bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participation of the rostral anterior cingulate cortex in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray and contextual fear conditioning
Authors: de Oliveira Galvão Bruno , Filgueiras Alberto , Maisonnette Silvia , Krahe Thomas E. , Landeira-Fernandez J. 
Published: December 2019

AbstractThe rostral anterior cingulate cortex (rACC) is a critical brain structure related to defensive behavior. However, still unclear is whether the rACC also plays a role in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into the dPAG to determine freezing and escape response thresholds after sham or bilateral electrolytic lesions of the rACC. The duration of freezing behavior that outlasted electrical stimulation of the dPAG was also measured. The next day, these animals were subjected to contextual fear conditioning using footshock as an unconditioned stimulus. Lesions of the rACC did not change aversive freezing and escape response thresholds but disrupted post-dPAG stimulation freezing. The lesions also disrupted defensive freezing behavior and analgesia in the formalin test in response to contextual cues previously associated with footshock. These results indicate that the rACC is involved in some but not all aspects of defensive behavior generated at the level of the dPAG. The rACC also appears to play an important role in contextual fear conditioning.
A key regulatory protein for flagellum length control in stable flagella
Authors: Atkins Madison , Týč Jiří , Shafiq Shahaan , Ahmed Manu , Bertiaux Eloïse , De Castro Neto Artur Leonel , Sunter Jack , Bastin Philippe , Dean Samuel , Vaughan Sue 
Published: December 2019

SummaryCilia and flagella are highly conserved microtubule-based organelles that have important roles in cell motility and sensing [1]. They can be highly dynamic and short lived such as primary cilia or Chlamydomonas [2] or very stable and long lived such as those in spermatozoa [3] photoreceptors [4] or the flagella of many protist cells [3,4]. Although there is a wide variation in length between cell types, there is generally a defined length for a given cell type [1]. Many unicellular flagellated and ciliated organisms have an additional challenge as they must maintain flagella/cilia at a defined length whilst also growing new flagella/cilia in the same cell. It is not currently understood how this is achieved. A grow-and-lock model was proposed for the maintenance of stable flagella where a molecular lock is applied to prevent flagellum length change after assembly [5]. The molecular mechanisms of how this lock operates are unknown, but could be important in cells where an existing flagellum must be maintained whilst a new flagellum assembles. Here we show that Cep164C contributes to the locking mechanism at the base of the flagellum in Trypanosoma brucei. It is only localised on the transition fibres of basal bodies of fully assembled flagella and missing from assembling flagella. In fact, basal bodies only acquire Cep164C in the third cell cycle after they assemble in trypanosomes. Depletion leads to dysregulation of flagellum growth with both longer and shorter flagella; consistent with defects in a flagellum locking mechanism. By controlling delivery of components into the old assembled flagellum, maintenance of stable flagella can occur but limits further growth. This offers an important explanation for how many eukaryotic unicellular cells maintain their existing flagella whilst growing new ones before these cells divide. This work also reveals additional regulatory roles for Cep164 in eukaryotic organisms.
Airbnb impact and regulation issues through destination life cycle concept
Authors: Avdimiotis Spyros , Poulaki Ioulia 
Published: December 2019

Purpose
The purpose of this paper is to re-establish the role of Airbnb platform in the contemporary tourism destination management. Given the fact that sharing economy is mega-trend with various impacts at any destination, the paper’s purpose is to underline that sharing economy platforms, such as Airbnb, has a different impact on each stage of destination’s life cycle. Given this, a more effective strategy and policies plan should be deployed and implemented, expanding the benefits of multiplying and accelerating effects on local economy.

Design/methodology/approach
The neologisms of “Over-tourism” and “Tourism-phobia” and the growing conflicts between locals and tourist, along with various collateral implications in local economy, were the initial incentive to focus on the subject. The methodology was based on the critical approach of regulatory measures taken in destinations with different characteristics.

Findings
Findings indicate that general and nationwide restrictions on Airbnb are often unfounded, mainly based on bias against its impact on traditional hotels and local lifestyle preservation, rather than concrete and objective impact measurements.

Research limitations/implications
A primary qualitative and quantitative research should follow the concept of association between destination’s life cycle and sharing economy applications, for authorities to form the appropriate regulatory framework.

Originality/value
The paper associates the implications of sharing economy with the stages of destinations life cycle, underlying that measures need to be customized to the specific characteristics of each destination.
Where are Islamic finance indices pointing towards?
Authors: El Maknouzi Mohammed El Hadi , Jadalhaq Iyad Mohammad 
Published: December 2019

Purpose
This paper aims to survey the screening practices and regulatory arrangements that can be gleaned from the experience of Islamic financial indices on international stock markets. Such indices can be regarded as experiments in the demarcation of “pockets” of Sharī‘ah-compliant securities exchange, in the context of non-Sharī‘ah-compliant stock markets. They offer valuable regulatory precedent, with a view to the development of a transnational domain of Islamic financial transactions.

Design/methodology/approach
The paper leverages the experience of Islamic financial indices for charting the fault lines between the foundational principles of Islamic finance, and those of interest-based investment commonly accepted on international financial markets. It subsequently reviews the most salient regulatory arrangements in place for discriminating between permissible and forbidden securities and modes of trading, as implemented on Islamic financial indices. These include selection criteria for index inclusion, and Sharī‘ah committees with ex ante and ex post supervisory duties.

Findings
The paper makes a case for viewing Islamic finance indices on international capital markets as capacity-building experiments for the regulation of transnational Islamic financial flows.

Originality/value
The study rejuvenates the pragmatic approach towards the development of Islamic capital markets, by suggesting that incremental organisational innovations, as developed in connection with Islamic financial indices, can build institutional capacity towards an economy that abides by Islamic values.
Evaluation of brand relationship quality using formative index: a novel measurement approach
Authors: Adhikari Kishalay , Panda Rajeev Kumar 
Published: December 2019

PurposeThis paper aims to develop a parsimonious and robust formative index for evaluating and measuring the brand relationship quality of automobile brands.Design/methodology/approachSurvey questionnaires were used to collect empirical data from 395 car owners, out of which 362 samples were included in the final analysis. Partial least squares technique was used for index construction.FindingsThe empirical findings exhibit that the automobile brand relationship quality (ABRQ) index based on the final set of six indicators effectively captures the conceptual domain of brand relationship quality. In addition, the external validity check affirms positive and significant influence of ABRQ index toward enhancing customer loyalty.Practical implicationsABRQ index can assist the brand managers and academicians for benchmarking and market strategy formulation while contributing to the limited literature on brand relationship quality. Also, this index having six-indicators can considerably reduce the time and effort of respondents for filling the questionnaires, in turn, improving response rates.Originality/valueThis study represents a novel attempt to formulate a brand relationship quality index using formative measurement indicators, and as per the authors’ knowledge, has not been attempted by prior researchers in this domain.
Coles and Woolworths have installed public access defibrillators in all their stores: It is time other Australian businesses followed their lead
Authors: Haskins Brian , Nehme Ziad , Cameron Peter , Bernard Stephen , Parker‐Stebbing Laura , Smith Karen 
Published: December 2019

AbstractWe welcome the recent announcement by Coles and Woolworths that public access defibrillators (PADs) are now available in their stores, as early defibrillation with PADs is associated with significantly increased survival from out‐of‐hospital cardiac arrests (OHCAs). From 2008 to 2018 there were 120 OHCAs in Victorian supermarkets, overall 26.6% survived; however, when defibrillated by a PAD 66.6% survived. For all OHCA in Victoria, survival for defibrillation by a PAD was also higher at 55.5%, compared to 28.8% for paramedic defibrillation. Using this state‐wide PAD survival rate, we estimate an additional 12 patients could have survived had PADs been available in all supermarkets. In Victoria last year there were 421 potentially viable OHCAs in public locations, of these 132 patients survived; however, had PADs been available an additional 101 patients could have survived. We therefore strongly encourage local businesses to install PADs, to safeguard the well‐being of their employees, customers and local communities.
Immunohistochemistry in screening for heritable colorectal cancer: what to do with an abnormal result
Authors: Paredes Steven R. , Chan Charles , Rickard Matthew J. F. X. 
Published: December 2019

AbstractRecent developments in our understanding of molecular genetics have transformed screening and diagnostic practices for Lynch syndrome. The current standard involves universal tumour analysis of resected colorectal cancer (and ideally polypectomy) specimens using immunohistochemistry and molecular techniques. Patients with abnormal immunohistochemical findings are subsequently referred for definitive mutational testing. This review relates the molecular pathogenesis of Lynch syndrome to current immunohistochemistry‐based screening strategies and discusses the interpretation and clinical implications of screening results.
Potential mechanism of primary resistance to icotinib in patients with advanced non–small cell lung cancer harboring uncommon mutant epidermal growth factor receptor: A multi‐center study
Authors: Lei Lei , Wang Wen‐xian , Zhu You‐cai , Li Jin‐luan , Fang Yong , Wang Hong , Zhuang Wu , Zhang Yin‐bin , Wang Li‐ping , Fang Mei‐yu , Xu Chun‐wei , Wang Xiao‐jia , Lv Tang‐feng , Song Yong 
Published: December 2019

AbstractThe incidence of epidermal growth factor receptor uncommon mutation (EGFRum) is relatively low and patients harboring EGFRum are resistant to the first‐generation tyrosine kinase inhibitors (TKI). However, the mechanism of primary resistance remains unclear. Medical records of 98 patients who had never been treated by TKI and who accepted icotinib treatment were collected and followed. The circulating tumor DNA (ctDNA) were detected and analyzed using the next‐generation sequencing (NGS) platform after progression on icotinib. The potential primary resistance mechanism of icotinib was explored. A total of 21 (21.4%) and 48 (49%) patients developed primary and acquired resistance to icotinib, respectively. The median progression‐free survival (PFS) of primary resistance patients was 1.8 months (0.5‐2.3, 95% CI = 1.50‐2.10). Before treatment, 52.4% (11/21) of patients carried S768I, 23.8% (5/21) L861Q, 14.3% (3/21) G719X and 14.3% (3/21) exon 20‐ins mutations. Approximately 23.8% (5/21) of patients harbored the combined pattern mutations and 76.2% (16/21) of patients harbored the single pattern mutations. The combined pattern with EGFR classical mutation (EGFRcm) had worse PFS than the combined with EGFRum and single pattern (P < .05). There were 6 (28.57%) patients with acquired EGFR extracellular domain mutation, 5 (23.81%) with BCL2L11 loss (BIM deletion polymorphism), 3 (14.29%) with MET amplification, 1 (4.76%) with ERBB2 amplification, 1 (4.76%) with MYC amplification, 1 (4.76%) with PTEN mutation, 1 (4.76%) with PIK3CA mutation and 3 (14.29%) with unknown status. EGFR extracellular domain mutation, BCL2L11 loss, PI3K‐AKT‐mTOR signaling pathway (PTEN and PIK3CA mutations), MET amplification, ERBB2 amplification or MYC amplification might contribute to molecular mechanisms of primary resistance to icotinib in patients with advanced non‐small cell lung cancer harboring uncommon mutant epidermal growth factor receptor. Combined targeted therapy or chemotherapy should be considered in this population.
TIGIT as an emerging immune checkpoint
Authors: Harjunpää H , Guillerey C 
Published: December 2019

SummaryT cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes that was recently propelled under the spotlight as a major emerging target in cancer immunotherapy. TIGIT interacts with CD155 expressed on antigen-presenting cells or tumour cells to down-regulate T cell and natural killer (NK) cell functions. TIGIT has emerged as a key inhibitor of anti-tumour responses that can hinder multiple steps of the cancer immunity cycle. Pre-clinical studies indicated that TIGIT blockade may protect against various solid and haematological cancers. Several monoclonal antibodies (mAbs) that block the inhibitory activity of human TIGIT have been developed. Clinical trials are ongoing, investigating TIGIT blockade as a monotherapy or in combination with anti-PD1/PD-L1 mAbs for the treatment of patients with advanced solid malignancies. In this review, we cover our current knowledge on TIGIT, from its discovery in 2009 to its current status as a clinical target.
Older Australians' perceptions of alcohol‐related harms and low‐risk alcohol guidelines
Authors: Chapman Janine , Harrison Nathan , Kostadinov Victoria , Skinner Natalie , Roche Ann 
Published: December 2019

AbstractIntroduction and AimsAustralia has an ageing population. Given the concomitant increase in the numbers and proportion of risky drinkers among older adults, research examining contributory factors is a priority. The current study examined older adults' estimates of the NHMRC low‐risk drinking guidelines, consumption patterns and associated harms and self‐identification of drinking type.Design and MethodsData from respondents aged 50+ years (N = 11 886) in the 2016 National Drug Strategy Household Survey were subjected to secondary analyses. Estimates of low‐risk drinking levels, perceived level of harm from current drinking, self‐identification of drinking type and awareness of standard drinks and labelling were included. Data were examined for those aged 50–59 years and 60+.ResultsSeventeen percent of older Australians drank at both long‐term and short‐term risk levels. Approximately 39% of males and 11% of females overestimated the long‐term low‐risk levels and 54% of males and 20% of females overestimated the short‐term low‐risk levels. Overestimation was highest among risky drinkers. Most older risky drinkers were aware of standard drinks and labelling; however, less than half perceived their drinking as harmful, instead identifying as social drinkers.Discussion and ConclusionsAlthough substantial gaps are evident in older respondents' estimates of low‐risk drinking, additional public awareness campaigns are likely to be of limited use. Older peoples' engagement with the public health system presents ‘windows of opportunity’ to provide targeted, age‐appropriate harm reduction strategies. Appropriate intervention and policy responses are required to direct resources to this emerging area of concern.
Migrations and movements of Atlantic tarpon revealed by two decades of satellite tagging
Authors: Luo Jiangang , Ault Jerald S. , Ungar Bruce T. , Smith Steven G. , Larkin Michael F. , Davidson Thomas N. , Bryan David R. , Farmer Nicholas A. , Holt Scott A. , Alford A. Scott , Adams Aaron J. , Humston Robert , Marton Adam S. , Mangum David , Kleppinger Russell , Requejo Angel , Robertson Julian 
Published: December 2019

AbstractUnderstanding large‐scale migratory behaviours, local movement patterns and population connectivity are critical to determining the natural processes and anthropogenic stressors that influence population dynamics and for developing effective conservation plans. Atlantic tarpon occur over a broad geographic range in the Atlantic Ocean where they support valuable subsistence, commercial and recreational fisheries. From 2001 through 2018, we deployed 292 satellite telemetry tags on Atlantic tarpon in coastal waters off three continents to document: (a) seasonal migrations and regional population connectivity; (b) freshwater and estuarine habitat utilization; (c) spawning locations; and (d) shark predation across the south‐eastern United States, Gulf of Mexico and northern Caribbean Sea. These results showed that some mature tarpon make long seasonal migrations over thousands of kilometres crossing state and national jurisdictional borders. Others showed more local movements and habitat use. The tag data also revealed potential spawning locations consistent with those inferred in other studies from observations of early life stage tarpon leptocephalus larvae. Our analyses indicated that shark predation mortality on released tarpon is higher than previously estimated, especially at ocean passes, river mouths and inlets to bays. To date, there has been no formal stock assessment of Atlantic tarpon, and regional fishery management plans do not exist. Our findings will provide critical input to these important efforts and assist the multinational community in the development of a stock‐wide management information system to support informed decision‐making for sustaining Atlantic tarpon fisheries.
RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4‐STIL complexes in the nucleus
Authors: Kunimoto Hiroyuki , Inoue Akira , Kojima Hirotada , Yang Junhao , Zhao Hong , Tsuruta Daisuke , Nakajima Koichi 
Published: December 2019

AbstractRNA‐binding motif protein 10 (RBM10) primarily regulates alternative splicing of certain genes. Loss‐of‐function mutations in RBM10 have been frequently reported in patients with various cancers. However, how RBM10 levels affect cell proliferation and tumorigenesis remains unknown. To elucidate the role of RBM10 in cell proliferation, we established HepG2‐RBM10 knockout cell lines and derivative doxycycline‐inducible RBM10‐expressing cells. RBM10 over‐expression caused growth arrest in the M phase with a monopolar spindle because of impaired centriole duplication. Two RBM10 splicing mutants, one with F345A/F347A and the other with only the C‐terminal half (401–930), were sufficient to cause growth arrest, whereas an RBM10 mutant with cytoplasmic localization forced by an NES did not show growth arrest. RBM10 over‐expression induced the formation of many large nuclear domains containing RBM10, PLK4, STIL and SAS6, which are the regulatory proteins involved in centriole duplication. Consistently, the centrioles in the RBM10‐over‐expressing HepG2 cells lost PLK4 and STIL, accounting for the unsuccessful centriole duplication. In contrast, RBM10 depletion resulted in elevated levels of cytoplasmic PLK4 with a concomitant increase in the number of centrioles in HepG2 cells but not in A549 cells. Thus, nuclear RBM10 regulates normal chromosomal division in a cell‐type‐specific manner, independent of alternative RNA splicing.
Inhibitor epidemiology and genetic‐related risk factors in people with haemophilia from Côte d’Ivoire
Authors: Lambert Catherine , Lannoy Nathalie , Meité N’Dogomo , Sanogo Ibrahima , Eeckhoudt Stéphane , Hermans Cedric 
Published: December 2019

AbstractIntroductionIn Sub‐Saharan Africa, inhibitor prevalence data in people with haemophilia (PWH) are scarce, as are data on genetic or treatment‐related risk factors.Aims and methodsWe performed a prospective study on PWH from Côte d’Ivoire to collect data into inhibitor prevalence, create a database of haemophilia genotypes, establish correlations between inhibitor presence and genetic variants identified amongst Ivoirian PWHs and evaluate exposure to CFCs.ResultsThe study included 54 unrelated participants (43 severe, four moderate, two mild haemophilia A and five severe haemophilia B). PWH were treated on‐demand with various product types for short periods, non‐intensively, and using low‐dose regimens. We reported similar distributions of intron 22 inversions (39.5%), point pathogenic variants (32.6%) and rearrangements in Ivoirian severe haemophilia A patients versus non‐African ethnic groups. The haplotypes H1 (29.6%), H2 (36.3%) and H3 (34.1%) frequencies in haemophilia A were consistent with results published on African populations. We identified eight new causal variants. An inhibitor was found in 12% of haemophilia A patients previously exposed to replacement therapies. Among PWH with inhibitors, 66.7% had a positive intron 22 inversion and 50% the H1 haplotype.ConclusionThis study provides original data on molecular diagnosis of haemophilia, inhibitor prevalence and risk factors for inhibitor development previously associated with inhibitors in Côte d’Ivoire. The low inhibitor prevalence likely reflects the limited exposure to replacement therapy in Côte d’Ivoire. Further larger, multicentric and international studies are needed to gain more insight on inhibitor incidence and risk factors in African PWH.
Magnesium‐dependent activated partial thromboplastin time assay—Simple method for lupus anticoagulant detection
Authors: Tokutake Takayoshi , Ieko Masahiro , Naito Sumiyoshi , Yoshida Mika , Baba Hisami , Kobayashi Hikaru , Ishida Fumihiro 
Published: December 2019

AbstractIntroductionDetection of lupus anticoagulant (LA), an antiphospholipid (aPL) antibody, in a clotting time test is an important finding for diagnosis of antiphospholipid syndrome (APS). However, confirmation of LA requires several different testing procedures, some of which can be difficult and require time. We report here a simple and highly specific method for detecting LA.Materials and MethodsWe examined 66 plasma samples obtained from LA‐positive (LA) and 75 from LA‐negative (non‐LA) subjects, which included patients with acquired hemophilia and coagulation disorders, as well as from 43 healthy volunteer samples as normal controls. Activated partial thromboplastin time (APTT) was determined by adding 20 mmol of CaCl2 (Ca‐APTT) or 25 mmol of a mixture of Mg and Ca (Mg‐APTT). The ratio of Mg‐APTT/Ca‐APTT was then calculated and used as the Mg/Ca Index.ResultsThe Mg/Ca Index value for the LA group was significantly lower than that for the non‐LA and normal control groups (P < .0001). When the cutoff value of the Mg/Ca Index was less than 1.00, the sensitivity of LA determination using the Mg‐APTT assay was 80.3%, while specificity was 100%.ConclusionOur findings indicate that the present Mg‐APTT assay is a simple yet highly specific method for LA detection.