bluuebunny/crossref_metadata_2025 huggingface dataset:
Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms
Authors: Afzali Farzaneh , Salimi Mahdieh
Published: March 2019

Circular RNAs (circRNAs) along other complementary regulatory elements in ceRNAs networks possess valuable characteristics for both diagnosis and treatment of several human cancers including breast cancer (BC). In this study, we combined several systems biology tools and approaches to identify influential BC circRNAs, RNA binding proteins (RBPs), miRNAs, and related mRNAs to study and decipher the BC triggering biological processes and pathways.

Rooting from the identified total of 25 co-differentially expressed circRNAs (DECs) between triple negative (TN) and luminal A subtypes of BC from microarray analysis, five hub DECs (hsa_circ_0003227, hsa_circ_0001955, hsa_circ_0020080, hsa_circ_0001666, and hsa_circ_0065173) and top eleven RBPs (AGO1, AGO2, EIF4A3, FMRP, HuR (ELAVL1), IGF2BP1, IGF2BP2, IGF2BP3, EWSR1, FUS, and PTB) were explored to form the upper stream regulatory elements. All the hub circRNAs were regarded as super sponge having multiple miRNA response elements (MREs) for numerous miRNAs. Then four leading miRNAs (hsa-miR-149, hsa-miR-182, hsa-miR-383, and hsa-miR-873) accountable for BC progression were also introduced from merging several ceRNAs networks. The predicted 7- and 8-mer MREs matches between hub circRNAs and leading miRNAs ensured their enduring regulatory capability. The mined downstream mRNAs of the circRNAs-miRNAs network then were presented to STRING database to form the PPI network and deciphering the issue from another point of view. The BC interconnected enriched pathways and processes guarantee the merits of the ceRNAs networks’ members as targetable therapeutic elements.

This study suggested extensive panels of novel covering therapeutic targets that are in charge of BC progression in every aspect, hence their impressive role cannot be excluded and needs deeper empirical laboratory designs.
Wnt7a-releasing synthetic hydrogel enhances local skeletal muscle regeneration and muscle stem cell engraftment
Authors: Han Woojin M. , Mohiuddin Mahir , Anderson Shannon E. , García Andrés J. , Jang Young C.
Published: March 2019

Skeletal muscle possesses efficient ability to regenerate upon minor injuries, but its capacity to regenerate is severely compromised with traumatic injuries and muscle-associated diseases. Recent evidence suggests that skeletal muscle regeneration can be accelerated by transplantation of muscle satellite cells (MuSCs) or treatment with promyogenic factors, such as Wingless-type MMTV Integrated 7a (Wnt7a) protein. Although direct intramuscular injection is the simplest method to deliver MuSCs and Wnt7a for regenerative therapy, direct injection is not viable in many clinical cases where the structural integrity is severely compromised. To address this challenge, we engineered a synthetic poly(ethylene glycol) (PEG)-based hydrogel to facilitate the co-delivery of pro-myogenic factors, such as Wnt7a, and MuSCs to skeletal muscles affected by severe trauma or muscular dystrophies. Wnt7a release rate can be controlled by modulating the polymer density of the hydrogel, and this release rate can be further accelerated through the proteolytic degradation of the hydrogel. Treating cryo-injured tibialis anterior (TA) muscles with Wnt7a-loaded hydrogels resulted in an accelerated regenerative response, measured by increased muscle fiber cross-sectional area, bulk TA mass, and number of Pax7+MuSCs at the injury site, compared to the TA muscles treated with Wnt7a-free hydrogels. Co-delivery of Wnt7a and primary MuSCs using the synthetic hydrogel to the cryo-injured TA muscles significantly increased cellular migration during the engraftment process. This work provides a synthetic biomaterial platform for advancing treatment strategies of skeletal muscle trauma and diseases, specifically in conditions where direct intramuscular injection may be challenging.
A Modification of the Bielschowsky Silver Stain for Alzheimer Neuritic Plaques: Suppression of Artifactual Staining by Pretreatment with Oxidizing Agents
Authors: Intorcia Anthony J. , Filon Jessica R. , Hoffman Brittany , Serrano Geidy E. , Sue Lucia I. , Beach Thomas G.
Published: March 2019

The Bielschowsky silver method has been the most commonly-used histological stain for demonstrating the neuritic plaques and neurofibrillary tangles that define Alzheimer’s disease (AD). The stain has been critical to providing a common measure allowing large clinicopathological correlation studies that have demonstrated statistically significant and independent contributions of both lesion types to cognitive impairment and dementia. The continuing relevance of neuritic plaques, and the Bielschowsky stain as the method of choice for their demonstration, is also indicated by its use as the US Food and Drug Administration (FDA) “standard of truth” for autopsy confirmation of the validity of PET amyloid imaging agents. Many modifications of the Bielschowsky stain have been published but it is still known to frequently generate artifactual staining that at times mimics the appearance of amyloid plaques. In this study we found that pretreatment with oxidizing agents prior to the initial incubation in silver nitrate eliminates these artifacts and reduces the commonly observed high background staining. This new method may be valuable for Alzheimer’s disease (AD) researchers and neuropathologists.
A homozygous genome-edited Sept2-EGFP fibroblast cell line
Authors: Banko Monika , Mucha-Kruczynska Iwona , Weise Christoph , Heyd Florian , Ewers Helge
Published: March 2019

Septins are a conserved, essential family of GTPases that interact with actin, microtubules and membranes and form scaffolds and diffusion barriers in cells. Several of the 13 known mammalian septins assemble into nonpolar, multimeric complexes that can further polymerize into filamentous structures. While some GFP-coupled septins have been described, overexpression of GFP-tagged septins often leads to artifacts in localization and function. To overcome this ubiquitous problem, we have here generated a genome-edited rat fibroblast cell line expressing Septin 2 (Sept2) coupled to enhanced green fluorescent protein (EGFP) from both chromosomal loci.

We characterize these cells by genomic polymerase chain reaction (PCR) for genomic integration, by western blot and reverse transcriptase-PCR for expression, by immunofluorescence and immunoprecipitation for the colocalization of septins with one another and cellular structures and for complex formation of different septins. By live cell imaging, proliferation and migration assays we investigate proper function of septins in these cells.

We find that EGFP is incorporated into both chromosomal loci and only EGFP-coupled Sept2 is expressed in homozygous cells. We find that endogenous Sept2-EGFP exhibits expression levels, localization and incorporation into cellular septin complexes similar to the wt in these cells. The expression level of other septins is not perturbed and cell division and cell migration proceed normally. We expect our cell line to be a useful tool for the cell biology of septins, especially for quantitative biology.
Effect of organisational integrity and leadership behaviour on organisational excellence
Authors: AL-Abrrow Hadi , Abdullah Hasan , Atshan Nadia
Published: March 2019

Purpose

The purpose of this paper is to study the effect of organisational integrity and leadership behaviour on organisational excellence by considering the mediating role of work engagement in the banking sector.

Design/methodology/approach

The quantitative (questionnaire survey) design was used to gather data from 285 employees of the banking sector in Southern and Central Iraq.

Findings

The findings revealed a partial mediation role of work engagement in the relation between organisational integrity and organisational excellence and a full mediation role between leadership behaviour and organisational excellence.

Research limitations/implications

Managers need to understand that the impact of their leadership behaviour on organisational outcomes; they also have to understand how people think and what motivates them positively. Therefore, managers must deal with employees as internal customers and realise that their satisfaction and performance is the satisfaction of external customers.

Originality/value

Few studies have dealt with this topic in the in developing countries such as Iraq. The increases the strength of competition in the Iraqi banking sector pays more attention to the search for excellence. Therefore, more research efforts are needed for achieving organisational excellence in this sector.
CFTC amends chief compliance officer duties and annual report requirements
Authors: Hammar Julian E.
Published: March 2019

Purpose

This paper summarizes the requirements of rule amendments promulgated by the Commodity Futures Trading Commission (CFTC) in 2018 regarding the duties of Chief Compliance Officers (CCOs) of swap dealers, major swap participants, and futures commission merchants (collectively, Registrants) and the requirements for preparing, certifying and furnishing to the CFTC the CCO’s annual report.

Design/methodology/approach

This paper provides a close analysis of the CFTC’s final rule amendments that make clarifications regarding the CCO’s duties and seek to harmonize with similar rules of the Securities and Exchange Commission (SEC) applicable to security-based swap dealers.It also analyzes rule amendments for the CCO’s report that provide clarifications and simplify certain requirements.In each case, it discusses comments from the public and the CFTC’s responses to those comments.

Findings

This paper finds that the rule amendments provide a number of helpful clarifications and simplify certain existing requirements for Registrants and their CCOs subject to the rules.While the rules overall achieve greater harmonization with similar rules of the SEC governing CCOs of security-based swap dealers, this paper notes that care will need to be taken by CFTC Registrants who also become registered with the SEC to be cognizant of remaining differences between the CFTC’s and SEC’s rules in order to ensure compliance with the rules of each agency.

Originality/value

This paper provides valuable information regarding the duties of CCOs of Registrants and CCO annual report requirements from an experienced lawyer focused on commodities, futures, derivatives, energy, corporate, and securities regulatory matters.
Global environmental policies with innovation spillovers
Authors: Kumar Manoj
Published: March 2019

Purpose

The purpose of this paper is to explore automobile fuel efficiency policies in the presence of two externalities: a global environmental problem and international innovation spillovers.

Design/methodology/approach

Using a simple model with two regions, the authors show that both a fuel tax and a tax on vehicles based on their fuel economy rating are needed to decentralize the first best.

Findings

If standards are used instead of taxes, the authors find that spillovers may alleviate free-riding. Under some conditions, a strict standard in one region may favor the adoption of a strict standard in the other one.

Originality/value

The authors also show that if policies are not coordinated between regions, the resulting gas taxes will be set too low and each region will use the tax on fuel rating to reduce the damage caused by foreign drivers.
The internationalisation of service-sector SMEs in an emerging market
Authors: Ooi Shir May , Richardson Christopher
Published: March 2019

Purpose

This paper aims to explore the internationalisation of service-sector small- and medium-sized enterprises (SMEs) from an emerging market, focussing on the entry modes, psychic distance, business network, internationalisation challenges and capabilities of business training and consultancy firms from Malaysia.

Design/methodology/approach

A multiple-case study approach is adopted, and 31 in-depth interviews were conducted with the top management and executives from eight business training and consultation (BT&C) firms in Malaysia. The Uppsala model is used for theoretical guidance to analyse the internationalisation of the firms.

Findings

The results suggest that psychic distance, business network and business capabilities influence the internationalisation of BT&C firms from Malaysia. However, the discussion of entry modes in the framework of service internationalisation does not accurately explain the internationalisation of the studied firms.

Research limitations/implications

This study is a qualitative research based on the experiences of eight firms. The basis of this study is inadequate for scientific generalisation. Quantitative research should be conducted in the future to provide a statistical test and empirical results. This study is concerned with the emerging-market context. The study could be expanded to include more industries and other emerging markets in the future.

Practical implications

This study explored the application of internationalisation theories to the BT&C industry in an emerging market, with particular emphasis on firms’ entry modes, psychic distance, business networks, international challenges and capabilities. This study also highlighted some of the key internationalisation challenges facing emerging market small- and medium-sized enterprises (EMSMEs), underlining the importance of business networks and capabilities.

Social implications

Nevertheless, this study shares useful and practical discoveries concerning the internationalisation process of BT&C firms from the emerging market, focussing on entry modes, psychic distance, business network, the challenges faced and the required capabilities.

Originality/value

The study provides new insights into service internationalisation in SMEs from an emerging market. The application of internationalisation theories to the BT&C industry in an emerging market is analysed.
The monistic diversity of continuum informatics
Authors: Upward Frank
Published: March 2019

Purpose

The Information Age during the transition from the paper era to the digital one saw the fracturing and fragmenting of the information-based specialisations. More recently, professional norms for governance have been swept aside within new business models based on information based business applications. This paper aims to support an advance towards networked cohesion based on informatics, regenerating professionalism for the complex networked age.

Design/methodology/approach

New regulatory approaches will have to manage monistic diversity, connecting the deeper logic of continuum thinking in which information governance exists as part of a simple whole (the monistic component) with a recognition that the parts of information governance are much more complex than the whole (the expanding diversity). A continuum approach of this type involves studying things in motion as part of evolutionary processes.

Findings

The production of information is galloping ahead of its authoritative management, and this is at the heart of many of the failings of the post-truth information era. Informatics with its emphasis upon the joint operation of technologies, social processes and knowledge forming and its ability to be an umbrella term for many specialisations can be a cohering force.

Practical implications

The alignment of thought, action and ethical information governance across inter-connected practices for individuals, groups and organisations can be supported by the deeper logic and grounded experience of continuum thinking.

Originality/value

This paper will look to expand the array of sympathisers who wish to get more in touch with studying things in motion, including those trying to cope with the need to develop more adequate ways for managing nanosecond archiving processes.
Impostor phenomenon in STEM: occurrence, attribution, and identity
Authors: Chakraverty Devasmita
Published: March 2019

Purpose

This study aims to explore different themes related to impostor phenomenon, as experienced by graduate students and postdocs in science, technology, engineering and mathematics (STEM) fields.

Design/methodology/approach

Open-ended survey responses from 120 US-based participants from 40 states and Washington, D.C., describing an occasion when they felt like an impostor, were analyzed thematically.

Findings

Following content analysis, three themes emerged: occurrence, attribution and identity. While impostor-like feelings were experienced as early as high school or college, the majority experienced it during PhD application, on being admitted to a PhD program and throughout PhD training. The people experiencing impostor phenomenon attributed their achievements and success to others (other’s name, prestige, or connections, other’s mistake, other’s lies or misrepresentation, or other’s kindness) or self (self-inadequacy, pretense, luck or self-doubt) rather than their own hard work or ability. Gender-based and race/ethnicity-based identity also shaped the experiences of the impostor phenomenon.

Research limitations/implications

Open-ended survey responses varied in length and level of detail. Responses provided a one-time snapshot of a memory related to impostor-feelings that stood out, not indicating if the feeling persisted or evolved with time. The findings are not generalizable over a larger population.

Originality/value

This study identified multiple themes related to the impostor phenomenon not investigated before, enriching existing research while also providing methodological rigor for the development of follow-up studies.
Use of trichoscopy for the diagnosis of alopecia areata coexisting with primary scarring alopecia in a female hair loss patient
Authors: Fukuyama Masahiro , Ohyama Manabu
Published: March 2019

Despite patchy hair loss being typically observed in alopecia areata (AA), similar lesions can be seen in other forms of alopecia and the diagnosis is sometimes challenging. Of note, patchy primary scarring alopecia (SA) needs to be clearly distinguished from AA as SA can leave permanent hair loss. Herein, we report a previously unreported case of AA coexisting with SA successfully diagnosed by detailed trichoscopic investigation. A 42‐year‐old woman visited us with patchy hair loss lesions on the scalp. On physical examination, alopecic lesions sized up to 2 cm in diameter were observed in the right temporal and parietal regions. A gentle hair pull test collected dystrophic anagen hairs from some patches. Trichoscopy detected tapering hairs and black dots. The diagnosis of AA was made. However, some reddish patches were totally hair pull test negative, urging us to further evaluate the remaining lesions. Additional trichoscopic investigation revealed the disappearance of follicular ostia and the presence of a white and milky‐red area and peripilar scales, suggestive of SA. In histology, the clinically AA lesion showed peribulbar cell infiltration, while the potentially SA lesion demonstrated inflammatory cell infiltration around the isthmus and the decrease in hair follicles, some of which were replaced by fibrotic tissue. The final diagnosis of AA coexisting with SA was made. Intralesional corticosteroid injection improved AA but not SA. These findings emphasize the need for thorough trichoscopic examination for accurate diagnoses of rare hair loss conditions.
Linearized amplitude variation with offset and azimuth and anisotropic poroelasticity
Authors: Pan Xinpeng , Zhang Guangzhi , Yin Xingyao
Published: March 2019

The normal‐to‐shear weakness ratio is commonly used as a fracture fluid indicator, but it depends not only on the fluid types but also on the fracture intensity and internal architecture. Amplitude variation with offset and azimuth is commonly used to perform the fluid identification and fracture characterization in fractured porous rocks. We demonstrate a direct inversion approach to utilize the observable azimuthal data to estimate the decoupled fluid (fluid/porosity term) and fracture (normal and shear weaknesses) parameters instead of the calculation of normal‐to‐shear weakness ratio to help reduce the uncertainties in fracture characterization and fluid identification of a gas‐saturated porous medium permeated by a single set of parallel vertical fractures. Based on the anisotropic poroelasticity and perturbation theory, we first derive a linearized amplitude versus offset and azimuth approximation using the scattering function to decouple the fluid indicator and fracture parameters. Incorporating Bayes formula and convolution theory, we propose a feasible direct inversion approach in a Bayesian framework to obtain the direct estimations of model parameters, in which Cauchy and Gaussian distribution are used for the a priori information of model parameters and the likelihood function, respectively. We finally use the non‐linear iteratively reweighted least squares to solve the maximum a posteriori solutions of model parameters. The synthetic examples containing a moderate noise demonstrate the feasibility of the proposed approach, and the real data illustrates the stabilities of estimated fluid indicator and dry fracture parameters in gas‐saturated fractured porous rocks.
Physician age and the abandonment of episiotomy
Authors: Howard David H. , Hockenberry Jason
Published: March 2019

Objective

To determine whether women treated by older physicians are more likely to undergo episiotomy.

Data Sources/Study Setting

Hospital discharge data from Pennsylvania for the period 1994 to 2010.

Study Design

We examined the impact of the year in which physicians started delivering babies (a proxy for age) in Pennsylvania on episiotomy rates using a linear probability model with hospital fixed effects.

Data Collection/Extraction Methods

Using diagnosis and procedure codes, we identified women delivering vaginally (N = 1 658 327) and determined the proportion who had an episiotomy.

Principal Findings

The average physician‐level episiotomy rate declined from 54 percent in 1994 to 13 percent in 2010. Rates declined among older and younger physicians, but, at any point in time, women treated by older physicians were more likely to have an episiotomy. A 10‐year difference in physician age is associated with a 6 percentage point increase in episiotomy rates.

Conclusions

Results indicate that older physicians, who entered practice when episiotomy was common, were slow to adjust their practices in response to evidence showing that routine episiotomy is unnecessary.
Frequent fires do not affect sexual expression and reproduction in Vachellia caven
Authors: Marquez Victoria , Carbone Lucas M. , Aguilar Ramiro , Ashworth Lorena
Published: March 2019

In environments with high fire frequency the impoverishment of abiotic resources may favour male sexual expression in plants as it is less costly than female expression. Also, fire can modify pollinator communities and thus affect plant reproduction. Here we evaluate the effect of frequent fires on sexual expression, pollination and reproductive success of Vachellia caven (Leguminosae), an andromonoecious tree that is highly dependent on animal pollination and is abundant in burned sites. We expect that increased fire frequency will favour maleness but it will decrease reproductive success due to abiotic resource depletion in repeated burned sites. To test this, we selected focal plants in three unburned sites and three frequently burned sites and measured their sexual expression, basal diameter, pollination and fruit set. The proportion of male inflorescences per plant was not affected by fire and it was negatively related with the diameter of the plant. The proportion of pollinated flowers was not affected by fire, and fruit set increased with maleness only in frequently burned sites. These results indicate that V. caven is adapted to regimes of high fire frequency: not only was there similar fruit set in both burned and unburned sites, but more male plants had higher fruit set in burned sites. Despite the soil impoverishment triggered by repeated fires, V. caven is able to maintain its sexual and reproductive functions, allowing it to persist and maintain viable populations in fire‐prone environments.

Abstract in Spanish is available with online material.
The epigenetics of the hypothalamic‐pituitary‐adrenal axis in fetal development
Authors: Montenegro Yorran Hardman A. , de Queiroga Nascimento Denise , de Assis Thiago Oliveira , Santos‐Lopes Simone Silva Dos
Published: March 2019

The hypothalamic‐pituitary‐adrenal (HPA) axis is an important hormonal mechanism of the human body and is extremely programmable during embryonic and fetal development. Analyzing its development in this period is the key to understanding in fact how vulnerabilities of congenital diseases occur and any other changes in the phenotypic and histophysiological aspects of the fetus. The environment in which the mother is exposed during the gestational period can influence this axis. Knowing this, our objective was to analyze in recent research the possible impact of epigenetic programming on the HPA axis and its consequences for fetal development. This review brought together articles from two databases: ScienceDirect and PUBMED researched based on key words such as “epigenetics, HPA axis, cardiovascular disease, and circulatory problems” where it demonstrated full relevance in experimental and scientific settings. A total of 101 articles were selected following the criteria established by the researchers. Thus, it was possible to verify that the development of the HPA axis is directly related to changes that occur in the cardiovascular system, to the cerebral growth and other systems depending on the influence that it receives in the period of fetal formation.
First‐in‐human phase I study of infusional and bolus schedules of Deflexifol, a novel 5‐fluorouracil and leucovorin formulation, after failure of standard treatment
Authors: Clingan Philip R. , Ackland Stephen P. , Brungs Daniel , de Souza Paul , Aghmesheh Morteza , Garg Madhu B. , Ranson Richard D. , Parker Suzanne , Jokela Rebecca , Ranson Marie
Published: March 2019

Background

5‐Fluorouracil (5‐FU) is administered with leucovorin (LV) to enhance clinical activity. However, simultaneous administration is not feasible due to their chemical incompatibility, so conditions for the maximum possible beneficial interaction cannot be met. To overcome this, we developed a novel all‐in‐one, pH neutral stable solution of 5‐FU plus LV with β‐cyclodextrin (termed Deflexifol) and assessed its safety and tolerability in a first‐in‐human phase I trial.

Methods

Patients with advanced solid malignancy received Deflexifol as weekly bolus (375–575 mg/m²) or two‐weekly 46 h infusion (1200–3600 mg/m²) for six cycles in a 3+3 dose escalation design. Adverse events, pharmacokinetics and tumor response rates were assessed by standard methods.

Results

Forty patients were treated (19 bolus, 21 infusional, median age 67) with no grade 4 adverse events reported. Dose‐limiting toxicities of grade 3 diarrhea and myelosuppression were reported for the bolus schedule at 575 mg/m2 (maximum tolerated dose 525 mg/m²), whereas none were reported for the infusional schedule. The recommended phase II infusional dose was declared as 3,000 mg/m², >25% that of 5‐FU used in standard‐of‐care regimens. Pharmacokinetic analyses showed evidence of inter‐patient variability, with no evidence of saturation in clearance, and a trend to linear increase in AUC with dose. Disease control rate was 64% despite most patients having failed previous 5‐FU regimens.

Conclusion

Deflexifol is safer and effective in bolus and infusion schedules at higher doses than that permitted by separate infusion of 5‐FU and LV. A phase II study evaluating Deflexifol is planned.
Virtual internships in blended environments to prepare preservice teachers for the professional teaching context
Authors: Theelen H. , Willems M. C. , van den Beemt A. , Conijn R. , den Brok P.
Published: March 2019

This study investigated to what extent virtual internships in teacher education were able to reduce Preservice Teachers’ (PSTs) professional anxiety. Simultaneously, this study investigated how virtual internships in blended learning environments were evaluated by PSTs in terms of technological, social and educational affordances. PSTs followed virtual internships during two different Educational Pedagogy Master’s courses (27 and 16 participants) in a teacher education programme. A mixed methods design was employed, consisting of pre‐ and post‐test questionnaires, a focus group interview and individual interviews. A significant decrease was found in PSTs’ professional anxiety after having followed Virtual Internship 2. PSTs reported they obtained a more realistic image of teaching and felt better prepared for teaching in practice. Furthermore, regarding technological affordances, system usability was considered between acceptable and good. Concerning social affordances, PSTs appreciated collaboration within the virtual internships. As an educational affordance, it appeared that learning from videos with authentic classroom events is a good preparation for the professional teaching context. According to the PSTs, the scenarios within virtual internships could be improved in terms of authenticity and personalisation by offering more details and background information. The results of this study imply that virtual internships can be useful assets for teacher education.
Discontinuation of imatinib in children with chronic myeloid leukaemia in sustained deep molecular remission: results of the STOP IMAPED study
Authors: de Bruijn Clara M. A. , Millot Frédéric , Suttorp Meinolf , Borisevich Marina , Brons Paul , Lausen Birgitte , de Bont Eveline S. J. M.
Published: March 2019

This international study aimed to assess the effect of imatinib discontinuation in paediatric patients with chronic myeloid leukaemia (CML) after deep molecular remission (DMR) had been achieved and maintained for at least 2 years. The primary endpoint of this analysis was the molecular relapse‐free survival, estimated by the non‐parametric Kaplan‐Meier method. Major endpoint was the estimated rate of patients without molecular relapse at 6 months. Fourteen patients were enrolled; 4 patients maintained DMR with a follow‐up of 24 (two patients), 34 and 66 months, respectively, whereas 10 patients relapsed. All molecular relapses occurred within 6 months (median 3 months, range 1–6) after imatinib discontinuation. The overall probability of maintaining DMR at 6 months was 28·6%. No parameters associated with molecular relapse could be identified. Keeping in mind the rarity of paediatric CML, which contributed to the small size of the cohort, our findings illustrate that imatinib cessation after sustained DMR is successful in only limited numbers of patients, whereas much higher rates are reported in adult patients. Further research is needed to extend the cohort of paediatric CML patients who might achieve treatment‐free remission with an ideal prerequisite of predicting the occurrence of molecular relapse l after imatinib cessation.
Reactions to offenders: Psychological differences between beliefs versus punishment
Authors: Fousiani Kyriaki , van Prooijen Jan‐Willem
Published: March 2019

In the present research, we examined a discrepancy between people's beliefs about, versus punitive reactions towards, offenders. Particularly, appraisals of offenders along the dimension of communion (i.e., being friendly or trustworthy) should primarily affect people's beliefs about them, as reflected in demonizing and conspiracy theories, and to a lesser extent observers’ punitive reactions. However, actual evidence of transgression should (more strongly than beliefs) influence observers’ punitive reactions. In two studies, we manipulated communion and transgression ambiguity in the context of financial offences. The transgression was presented as either an observable and clear‐cut immoral case (non‐ambiguous transgression) or as a case that involves a grey area between what is legal or illegal (ambiguous transgression). Study 1 revealed that viewing an offender as low (as opposed to high) in communion predominantly influenced demonization and conspiracy beliefs involving the offender. The transgression manipulation, however, mostly influenced observers’ punitive reactions and their underlying punitive motives. Similar findings were obtained in Study 2. We conclude that although beliefs about offenders and punitive reactions are often strongly related, they are actually grounded in different psychological processes.
Hypoxia‐inducible factor‐1α and nuclear factor‐κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non‐small‐cell lung cancer cells
Authors: Guo Rong , Li Yong , Wang Zhijie , Bai Hua , Duan Jianchun , Wang Shuhang , Wang Lvhua , Wang Jie
Published: March 2019

Some driver gene mutations, including epidermal growth factor receptor (EGFR), have been reported to be involved in expression regulation of the immunosuppressive checkpoint protein programmed cell death ligand 1 (PD‐L1), but the underlying mechanism remains obscure. We investigated the potential role and precise mechanism of EGFR mutants in PD‐L1 expression regulation in non‐small‐cell lung cancer (NSCLC) cells. Examination of pivotal EGFR signaling effectors in 8 NSCLC cell lines indicated apparent associations between PD‐L1 overexpression and phosphorylation of AKT and ERK, especially with increased protein levels of phospho‐IκBα (p‐IκBα) and hypoxia‐inducible factor‐1α (HIF‐1α). Flow cytometry results showed stronger membrane co‐expression of EGFR and PD‐L1 in NSCLC cells with EGFR mutants compared with cells carrying WT EGFR. Additionally, ectopic expression or depletion of EGFR mutants and treatment with EGFR pathway inhibitors targeting MEK/ERK, PI3K/AKT, mTOR/S6, IκBα, and HIF‐1α indicated strong accordance among protein levels of PD‐L1, p‐IκBα, and HIF‐1α in NSCLC cells. Further treatment with pathway inhibitors significantly inhibited xenograft tumor growth and p‐IκBα, HIF‐1α, and PD‐L1 expression of NSCLC cells carrying EGFR mutant in nude mice. Moreover, immunohistochemical analysis revealed obviously increased protein levels of p‐IκBα, HIF‐1α, and PD‐L1 in NSCLC tissues with EGFR mutants compared with tissues carrying WT EGFR. Non‐small‐cell lung cancer tissues with either p‐IκBα or HIF‐1α positive staining were more likely to possess elevated PD‐L1 expression compared with tissues scored negative for both p‐IκBα and HIF‐1α. Our findings showed important roles of phosphorylation activation of AKT and ERK and potential interplay and cooperation between NF‐κB and HIF‐1α in PD‐L1 expression regulation by EGFR mutants in NSCLC.
Addressing Sexism With Children: Young Adults’ Beliefs About Bias Socialization
Authors: Hilliard Lacey J. , Liben Lynn S.
Published: March 2019

College students’ beliefs concerning socializing children about sexism and other culturally important topics were investigated using mixed methods. In Study 1, participants (N = 71) defined sexism and explained their beliefs about addressing sexism with children. Thirty‐five percent argued against childhood sexism‐socialization. Emergent themes provided insights about how sexism is viewed and yielded data needed to design a closed‐ended socialization‐beliefs survey. In Study 2, students (N = 141) completed this survey and reported their feminist beliefs and childhood‐socialization experiences. Childhood sexism‐socialization was more commonly endorsed by women, stronger feminists, and those who had themselves experienced childhood sexism‐socialization. Descriptive data document socialization beliefs about 21 culturally important topics. Results suggest that programs aimed at socializing children about sexism should also address beliefs of the adults responsible for program implementation.
Predation on wild and hatchery salmon by non‐native brown trout (Salmo trutta) in the Trinity River, California
Authors: Alvarez Justin S. , Ward Darren M.
Published: March 2019

Non‐native predators may interfere with conservation efforts for native species. For example, fisheries managers have recently become concerned that non‐native brown trout may impede efforts to restore native salmon and trout in California's Trinity River. However, the extent of brown trout predation on these species is unknown. We quantified brown trout predation on wild and hatchery‐produced salmon and trout in the Trinity River in 2015. We first estimated the total biomass of prey consumed annually by brown trout using a bioenergetics model and measurements of brown trout growth and abundance over a 64‐km study reach. Then, we used stable isotope analysis and gastric lavage to allocate total consumption to specific prey taxa. Although hatchery‐produced fish are primarily released in the spring, hatchery fish accounted for most of the annual consumption by large, piscivorous brown trout (>40 cm long). In all, the 1579 (95% CI 1,279–1,878) brown trout >20 cm long in the study reach ate 5,930 kg (95% CI 3,800–8,805 kg) of hatchery fish in 2015. Brown trout predation on hatchery fish was ca. 7% of the total biomass released from the hatchery. Brown trout only ate 924 kg (95% CI 60–3,526 kg) of wild fish in 2015, but this was potentially a large proportion of wild salmon production because wild fish were relatively small. As large brown trout rely heavily on hatchery‐produced fish, modifying hatchery practices to minimise predation may enhance survival of hatchery fish and potentially reduce the abundance of predatory brown trout.
Earlier migration and distribution changes of albacore in the Northeast Atlantic
Authors: Chust Guillem , Goikoetxea Nerea , Ibaibarriaga Leire , Sagarminaga Yolanda , Arregui Igor , Fontán Almudena , Irigoien Xabier , Arrizabalaga Haritz
Published: March 2019

Marine species have exhibited trends in their geographic distribution and phenology in recent decades, and these changes are triggered by climate variability or anthropogenic pressures. Northeast Atlantic albacore has recently been identified to show changes of this nature, although the underlying causes are still uncertain. The aim of this work was to analyse the Northeast Atlantic albacore distribution shifts and phenological changes during the trophic migration that juveniles undertake from late spring to autumn and to identify potential causes of such variability. Specifically, time series of albacore catches of the Basque trolling fleet were studied and compared with trends derived from a null ecological niche model using very large number of catch observations (27,982). The results showed an earlier albacore migration of 2.3 days per decade during the period of 1981–2017, which was partly associated with the recent warming of the sea. The trend analysis of the catch distribution also detected a significant north‐westward trend in catch observations and a northward trend in species habitat. In contrast, both latitudinal trends were uncorrelated. This result suggests that interannual species distribution shifts are mainly related to factors other than oceanic‐climatic variability, such as fleet behaviour or prey changes.
Dispersion of vendace eggs and larvae around potential nursery areas reveals their reproductive strategy
Authors: Karjalainen Juha , Juntunen Janne , Keskinen Tapio , Koljonen Saija , Nyholm Kristiina , Ropponen Janne , Sjövik Rosanna , Taskinen Salla , Marjomäki Timo J.
Published: March 2019

Depending on their reproductive strategy, different fish species aim to aggregate or disperse eggs and larvae in their reproductive habitat. Many pelagic species disperse their eggs widely around the potential nursery areas. Larval dispersion or aggregation affects population sub‐structuring, which has important implications in fisheries management and conservation of the natural spatial diversity in populations.

The dispersion of larval vendace (Coregonus albula) was quantified in two oligotrophic Finnish lakes, and effects of density and environmental variables on the inter‐annual variation in the larval distribution were examined by analysing spatial abundance data from the lakes from 1999 to 2017. A 3‐D hydrodynamic egg distribution model was used to simulate the larval transport after hatching.

Vendace larvae dispersed lake‐wide to both littoral and pelagic zones but, in some littoral hot spots, more larvae aggregated year after year. However, in years of high larval number, the densities increased not only in the hot spots, but generally at all sampling plots. An overall increase in abundance was observed at all sampling sites. The simulations of the egg distribution model supported the hypothesis that the dispersion of the eggs occurs by spawners, i.e. by spawning at several different spawning sites, which are located all around the lake.

The dispersion of vendace eggs and larvae can be seen as a bet‐hedging strategy in space and time since in boreal oligotrophic large lakes with fragmented morphology, weather and other environmental factors in spring during hatching varies from year to year spatially in unpredictable manner. Lake‐wide larval dispersion suggests that the subpopulations of adjacent lake deeps may swap considerable amounts of individuals during early life and may not be closed units. Conservation of particular habitats seems unnecessary for Finnish vendace populations where large potential spawning areas in lakes are available.
Pyrite Oxidation Halts Migration of a Phosphorus Plume
Authors: Robertson William D. , Garda Dorothy L.
Published: March 2019

We have established a monitoring record of phosphate (PO43−) migration in the Long Point, ON campground septic system plume that now spans 26 years. Previously, at year 16 (2006), a P plume 16 m in length was documented and provided a good fit with an analytical advection dispersion model when a P migration velocity of 0.8 m/yr was used (retardation factor of 37) and when P behaved in an otherwise conservative manner (sorption only). However, between years 16 and 26 (2016), the P plume length expanded by only 2 m (0.2 m/yr) and increased in depth by only 0.5 m. The zone of abrupt P depletion at depth occurs close to the zone where SO42− concentrations increase in response to NO3− oxidation of pyrite. Scanning electron microscope images of sand grains from the nose of the P plume reveal abundant authigenic mineral coatings of considerable thickness (∼5 to 20 μm), with Fe as the dominant cation and containing 1 to 3 wt % P. This evidence suggests that P is now being attenuated along a reaction front that coincides with the zone where pyrite oxidation is occurring. P migration may now be controlled by the rate of migration of the pyrite oxidation front and this is several times slower than the previously indicated rate in the shallower, sorption‐controlled portion of the plume. Monitoring at Long Point has demonstrated the danger of embracing an overly simplistic conceptual model when attempting to predict wastewater P migration in groundwater and also highlights the unique insight provided by a long‐term monitoring record.
The Development of Object Construction From Infancy Through Toddlerhood
Authors: Marcinowski Emily C. , Nelson Eliza , Campbell Julie M. , Michel George F.
Published: March 2019

Early in development, children explore and combine objects in increasingly complex ways. One manual skill, object construction, represents a major shift in how objects are explored relative to other objects. Despite recent connections with cognitive functioning such as spatial skills, the development of object construction ability has rarely been studied and its trajectory has not been adequately described. The purpose of this study was to describe the development of three types of object construction (stacking, nesting, and affixing) across 5 monthly infant visits and 7 monthly toddler visits using a longitudinal design and a large sample size. Infants (10–14 months, n = 131) and toddlers drawn from the infant sample (18–24 months, n = 65) were given sets of age‐appropriate toys each of which elicited at least one type of constructive play. We described success at different construction tasks and identified trends for construction skill for infant and toddler development using multilevel modeling. We found that each of the three construction actions developed in unique ways across the 10‐ to 24‐month period. Infant construction skill predicted the development of toddler skill, but toddler construction skill diverged from infant trajectories. We discuss the role of combination strategies in the development of object construction skill and how object construction could be related to other domains of development.
A column‐generation‐based approach to fleet design problems mixing owned and hired vehicles
Authors: Bertoli Francesco , Kilby Philip , Urli Tommaso
Published: March 2019

We look at the problem of choosing a fleet of vehicles to carry out delivery tasks across a long time horizon. The delivery quantities may vary significantly from day to day, and from season to season, and the underlying routing problem may have rich constraints, for example, time windows, multiple compartments, multiple commodities, and compatibility constraints. We consider the option of hiring extra vehicles from external carriers in order to efficiently carry out the day‐to‐day operations while containing the costs of owning the fleet. The goal is to design a fleet so as to minimize the sum of costs of routing the fleet every day of the horizon, the acquisition costs, the maintenance costs, and the costs of hiring external vehicles. In the literature, there is no previous work on fleet design for a long time horizon, which also considers the hiring options. We propose to tackle the problem using column generation and develop three different heuristics. The methods proposed are tested and compared on a set of real‐world problems. It is also shown how introducing the possibility of hiring helps reducing the overall cost and the number of idle vehicles over the planning horizon.
Empirical surveys of frontier applications: a meta‐review
Authors: Daraio Cinzia , Kerstens Kristiaan , Nepomuceno Thyago , Sickles Robin C.
Published: March 2019

This contribution is the first attempt to systematically review all empirical surveys that so far have been made available in the broad field of efficiency and productivity analysis using frontier estimation methodologies. We provide a systematic bibliometric review on the many empirical surveys in the field of efficiency and productivity analysis, the most relevant concepts, areas, overlaps, and potentials to explore from its introduction to the most recent surveys. We combine the United Nations’ International Standard Industrial Classification (ISIC) taxonomy for the economic activity with the Journal of Economic Literature (JEL) classification system to classify the empirical surveys and to identify the current gaps in the literature. In addition to the most relevant/generic potential areas for applications (according to the United Nation's ISIC), this methodology provides a cluster analysis with the most relevant concepts that have been considered so far (according to the JEL codes). This overview brings an interesting guide for future work to develop the whole field.