bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological approaches for hypertrophic scars
Authors: Lingzhi Zhong , Meirong Li , Xiaobing Fu 
Published: December 2019

AbstractScar formation is usually the pathological consequence of skin trauma. And hypertrophic scars (HSs) frequently occur in people after being injured deeply. HSs are unusually considered as the result of tissue contraction and excessive extracellular matrix component deposition. Myofibroblasts, as the effector cells, mainly differentiated from fibroblasts, play the crucial role in the pathophysiology of HSs. A number of growth factors, inflammatory cytokines involved in the process of HS occurrence. Currently, with in‐depth exploration and clinical research of HSs, various creative and effective treatments budded. In here, we summarize the progress in the molecular mechanism of HSs, and review the available biotherapeutic methods for their pathophysiological characteristics. Additionally, we further prospected that the comprehensive therapy may be more suitable for HS treatment.
Utilizing TiO2 amorphous precursors for polymorph selection: An in situ TEM study of phase formation and kinetics
Authors: Mangum John S. , Garten Lauren M. , Ginley David S. , Gorman Brian P. 
Published: December 2019

AbstractSelective synthesis of metastable polymorphs requires a fundamental understanding of the complex energy landscapes in which these phases form. Recently, the development of in situ high temperature and controlled atmosphere transmission electron microscopy has enabled the direct observation of nucleation, growth, and phase transformations with near atomic resolution. In this work, we directly observe the crystallization behavior of amorphous TiO2 thin films grown under different pulsed laser deposition conditions and quantify the mechanisms behind metastable crystalline polymorph stabilization. Films deposited at 10 mTorr chamber oxygen pressure crystallize into nanocrystalline Anatase at 325°C, whereas films deposited at 2 mTorr crystallize into significantly larger needle‐like grains of Brookite and Anatase at 270°C. Increasing film deposition rate by a factor of 4 results in a 10× increase in the crystalline growth front velocity as well as a decrease in crystallization temperature from 270°C to 225°C. Engineering the amorphous precursor state through deposition conditions therefore provides routes to microstructure control and the accessibility of higher energy metastable phases.
Profit shifting and tax‐rate uncertainty
Authors: Delis Manthos D. , Hasan Iftekhar , Karavitis Panagiotis I. 
Published: December 2019

AbstractUsing firm‐level data for 1,084 parent firms in 24 countries and for 9,497 subsidiaries in 54 countries, we show that tax‐motivated profit shifting is larger among subsidiaries in countries that have stable corporate tax rates over time. Our findings further suggest that firms move away from transfer pricing and toward intragroup debt shifting that has lower adjustment costs. Our results are robust to several identification methods and respecifications, and they highlight the important role of tax‐rate uncertainty in the profit‐shifting decision while pointing to an adjustment away from more costly transfer pricing and toward debt shifting.
Relationship between polycomb‐group protein BMI‐1 and phosphatases regulating AKT phosphorylation level in endometrial cancer
Authors: Zaczek Agnieszka , Jóźwiak Paweł , Ciesielski Piotr , Forma Ewa , Wójcik‐Krowiranda Katarzyna , Cwonda Łukasz , Bieńkiewicz Andrzej , Bryś Magdalena , Krześlak Anna 
Published: December 2019

AbstractThe PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI‐1 (B‐lymphoma Mo‐MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI‐1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non‐neoplastic endometrial tissue by Western blot and RT‐PCR, respectively. The impact of BMI‐1 down‐regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI‐1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine‐rich repeat protein phosphatases 1/2) expression and decrease in phospho‐AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI‐1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI‐1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI‐1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI‐1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.
Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model
Authors: Zalles Michelle , Smith Nataliya , Ziegler Jadith , Saunders Debra , Remerowski Shannon , Thomas Lincy , Gulej Rafal , Mamedova Nadya , Lerner Megan , Fung Kar‐Ming , Chung Junho , Hwang Kyusang , Jin Junyeong , Wiley Graham , Brown Chase , Battiste James , Wren Jonathan D. , Towner Rheal A. 
Published: December 2019

AbstractGlioblastoma is an aggressive brain tumour found in adults, and the therapeutic approaches available have not significantly increased patient survival. Recently, we discovered that ELTD1, an angiogenic biomarker, is highly expressed in human gliomas. Polyclonal anti‐ELTD1 treatments were effective in glioma pre‐clinical models, however, pAb binding is potentially promiscuous. Therefore, the aim of this study was to determine the effects of an optimized monoclonal anti‐ELTD1 treatment in G55 xenograft glioma models. MRI was used to assess the effects of the treatments on animal survival, tumour volumes, perfusion rates and binding specificity. Immunohistochemistry and histology were conducted to confirm and characterize microvessel density and Notch1 levels, and to locate the molecular probes. RNA‐sequencing was used to analyse the effects of the mAb treatment. Our monoclonal anti‐ELTD1 treatment significantly increased animal survival, reduced tumour volumes, normalized the vasculature and showed higher binding specificity within the tumour compared with both control‐ and polyclonal‐treated mice. Notch1 positivity staining and RNA‐seq results suggested that ELTD1 has the ability to interact with and interrupt Notch1 signalling. Although little is known about ELTD1, particularly about its ligand and pathways, our data suggest that our monoclonal anti‐ELTD1 antibody is a promising anti‐angiogenic therapeutic in glioblastomas.
Osa‐miR1873 fine‐tunes rice immunity against Magnaporthe oryzae and yield traits
Authors: Zhou Shi‐Xin , Zhu Yong , Wang Liang‐Fang , Zheng Ya‐Ping , Chen Jin‐Feng , Li Ting‐Ting , Yang Xue‐Mei , Wang He , Li Xu‐Pu , Ma Xiao‐Chun , Zhao Ji‐Qun , Pu Mei , Feng Hui , Li Yan , Fan Jing , Zhang Ji‐Wei , Huang Yan‐Yan , Wang Wen‐Ming 
Published: December 2019

AbstractMicroRNAs (miRNAs) are known to fine‐tune growth, development, and stress‐induced responses. Osa‐miR1873 is a rice‐specific miRNA targeting LOC_Os05g01790. Here, we show that Osa‐miR1873 fine‐tunes rice immunity against Magnaporthe oryzae and yield traits via LOC_Os05g01790. Osa‐miR1873 was significantly upregulated in a susceptible accession but downregulated in a resistance accession at 24 h post‐inoculation (hpi) of M. oryzae. Overexpressing Osa‐miR1873 enhanced susceptibility to M. oryzae and compromised induction of defense responses. In contrast, blocking Osa‐miR1873 through target mimicry compromised susceptibility to M. oryzae and enhanced induction of defense responses. Altered expression of Osa‐miR1873 also resulted in some defects in yield traits, including grain numbers and seed setting rate. Moreover, overexpression of the target gene LOC_Os05g01790 increased rice blast disease resistance but severely penalized growth and yield. Taken together, we demonstrate that Osa‐miR1873 fine‐tunes the rice immunity‐growth trade‐off via LOC_Os05g01790, and blocking Osa‐miR1873 could improve blast disease resistance without significant yield penalty. Thus, the Osa‐miR1873‐LOC_Os05g01790 regulatory module is valuable in balancing yield traits and blast resistance.
The Business Model of Social Banks
Authors: Cornée Simon , Kalmi Panu , Szafarz Ariane 
Published: December 2019

SUMMARYBased on an extensive literature review, this paper proposes to define social banks (SBs) as social enterprises that run banking activities with the social mission of supplying credit to other social enterprises, which are typically less profitable than for‐profit businesses. This definition marks our starting point for developing a theoretical framework to explain how SBs survive without subsidies in the banking market. We build on a two‐pillar business model of value‐based financial intermediation, which comprises an ownership structure that limits residual ownership claims and preferential credit conditions associated with financial sacrifices from motivated depositors. We also clarify the link between SBs and stakeholder banks and weigh up the importance of market interest rates for facilitating the business of SBs. An empirical analysis based on panel regressions on 5,400 European banks over the 1998‐2013 period attests to the relevance of our theoretical framework. It also confirms that a low interest rate environment raises concerns about the sustainability of the SB business model.
Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false‐positive antibodies
Authors: Llovet Laura‐Patricia , Gratacós‐Ginés Jordi , Ortiz Oswaldo , Rodriguez‐Tajes Sergio , Lens Sabela , Reverter Enric , Ruiz‐Ortiz Estibaliz , Costa Josep , Viñas Odette , Forns Xavier , Parés Albert , Londoño María‐Carlota 
Published: December 2019

AbstractBackground and aimsRecent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti‐HEV IgM and IgG, and HEV‐RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti‐HEV serology.MethodsOne hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non‐AIH).ResultsSeroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non‐AIH). Patients with acute AIH and positive anti‐HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti‐HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021).ConclusionSeroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross‐reactivity between HEV and liver antigens.
The microbiota influences the Drosophila melanogaster life history strategy
Authors: Walters Amber W. , Hughes Rachel C. , Call Tanner B. , Walker Carson J. , Wilcox Hailey , Petersen Samara C. , Rudman Seth M. , Newell Peter D. , Douglas Angela E. , Schmidt Paul S. , Chaston John M. 
Published: December 2019

AbstractOrganisms are locally adapted when members of a population have a fitness advantage in one location relative to conspecifics in other geographies. For example, across latitudinal gradients, some organisms may trade off between traits that maximize fitness components in one, but not both, of somatic maintenance or reproductive output. Latitudinal gradients in life history strategies are traditionally attributed to environmental selection on an animal's genotype, without any consideration of the possible impact of associated microorganisms (“microbiota”) on life history traits. Here, we show in Drosophila melanogaster, a key model for studying local adaptation and life history strategy, that excluding the microbiota from definitions of local adaptation is a major shortfall. First, we reveal that an isogenic fly line reared with different bacteria varies the investment in early reproduction versus somatic maintenance. Next, we show that in wild fruit flies, the abundance of these same bacteria was correlated with the latitude and life history strategy of the flies, suggesting geographic specificity of the microbiota composition. Variation in microbiota composition of locally adapted D. melanogaster could be attributed to both the wild environment and host genetic selection. Finally, by eliminating or manipulating the microbiota of fly lines collected across a latitudinal gradient, we reveal that host genotype contributes to latitude‐specific life history traits independent of the microbiota and that variation in the microbiota can suppress or reverse the differences between locally adapted fly lines. Together, these findings establish the microbiota composition of a model animal as an essential consideration in local adaptation.
Conceptualising spaced learning in health professions education: A scoping review
Authors: Versteeg Marjolein , Hendriks Renée A. , Thomas Aliki , Ommering Belinda W. C. , Steendijk Paul 
Published: December 2019

AbstractObjectivesTo investigate the definitions and applications of ‘spaced learning’ and to propose future directions for advancing its study and practice in health professions education.MethodThe authors searched five online databases for articles published on spaced learning in health professions education prior to February 2018. Two researchers independently screened articles for eligibility with set inclusion criteria. They extracted and analysed key data using both quantitative and qualitative methods.ResultsOf the 2972 records retrieved, 120 articles were included in the review. More than 90% of these articles were published in the last 10 years. The definition of spaced learning varied widely and was often not theoretically grounded. Spaced learning was applied in distinct contexts, including online learning, simulation training and classroom settings. There was a large variety of spacing formats, ranging from dispersion of information or practice on a single day, to intervals lasting several months. Generally, spaced learning was implemented in practice or testing phases and rarely during teaching.ConclusionsSpaced learning is infrequently and poorly defined in the health professions education literature. We propose a comprehensive definition of spaced learning and emphasise that detailed descriptions of spacing formats are needed in future research to facilitate the operationalisation of spaced learning research and practice in health professions education.
Epigenetic control of tumor angiogenesis
Authors: Ribatti Domenico , Tamma Roberto 
Published: December 2019

AbstractThe term “epigenetic” is used to refer to heritable alterations in chromatin that are not due to changes in DNA sequence. Different growth factors and vascular genes mediate the angiogenic process, which is regulated by epigenetic states of genes. The aim of this article is to analyze the role of epigenetic mechanisms in the control and regulation of tumor angiogenetic processes. The reversibility of epigenetic events in contrast to genetic aberrations makes them potentially suitable for therapeutic intervention. In this context, DNA methyltransferase (DNMT) and HDAC inhibitors indirectly—via the tumor cells—exhibit angiostatic effects in vivo, and inhibition of miRNAs can contribute to the development of novel anti‐angiogenesis therapies.
Objectivity in rare disease research: A philosophical approach
Authors: Hews‐Girard Julia , Obilar Helen N. , Camargo Plazas Pilar 
Published: December 2019

AbstractIndividuals living with rare conditions are faced with important challenges derived from the rarity of their conditions and aggravated by the low priority given to rare disease research. However, current realities of rare disease research require consideration of the relationship between subjectivity and ‘traditional’ objectivity. Objectivity in research has traditionally been associated with processes and descriptions that are independent of the investigator. The need for researchers to provide unbiased knowledge and achieve a balance between objectivity and the underlying values in nursing and scientific research requires an examination of how objectivity is conceptualized within the context of rare disease research. The aim of this paper is to examine scientific objectivity in rare disease research from a philosophical viewpoint and, in doing so, demonstrate the need to redefine it to reflect the current scientific environment. As such, healthcare providers working on this field need to redefine objectivity around ethical and moral obligation to advance science in an equitable manner with the end goal to produce knowledge that is trustworthy and beneficial to our patients.
Conditioning the soil microbiome through plant–soil feedbacks suppresses an aboveground insect pest
Authors: Pineda Ana , Kaplan Ian , Hannula S. Emilia , Ghanem Wadih , Bezemer T. Martijn 
Published: December 2019

Summary

Soils and their microbiomes are now recognized as key components of plant health, but how to steer those microbiomes to obtain their beneficial functions is still unknown. Here, we assess whether plant–soil feedbacks can be applied in a crop system to shape soil microbiomes that suppress herbivorous insects in above‐ground tissues.

We used four grass and four forb species to condition living soil. Then we inoculated those soil microbiomes into sterilized soil and grew chrysanthemum as a focal plant. We evaluated the soil microbiome in the inocula and after chrysanthemum growth, as well as plant and herbivore parameters.

We show that inocula and inoculated soil in which a focal plant had grown harbor remarkably different microbiomes, with the focal plant exerting a strong negative effect on fungi, especially arbuscular mycorrhizal fungi. Soil inoculation consistently induced resistance against the thrips Frankliniella occidentalis, but not against the mite Tetranychus urticae, when compared with sterilized soil. Additionally, plant species shaped distinct microbiomes that had different effects on thrips, chlorogenic acid concentrations in leaves and plant growth.

This study provides a proof‐of‐concept that the plant–soil feedback concept can be applied to steer soil microbiomes with the goal of inducing resistance above ground against herbivorous insects.
Mutant analysis in the nonlegume Parasponia andersonii identifies NIN and NF‐YA1 transcription factors as a core genetic network in nitrogen‐fixing nodule symbioses
Authors: Bu Fengjiao , Rutten Luuk , Roswanjaya Yuda Purwana , Kulikova Olga , Rodriguez‐Franco Marta , Ott Thomas , Bisseling Ton , van Zeijl Arjan , Geurts Rene 
Published: December 2019

Summary

Nitrogen‐fixing nodulation occurs in 10 taxonomic lineages, with either rhizobia or Frankia bacteria. To establish such an endosymbiosis, two processes are essential: nodule organogenesis and intracellular bacterial infection. In the legume–rhizobium endosymbiosis, both processes are guarded by the transcription factor NODULE INCEPTION (NIN) and its downstream target genes of the NUCLEAR FACTOR Y (NF‐Y) complex.

It is hypothesized that nodulation has a single evolutionary origin c. 110 Ma, followed by many independent losses. Despite a significant body of knowledge of the legume–rhizobium symbiosis, it remains elusive which signalling modules are shared between nodulating species in different taxonomic clades. We used Parasponia andersonii to investigate the role of NIN and NF‐YA genes in rhizobium nodulation in a nonlegume system.

Consistent with legumes, P. andersonii PanNIN and PanNF‐YA1 are coexpressed in nodules. By analyzing single, double and higher‐order CRISPR‐Cas9 knockout mutants, we show that nodule organogenesis and early symbiotic expression of PanNF‐YA1 are PanNIN‐dependent and that PanNF‐YA1 is specifically required for intracellular rhizobium infection.

This demonstrates that NIN and NF‐YA1 have conserved symbiotic functions. As Parasponia and legumes diverged soon after the birth of the nodulation trait, we argue that NIN and NF‐YA1 represent core transcriptional regulators in this symbiosis.
Humans in the cold: Regulating energy balance
Authors: McInnis Kurt , Haman François , Doucet Éric 
Published: December 2019

SummaryFor humans to maintain a stable core temperature in cold environments, an increase in energy expenditure (EE) is required. However, little is known about how cold stimulus impacts energy balance as a whole, as energy intake (EI) has been largely overlooked. This review focuses on the current state of knowledge regarding how cold exposure (CE) impacts both EE and EI, while highlighting key gaps and shortcomings in the literature. Animal models clearly reveal that CE produces large increases in EE, while decreasing environmental temperatures results in a significant negative dose‐response effect in EI (r=‐.787, P<.001), meaning animals eat more as temperature decreases. In humans, multiple methods are used to administer cold stimuli, which result in consistent yet quantitatively small increases in EE. However, only two studies have measured ad libitum food intake in combination with acute CE in humans. Chronic CE (i.e., cold acclimation) studies have been shown to produce minimal changes in body weight, with an average compensation of ~126%. Although more studies are required to investigate how cold impacts EI in humans, results presented in this review warrant caution before presenting or considering CE as a potential adjunct to weight loss strategies.
Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice
Authors: Xu Jue , Wang Linyan , Huang Zhen , Chen YiPing , Shao Meiying 
Published: December 2019

AbstractObjectiveFibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis.Materials and MethodsDmp1Cre;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined.ResultsOsteocytes of maxillomandibular bones were found Dmp1‐positive prenatally, and Fgf8 over‐expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers.ConclusionsAugmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.