bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of microsatellite instability‐high hepatocellular carcinoma among Japanese patients and response to pembrolizumab
Authors: Kawaoka Tomokazu , Ando Yuwa , Yamauchi Masami , Suehiro Yosuke , Yamaoka Kenji , Kosaka Yumi , Fuji Yasutomo , Uchikawa Shinsuke , Morio Kei , Fujino Hatsue , Nakahara Takashi , Ono Atsushi , Murakami Eisuke , Takahashi Shoichi , Tsuge Masataka , Hiramatsu Akira , Imamura Michio , Chayama Kazuaki , Aikata Hiroshi 
Published: February 2020

AimPembrolizumab has been quickly approved in many countries for the treatment of patients with unresectable or metastatic, microsatellite instability‐high (MSI‐H) solid tumors, which have progressed following previous treatment and who have no satisfactory alternative treatment options. We aimed to determine the incidence of MSI‐H tumors in Japanese patients with advanced hepatocellular carcinoma (HCC).MethodsWe investigated the incidence of MSI‐H tumors in 82 consecutive Japanese patients with unresectable HCC that had progressed after standard of care treatment. Using a companion diagnostic sequencing kit (polymerase chain reaction analysis of five microsatellite markers: BAT25, BAT26, NR21, NR24 and MONO27), we analyzed 49 biopsy specimens and 33 resection specimens. Responses to pembrolizumab were assessed with the modified Response Evaluation Criteria in Solid Tumors.ResultsMSI‐H tumors were found in only two patients (2.4%), in whom all five markers showed slight shortening. One patient had a complete response to pembrolizumab for over 10 months, and the other was a non‐responder.ConclusionsMSI‐H tumor status was found in only two of 82 (2.4%) Japanese patients with advanced HCC, one of whom had a complete response to pembrolizumab. Thus, MSI status should be assessed in patients with HCC who progress after standard of care treatment.
Cistanche deserticola polysaccharide induces melanogenesis in melanocytes and reduces oxidative stress via activating NRF2/HO‐1 pathway
Authors: Hu Yibo , Huang Jinhua , Li Yixiao , Jiang Ling , Ouyang Yujie , Li Yumeng , Yang Lun , Zhao Xiaojiao , Huang Lihua , Xiang Hong , Chen Jing , Zeng Qinghai 
Published: February 2020

AbstractAs a main part of pigmentation disorders, skin depigmentation diseases such as vitiligo and achromic naevus are very common and get more attention now. The pathogenesis of depigmentation includes melanocyte dysfunction and loss, which are possibly caused by heredity, autoimmunity and oxidative stress. Among them, oxidative stress plays a key role; however, few clinical treatments can deal with oxidative stress. As reported, Cistanche deserticola polysaccharide (CDP) is an effective antioxidant; based on that, we evaluated its role in melanocyte and further revealed the mechanisms. In this study, we found that CDP could promote melanogenesis in human epidermal melanocytes (HEMs) and mouse melanoma B16F10 cells, it also induced pigmentation in zebrafish. Furthermore, CDP could activate mitogen‐activated protein kinase (MAPK) signal pathway, then up‐regulated the expression of microphthalmia‐associated transcription factor (MITF) and downstream genes TYR, TRP1, TRP2 and RAB27A. Otherwise, we found that CDP could attenuate H2O2‐induced cytotoxicity and apoptosis in melanocytes. Further evidence revealed that CDP could enhance NRF2/HO‐1 antioxidant pathway and scavenge intracellular ROS. In summary, CDP can promote melanogenesis and prevent melanocytes from oxidative stress injury, suggesting that CDP helps maintain the normal status of melanocytes. Thus, CDP may be a novel drug for the treatment of depigmentation diseases.
A study of organizational cynicism and how it is affected by social exchange relationships at work
Authors: Pfrombeck Julian , Doden Wiebke , Grote Gudela , Feierabend Anja 
Published: February 2020

Drawing on the social exchange theory, organizational cynicism has been suggested as a central consequence of psychological contract (PC) breach. In this study, we examine the extent to which social exchange relationships with the supervisor and coworkers have an impact on cynical reactions to broken employer promises. Based on two‐wave data with a time lag of three months from a sample of 781 employees, we investigated the influence of employees’ perceived PC breach on cynical thoughts, emotions, and behaviours, and the moderating effects of leader–member exchange (LMX) and coworker exchange (CWX). Using structural equation modelling, we found that PC breach was positively associated with cognitive, affective, and behavioural cynicism. Our analysis further revealed that LMX and CWX moderated different dimensions of organizational cynicism: When LMX was high, employees reacted more sensitively to a PC breach with cognitive and behavioural cynicism. In contrast, CWX attenuated employees’ affective cynical response to a PC breach. The differentiated perspective on cognitive, affective, and behavioural cynicism and the identified moderating effects help explain varying strengths of the PC breach–organizational cynicism association found in previous research and highlight contingencies related to social exchange relationships at work.Practitioner pointsThis study shows that cynicism towards the organization varies with the extent of perceived PC breach, indicating that organizations should actively manage employees’ psychological contracts.LMX tends to reduce cynicism towards the organization (direct effect), but high LMX employees seem to react more sensitively to severe PC breaches (interaction effect). Thus, high LMX cannot completely compensate employees’ cynical reaction to a PC breach. Leaders should be made aware of that and should be trained to effectively manage employees’ expectations to prevent PC breaches.Employees’ cynical emotional reaction to severe PC breaches was buffered by high levels of CWX. Hence, organizations should foster interpersonal relationships among coworkers.
Combination of a biomolecule‐aided biphasic cryogel scaffold with a barrier membrane adhering PDGF‐encapsulated nanofibers to promote periodontal regeneration
Authors: Huang Ren‐Yeong , Tai Wei‐Chiu , Ho Ming‐Hua , Chang Po‐Chun 
Published: February 2020

AbstractObjective and BackgroundTo achieve periodontal regeneration, numerous investigations have concentrated on biomolecule supplement and optimization of bone substitute or barrier membrane. This study evaluated the benefit of combining these strategies for periodontal regeneration.MethodsBiphasic cryogel scaffold (BCS) composed of gelatin (ligament phase) and gelatin with beta‐tricalcium phosphate/hydroxyapatite (BH) (bone phase) was designed as tested bone substitute, and both enamel matrix derivatives (EMD) and bone morphogenetic protein‐2 (BMP‐2) were applied to formulate a biomolecule‐aided BCS (BBS). Functionally graded membrane (FGM) was designed as tested barrier membrane by adhering PDGF‐encapsulated poly(L‐lactide‐co‐D/L‐lactide) nanofibers on the conventional membrane (CM). BBS and FGM were characterized and tested for biocompatibility in vitro. Thirty 4 × 4 × 5 mm3 periodontal intrabony defects were created on 6 Beagle dogs. Each defect was evenly assigned to one of the following treatments including BH‐CM, BCS‐CM, BBS‐CM, BH‐FGM, BCS‐FGM, and BBS‐FGM, for 12 weeks. The therapeutic efficiency was assessed by micro‐CT and histology.ResultsBCS and FGM sustained the release of biomolecules. The viability of MSCs was maintained in both phases of BCS and was promoted while seeding on the PDGF‐encapsulated nanofibers. In CM‐covered sites, BBS showed significantly greater osteogenesis (P < .01) and early defect fill (P < .05) relative to BH. FGM significantly promoted osteogenesis (P < .05) in BH‐treated sites but showed limited benefit in BBS‐treated sites. On denuded roots, cementum deposition was evident in BBS‐treated sites.ConclusionsPDGF‐loaded FGM promoted periodontal osteogenesis, and BBS with EMD‐BMP‐2 had potential for reconstructing alveolar ridge, periodontal ligament, and cementum. FGM and BBS combination provided limited additional benefit.
Internalizing and Externalizing Behaviors of Children with Writing Disabilities
Authors: Jordan Rebecca L. P. , Fernandez Edmund P. , Costa Lara‐Jeane C. , Hooper Stephen R. 
Published: February 2020

AbstractStudents with specific learning disabilities (SLDs) are more likely to exhibit internalizing and externalizing behaviors than typically developing peers. Virtually none of the literature, however, reports on the behaviors of students at‐risk for writing disabilities (AR‐WD). We compared the behaviors of writers who are AR‐WD and typically developing writers (TDW) from first through fourth grade (N = 138). We found that students who are AR‐WD were only significantly different from TDW on Externalizing and Total Behaviors at Grade 2. These findings illustrate the benefits of studying behavior across different forms of SLD, as it appears that students ARWD do not consistently manifest significant behaviors, although interventions that simultaneously target writing and behavior may be warranted and mutually beneficial.
Aha! Taking on the myth that simulation‐derived surprise enhances learning
Authors: Monteiro Sandra , Sibbald Matthew 
Published: February 2020

AbstractObjectivesThis paper aims to discuss the recurring education‐related issue of the high‐fidelity simulation myth. In the current instantiation, educators erroneously believe that trainees benefit from authentic uncertainty and surprise in simulation‐based training. MethodsWe explore the origins of this myth within the experiential learning and social constructivism theories and propose an evidence‐based solution of transparent and guided instruction in simulation.ResultsConstructivist theories highlight meaning making as the benefit of inquiry and discovery learning strategies. Inappropriate translation of this epistemology into an element of curriculum design creates unfortunate unintended consequences. ConclusionsWe propose that the translation of constructivist theories of learning within simulation‐based education has resulted in a pervasive myth, which decrees that scenarios must introduce realistic tension or surprises to encourage exploration and insightful problem solving. We argue that this myth is masquerading as experiential learning. In this narrative review, we interpret our experiences and observations of simulation‐based education through our expertise in education science and curriculum design. We offer anecdotal evidence along with a review of selected literature to establish the presence of this previously undetected myth.
Producing the nation through philanthropy: Legitimising coethnic and prorefugee civic action in Hungary
Authors: Zakariás Ildikó , Feischmidt Margit 
Published: February 2020

AbstractThis paper explores interconnections between nationhood and philanthropy, namely, how philanthropy works as a domain of meaningful social practice framed by national ideologies and how interpretations born in the institutional contexts of philanthropy may play a central role in making sense of the nation. We observe how various divisions inherent in philanthropic practices—between helpers and the helped and between those who take part in helping as opposed to those who do not—become reflected in concepts of nationhood shaped by these activities. The study of two cases—first, the philanthropic actions of Hungarian citizens towards Hungarian minority communities in Ukraine and Romania, and second, humanitarian volunteer initiatives aimed at supporting refugees during the summer of 2015 in Hungary—makes it possible to understand how philanthropic practices become a site for reproducing competing definitions of nationhood.
Median Lingual Foramen, a new midmandibular cephalometric landmark
Authors: Vandekerckhove David , Deibel Dionne , Vinayahalingam Shankeeth , Claeys Gilles , Kwon Tae‐Geon , Bergé Stefaan , Xi Tong 
Published: February 2020

AbstractPurposeIn asymmetrical mandibles, it is often challenging to identify the mandibular midline. The median lingual foramen (MLF) is located at the midline of the anterior mandible. The purpose of this study is to evaluate the reproducibility of identifying the MLF compared to conventional landmarks on cone beam computed tomography's (CBCT's) to mark the mandibular midline.Material and MethodsTen symmetrical class II, 10 symmetrical class III, ten asymmetrical class II and 10 asymmetrical class III patients were included. On CBCTs, the cephalometric landmarks menton, pogonion, genial tubercle and MLF were identified twice by two observers.ResultsA high intra‐ and interobserver reproducibility was found for all landmarks, the highest being the MLF. The gain in accuracy is 0.998 mm, 0.824 mm and 0.361 mm compared to pogonion, genial tubercle and menton, respectively (P‐value <.05).ConclusionMLF is a reliable and reproducible landmark to indicate the midline of the mandible, particularly in Class II asymmetric mandibles.
Organizational Risk: “Muddling Through” 40 Years of Research
Authors: Pettersen Gould Kenneth 
Published: February 2020

AbstractThe recognition that organizations are a part of adverse outcomes has become commonplace in risk research. Social organization is a key theme in relation to risk minimization through institutional control and monitoring, and in how organizations are connected to society's perceptions of risk (beyond outcomes). The article reviews progress made in research on organizational risk over the last four decades and the contributions made to the field by fieldwork and descriptive approaches, understanding risk as partly determined by organizational context. A key issue for risk analysis is to figure out what these insights mean for risk professionals, such as while developing assessment methodologies and management approaches. Analysis of the literature shows that what to model if organizational factors are to be included in risk assessments remains as big a question as how to model. Integrating fieldwork and descriptive approaches for analyzing organizational risk, accidents, and safety is argued to be a main task for the risk analysis community.
Growth decomposition bias when accounting for heterogeneous regimes: Evidence from China
Authors: Liu Guanchun , Ma Shichang , Lee Chien‐Chiang , Xu Ming 
Published: February 2020

AbstractWhen exploring the logic why some economies grow faster than others, previous studies commonly assume that all economies follow a universal growth path. This paper explores the heterogeneity of growth regimes across economies and then investigates the decomposition bias of growth sources in traditional methods. Using a panel data of China's provinces, the empirical results show that a finite mixture model with three classes is best to describe the data, revealing that there are multiple growth regimes across provinces. Also, some provinces switch regimes over time while the others remain stable. Further, neglecting heterogeneous regimes overestimates the importance of factor endowment and underestimates the importance of sector productivity, while it does not greatly influence the importance of of factor market efficiency. In particular, the decomposition bias embodies in physical capital and energy input rather than labor. Our findings indicate that the existing literature may underestimate the contribution of sector productivity. Thus, it is critical to account for heterogeneous regimes when exploring the sources of economic growth.
Overexpression of chalcone isomerase in apple reduces phloridzin accumulation and increases susceptibility to herbivory by two‐spotted mites
Authors: Dare Andrew P. , Tomes Sumathi , McGhie Tony K. , van Klink John W. , Sandanayaka Manoharie , Hallett Ian C. , Atkinson Ross G. 
Published: February 2020

SummaryApples (Malus spp.) accumulate significant quantities of the dihydrochalcone glycoside, phloridzin, whilst pears (Pyrus spp.) do not. To explain this difference, we hypothesized that a metabolic bottleneck in the phenylpropanoid pathway might exist in apple. Expression analysis indicated that transcript levels of early phenylpropanoid pathway genes in apple and pear leaves were similar, except for chalcone isomerase (CHI), which was much lower in apple. Apples also showed very low CHI activity compared with pear. To relieve the bottleneck at CHI, transgenic apple plants overexpressing the Arabidopsis AtCHI gene were produced. Unlike other transgenic apples where phenylpropanoid flux was manipulated, AtCHI overexpression (CHIox) plants were phenotypically indistinguishable from wild‐type, except for an increase in red pigmentation in expanding leaves. CHIox plants accumulated slightly increased levels of flavanols and flavan‐3‐ols in the leaves, but the major change was a 2.8‐ to 19‐fold drop in phloridzin concentrations compared with wild‐type. The impact of these phytochemical changes on insect preference was studied using a two‐choice leaf assay with the polyphagous apple pest, the two‐spotted spider mite (Tetranychus urticae Koch). Transgenic CHIox leaves were more susceptible to herbivory, an effect that could be reversed (complemented) by application of phloridzin to transgenic leaves. Taken together, these findings shed new light on phenylpropanoid biosynthesis in apple and suggest a new physiological role for phloridzin as an antifeedant in leaves.
Lability of dissolved organic carbon from boreal peatlands: interactions between permafrost thaw, wildfire, and season
Authors: Burd Katheryn , Estop-Aragonés Cristian , Tank Suzanne E. , Olefeldt David 
Published: February 2020

Boreal peatlands are major sources of dissolved organic carbon (DOC) to downstream aquatic ecosystems, where it influences carbon cycling and food web structure. Wildfire and permafrost thaw alter peatland vegetation and hydrology and may affect the quantity and chemical composition of exported DOC. We studied the influence of wildfire and thaw on microbial and photochemical lability of near-surface porewater DOC, assessed through 7 d incubations. We carried out these incubations in spring, summer, and fall but only found differences in spring when DOC biodegradability (% loss during dark incubations) increased with lower DOC aromaticity and C/N ratios. During spring, the most labile DOC was found in recently formed thermokarst bogs along collapsing peat plateau edges (25% loss), which was greater than in mature sections of thermokarst bogs (3%), and peat plateaus with intact permafrost (9%). Increased DOC lability following thaw was likely linked to high DOC production and turnover associated with productive hydrophilic Sphagnum mosses and sedges, rather than thawed permafrost peat. A wildfire (3 yr prior) reduced DOC biodegradability in both peat plateaus (4%) and rapidly collapsing peat plateau edges (14%). Biodegradability of DOC in summer and fall was low across all sites; 2% and 4%, respectively. Photodegradation was shown to potentially contribute significantly to downstream DOC degradation but did not vary across peatland sites. We show that disturbances such as permafrost thaw and wildfire have the potential to affect downstream carbon cycling, particularly as the largest influences were found in spring when peatlands are well connected to downstream aquatic ecosystems.
Digital Libraries
Authors: Manghi Paolo , Candela Leonardo , Lazzeri Emma , Silvello Gianmaria 
Published: February 2020

The Italian Research Conference on Digital Libraries (IRCDL) is the annual Italian forum to discuss research topics on Digital Libraries and related technical, practical, and social issues. Along the years, IRCDL touched several aspects underlying the ?Digital Library" domain and promptly adapted to the evolution of the field. Today, the ?Digital Library" field includes theory and practices reflecting the evolution of the role of libraries in the scholarly communication domain, and also embracing scholarly communication and open science.
The theme of IRCDL 2019 was ?Digital Libraries: Supporting Open Science". Three main reasons motivated this theme: (i) science is increasingly becoming digital, meaning that research is performed using data services and digital tools; (ii) the results of the research are no longer just traditional scientific publications; (iii) the outcomes of science are increasingly encompassing datasets, software, and experiments. As digital artifacts, such products can be shared and re-used together with the article, thus enabling comprehensive research assessment and various degrees of reproducibility of science. Positive consequences of this shift towards Open Science are: accelerating science, optimizing the cost of research, fraud detection, and fullyfledged scientific reward. Digital Libraries are central in the evolution of research outputs by targeting findability, preservation, interlinking, and re-use of research products and by integrating the components of the scholarly communication process.
The conference has been organized in Pisa, and the proceedings are published in the Springer CCIS series Vol. 988 [22]. Pre-print versions, research datasets, and research software relative to the accepted contributions are accessible via Zenodo.org.
Perineural Invasion Reprograms the Immune Microenvironment through Cholinergic Signaling in Pancreatic Ductal Adenocarcinoma
Authors: Yang Min-Wei , Tao Ling-Ye , Jiang Yong-Sheng , Yang Jian-Yu , Huo Yan-Miao , Liu De-Jun , Li Jiao , Fu Xue-Liang , He Ruizhe , Lin Chaoyi , Liu Wei , Zhang Jun-Feng , Hua Rong , Li Qing , Jiang Shu-Heng , Hu Li-Peng , Tian Guang-Ang , Zhang Xiao-Xin , Niu Ningning , Lu Ping , Shi Juanjuan , Xiao Gary G. , Wang Li-Wei , Xue Jing , Zhang Zhi-Gang , Sun Yong-Wei 
Published: February 2020

Abstract

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8+ T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion–triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T-cell infiltration and a reduced Th1/Th2 ratio.

Significance:
These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.