speaking style of seven reggae artists and bands from the USA, Bermuda, and Europe, this study explores the similarities and differences between on‐ and offstage uses of Jamaican Creole, and whether the singers’ access and exposure to this variety as well as the topic of the song has an effect on their language behaviour. The findings provide evidence for the claim that Jamaican Creole has developed into a prestigious linguistic resource in non‐Jamaican artists’ performances of a global reggae persona, both on‐ and offstage.
Passive heat therapy protects against endothelial cell hypoxia‐reoxygenation via effects of elevations in temperature and circulating factors
Authors: Brunt Vienna E. , Wiedenfeld‐Needham Karen , Comrada Lindan N. , Minson Christopher T. 
Published: August 2018

Key Points
Accumulating evidence indicates that passive heat therapy (chronic use of hot tubs or saunas) has widespread physiological benefits, including enhanced resistance against novel stressors (‘stress resistance’).
Using a cell culture model to isolate the key stimuli that are likely to underlie physiological adaptation with heat therapy, we showed that both mild elevations in temperature (to 39°C) and exposure to serum from human subjects who have undergone 8 weeks of heat therapy (i.e. altered circulating factors) independently prevented oxidative and inflammatory stress associated with hypoxia‐reoxygenation in cultured endothelial cells.
Our results elucidate some of the mechanisms (i.e. direct effects of temperature vs. circulating factors) by which heat therapy seems to improve resistance against oxidative and inflammatory stress.
Heat therapy may be a promising intervention for reducing cellular damage following ischaemic events, which has broad implications for patients with cardiovascular diseases and conditions characterized by ‘chronic’ ischaemia (e.g. peripheral artery disease, metabolic diseases, obesity).
AbstractRepeated exposure to passive heat stress (‘heat therapy’) has widespread physiological benefits, including cellular protection against novel stressors. Increased heat shock protein (HSP) expression and upregulation of circulating factors may impart this protection. We tested the isolated abilities of mild heat pretreatment and serum from human subjects (n = 10) who had undergone 8 weeks of heat therapy to protect against cellular stress following hypoxia‐reoxygenation (H/R), a model of ischaemic cardiovascular events. Cultured human umbilical vein endothelial cells were incubated for 24 h at 37°C (control), 39°C (heat pretreatment) or 37°C with 10% serum collected before and after 8 weeks of passive heat therapy (four to five times per week to increase rectal temperature to ≥ 38.5°C for 60 min). Cells were then collected before and after incubation at 1% O2 for 16 h (hypoxia; 37°C), followed by 20% O2 for 4 h (reoxygenation; 37°C) and assessed for markers of cell stress. In control cells, H/R increased nuclear NF‐κB p65 protein (i.e. activation) by 106 ± 38%, increased IL‐6 release by 37 ± 8% and increased superoxide production by 272 ± 45%. Both heat pretreatment and exposure to heat therapy serum prevented H/R‐induced NF‐κB activation and attenuated superoxide production; by contrast, only exposure to serum attenuated IL‐6 release. H/R also decreased cytoplasmic haemeoxygenase‐1 (HO‐1) protein (known to suppress NF‐κB), in control cells (−25 ± 8%), whereas HO‐1 protein increased following H/R in cells pretreated with heat or serum‐exposed, providing a possible mechanism of protection against H/R. These data indicate heat therapy is capable of imparting resistance against inflammatory and oxidative stress via direct heat and humoral factors.
Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts
Authors: Milev Miroslav P , Graziano Claudio , Karall Daniela , Kuper Willemijn F E , Al-Deri Noraldin , Cordelli Duccio Maria , Haack Tobias B , Danhauser Katharina , Iuso Arcangela , Palombo Flavia , Pippucci Tommaso , Prokisch Holger , Saint-Dic Djenann , Seri Marco , Stanga Daniela , Cenacchi Giovanna , van Gassen Koen L I , Zschocke Johannes , Fauth Christine , Mayr Johannes A , Sacher Michael , van Hasselt Peter M 
Published: August 2018

BackgroundThe combination of febrile illness-induced encephalopathy and rhabdomyolysis has thus far only been described in disorders that affect cellular energy status. In the absence of specific metabolic abnormalities, diagnosis can be challenging.ObjectiveThe objective of this study was to identify and characterise pathogenic variants in two individuals from unrelated families, both of whom presented clinically with a similar phenotype that included neurodevelopmental delay, febrile illness-induced encephalopathy and episodes of rhabdomyolysis, followed by developmental arrest, epilepsy and tetraplegia.MethodsWhole exome sequencing was used to identify pathogenic variants in the two individuals. Biochemical and cell biological analyses were performed on fibroblasts from these individuals and a yeast two-hybrid analysis was used to assess protein-protein interactions.ResultsProbands shared a homozygous TRAPPC2L variant (c.109G>T) resulting in a p.Asp37Tyr missense variant. TRAPPC2L is a component of transport protein particle (TRAPP), a group of multisubunit complexes that function in membrane traffic and autophagy. Studies in patient fibroblasts as well as in a yeast system showed that the p.Asp37Tyr protein was present but not functional and resulted in specific membrane trafficking delays. The human missense mutation and the analogous mutation in the yeast homologue Tca17 ablated the interaction between TRAPPC2L and TRAPPC10/Trs130, a component of the TRAPP II complex. Since TRAPP II activates the GTPase RAB11, we examined the activation state of this protein and found increased levels of the active RAB, correlating with changes in its cellular morphology.ConclusionsOur study implicates a RAB11 pathway in the aetiology of the TRAPPC2L disorder and has implications for other TRAPP-related disorders with similar phenotypes.
Homozygosity for the c.428delG variant in KIAA0586 in a healthy individual: implications for molecular testing in patients with Joubert syndrome
Authors: Pauli Silke , Altmüller Janine , Schröder Simone , Ohlenbusch Andreas , Dreha-Kulaczewski Steffi , Bergmann Carsten , Nürnberg Peter , Thiele Holger , Li Yun , Wollnik Bernd , Brockmann Knut 
Published: August 2018

BackgroundJoubert syndrome (JBTS) is a rare neurodevelopmental disorder with marked phenotypic variability and genetic heterogeneity. Homozygous or compound heterozygous mutations in the KIAA0586 gene on chromosome 14q23 are known to be associated with JBTS-23. The frameshift variant c.428delG is the most frequent KIAA0586 variant reported in JBTS-23; yet, homozygosity of this variant was observed in two patients with JBTS-23. However, homozygosity of the c.428delG variant was recently reported as well in one healthy individual.ObjectiveTo clarify whether the frameshift variant c.428delG in KIAA0586 is pathogenic in the homozygous state.MethodsWhole-exome sequencing as well as RNA analysis were performed.ResultsWe identified biallelic mutations, including the variant c.428delG and a splice site variant c.1413–1G>C, in KIAA0586 in two siblings with clinical and MRI features of JBTS. The c.1413–1G>C variant was inherited from the healthy father. The c.428delG variant was found in the healthy mother in a homozygous state in blood lymphocytes, hair root cells and buccal epithelial cells. RNA analysis revealed that the transcript harbouring the c.428delG variant was expressed in blood cells from the healthy mother, indicating that transcripts harbouring this variant elude the mechanism of nonsense-mediated mRNA decay.ConclusionConsidering this and the high allele frequency of 0.003117 in the gnomAD database, we conclude that c.428delG represents a JBTS disease-causing variant only if present in compound heterozygous state with a more severe KIAA0586 variant, but not in a homozygous situation.
Calculations of defect structures and spin Hamiltonian parameters of copper in (70 − x)Bi2O3–xLi2O–30 (ZnO–B2O3) glasses at different compositions
Authors: Zhang Fu , Wu Shao-Yi , Tan Qin-Qin , Zhang Qing , Chen Gui-Jun 
Published: August 2018

Defect structures and spin Hamiltonian parameters (SHPs) and the corresponding composition dependencies are quantitatively analyzed for divalent copper in ([Formula: see text])Bi2O3–[Formula: see text]Li2O–30(ZnO–B2O3) ([Formula: see text] mol.%) glasses by means of the relevant perturbation formulas of an octahedral 3d9 cluster with tetragonal elongation distortion. The [CuO6][Formula: see text] groups are subject to the moderate tetragonal elongation distortions of 4% due to the Jahn–Teller effect. The cubic crystal-field (CF) parameter, orbital reduction factor, tetragonal elongation ratio and core polarization constant exhibit respective piecewise linear functions of Li2O composition [Formula: see text], which suitably account for the experimental optical spectra and the SHPs at various compositions. Mechanisms of these composition dependencies for the related quantities can be explained as the variations of immediate CFs strength and copper–oxygen electron cloud admixtures with increasing Li2O composition.
Abstract A024: Probe Miner: objective, quantitative, data-driven assessment of chemical probes for target validation
Authors: Antolin Albert A. , Tym Joe E. , Komianou Angeliki , Collins Ian , Workman Paul , Al-Lazikani Bissan 
Published: August 2018

Abstract
Chemical probes are important, widely used reagents for understanding biologic systems and for target validation. However, selection of chemical probes is largely subjective and prone to historical and commercial biases. Despite many publications discussing the aspirational properties of chemical probes and the proposal of "fitness factors" to be considered when assessing chemical tools, scientists often select probes through web-based searchers or previous literature that are heavily biased towards older and often flawed probes or use vendor catalogues that do not discriminate between probes. Here, we analyze the scope and quality of published bioactive molecules and uncover large biases and limitations of chemical tools in public databases that need to be urgently addressed and should be always considered when using chemical tools. We also provide the online Probe Miner resource (http://probeminer.icr.ac.uk) capitalizing on the plethora of public pharmacologic data to enable quantitative, unbiased, objective, Big Data-driven assessment of chemical probes and complement expert-curated approaches. We assess &gt;1.8m compounds for their suitability as chemical tools against 2,220 human targets, demonstrating that large-scale public data can contribute to improving chemical probe assessment and prioritization to empower researchers in the selection of chemical tools for biomedical research and target validation.
Citation Format: Albert A. Antolin, Joe E. Tym, Angeliki Komianou, Ian Collins, Paul Workman, Bissan Al-Lazikani. Probe Miner: objective, quantitative, data-driven assessment of chemical probes for target validation [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A024.
Abstract A034: Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: Implications for immunotherapy
Authors: Kim Seung T. , Lim Sung 
Published: August 2018

Abstract
The identification of biomarkers associated with response to therapeutic agents is central to optimizing outcomes. Expression of the immune checkpoint proteins PD-1/L1 and DNA mismatch repair deficiency (dMMR) may be predictive response biomarkers for immunotherapies, but their overlap requires further study. We prospectively conducted PD-L1 and MMR immunohistochemistry (IHC) on 430 consecutive patients with advanced gastrointestinal (GI) cancers, genitourinary (GU) cancers, or rare cancers between June 2012 and March 2016. Correlation between PD-L1 and dMMR was analyzed via t-test and overall survival by the Kaplan-Meier method. Overall, 393/430 (91.4%) patients were evaluable for PD-L1 expression by IHC. The frequency of tumor PD-L1 positivity (PD-L1+) was 16.5% (65/393). Among anatomic tumor sites PD-L1+ was 28.6% in melanoma, 22.2% in GC, 20.9% in CRC, 12.5% in BTC, 7.1% in GU cancer, 6.7% in HCC, 0% in pancreatic cancer, and 0% in sarcoma. Among the 92% evaluable for MLH1/MSH2 expression cases, 18 patients (4.5%) had dMMR tumors. The dMMR was most common in GC (7.1%) followed by 6.7% in HCC, 4.4% in CRC, and 2.7% in sarcoma. Among 365 patients evaluable for both PD-L1 and MLH1/MSH2 expression, there was a significant association between the PD-L1 expression and MLH1/MSH2 loss (P = 0.01), but not with overall survival within tumor types. PD-L1 status and dMMR are overlapping putative reponse biomarkers in immunoncology. Clinical trials with biomarker enrichment for only PD-L1+ or dMMR may be inadequate to completely capture the subset of patients who may benefit. More robust immunotherapy biomarkers and careful clinical trial design are warranted.
Citation Format: Seung T. Kim, Sung Lim. Correlating programmed death ligand 1 (PD-L1) expression, mismatch repair deficiency, and outcomes across tumor types: Implications for immunotherapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A034.
Abstract A041: Gene expression alteration in chronic hypoxic PANC-1 pancreatic cancer cell line
Authors: Zihlif Malek A. , Younis Layaly Hisham Younis Hisham , Sharab Ahmad Sharab 
Published: August 2018

Abstract
Background: Cancer cells grow uncontrollably by disregarding the normal rule of cell division; the resulting overcrowding of cancer cells leads to a decrease in oxygen availability, which is known as hypoxia. The role of tumor hypoxia has become a main focus in cancer research since it is a driving force in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia is a prominent feature of the tumor microenvironment of pancreatic tumors. Objective: The main purpose of this study was to identify the changes in gene expression associated with chronic hypoxia in PANC-1 pancreatic cancer cell line. Methodology: Pancreatic cancer cells (PANC-1) were exposed to 8-hour hypoxic episodes (&lt;1% oxygen) three times a week for a total of 40 episodes. The alterations in gene expression were examined using the real-time based PCR array technology after 20 and 40 episodes of hypoxia and compared to normoxic cells. Chemo-resistance of hypoxic cells toward doxorubicin was assessed using MTT cell proliferation assay. Cell migration was evaluated using wound healing assay. Results: Noticeable gene expression changes were identified after 20 and 40 episodes of hypoxia. No changes were common in both stages, with most genes rebounding at the level of 40 episodes. Notably, genes HIF1AN, HMOX-1, and PKM have been remarkably upregulated by 6.9, 4.5, and 3.4 fold, respectively, after 20 hypoxic shots. The half-maximal inhibitory concentration (IC50) of doxorubicin in PANC-1 cells has increased by approximately 2.7 fold after 20 episodes of hypoxia and increased by approximately 3.6 fold after 40 episodes compared to normoxic cells. Conclusion: This study provided evidence that exposing cells to prolonged periods of hypoxia (weeks) results in different expression changes than those induced by short-term hypoxia (&lt;72 hours). It also approved induction of chemo-resistance by chronic hypoxia. Finally, it proposed HIF1AN, HMOX-1, and PKM as a potential biomarkers for hypoxia in pancreatic cancer and as main players in the cellular response to chronic hypoxia.
Citation Format: Malek A. Zihlif, Layaly Hisham Younis Hisham Younis, Ahmad Sharab Sharab. Gene expression alteration in chronic hypoxic PANC-1 pancreatic cancer cell line [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A041.
Abstract A043: Identification of a patient enrichment strategy supporting development of a potent and selective dual TTK/CLK2 inhibitor CC-671
Authors: Xu Shuichan , Tran Tam , Shi Tao , Jiang Ning , Zhu Dan , Riggs Jennifer R. , Boylan John 
Published: August 2018

Abstract
CC-671 is a potent and selective TTK1 (Mps1) and CLK2 inhibitor. In support of a phase I proof of concept, we used an image-based, multiplex cell assay to evaluate the antiproliferative impact of CC-671 across a broad panel of cancer cell lines representing tumors from various anatomic origins. CC-671 potently and selectively inhibited proliferation and induced apoptosis. Cell lines representing leukemia, lymphoma, colorectal cancer (CRC), head and neck (H&N), and bladder cancers were uniformly sensitive to CC-671 while the cell lines from other tumor types, such as breast and lung cancers, were differentially sensitive to CC-671. Cell cycle analysis using phospho-histone H3 (pHH3) as a mitosis biomarker suggested that CC-671 had cell line-specific mitotic effects. CC-671 accelerated mitotic exit in 120 cell lines while causing mitotic block in 37 cell lines at concentrations &lt; 1 μM. Custom gene expression signatures correlating with sensitivity or resistance were generated. Mapping these signatures to a gene expression database of clinical tumor samples identified additional CC-671 sensitive tumor types including Wilms tumor, superficial bladder cancer, triple-negative, and luminal Btype breast cancer, and several squamous cell carcinomas (lung, esophageal, cervical, H&N).
To identify a breast cancer patient selection profile, the CC-671 antiproliferative activity was assessed in a panel of 49 breast cancer cell lines. CC-671 potently inhibited the growth of breast cancer cell lines with 50% inhibitory concentrations (IC50 values) &lt; 100 nM in 14 lines and &gt; 10 μM in 21 lines. Triple-negative breast cancer (TNBC) cell lines were significantly more sensitive to CC-671 than non-TNBC (ER+/PR+ and/or HER2+) lines. Within TNBC, the mesenchymal (M) and basal-like 1 (BL1) subtypes were more sensitive to CC-671. In addition, TNBC lines with cancer stem cell (CSC)-like properties were also sensitive, indicating a potential role of TTK1 and CLK2 in cancer stem cells. Interestingly, mutations in several genes (phosphatidylinositol-4,5-bisphosphate 3kinase 110 kDa catalytic subunit alpha [PIK3CA], serine/threonine kinase 11 [STK11], and phosphatase and tensin homolog [PTEN]) in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway tend to associate with CC-671 TNBC sensitivity. These mutational correlates are being confirmed in additional TNBC lines.
Citation Format: Shuichan Xu, Tam Tran, Tao Shi, Ning Jiang, Dan Zhu, Jennifer R. Riggs, John Boylan. Identification of a patient enrichment strategy supporting development of a potent and selective dual TTK/CLK2 inhibitor CC-671 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A043.