bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWS‐FLI1 regulates a transcriptional program in cooperation with Foxq1 in mouse Ewing sarcoma
Authors: Shimizu Rikuka , Tanaka Miwa , Tsutsumi Shuichi , Aburatani Hiroyuki , Yamazaki Yukari , Homme Mizuki , Kitagawa Yoshimasa , Nakamura Takuro 
Published: June 2018

EWS‐FLI1 constitutes an oncogenic transcription factor that plays key roles in Ewing sarcoma development and maintenance. We have recently succeeded in generating an ex vivo mouse model for Ewing sarcoma by introducing EWS‐FLI1 into embryonic osteochondrogenic progenitors. The model well recapitulates the biological characteristics, small round cell morphology, and gene expression profiles of human Ewing sarcoma. Here, we clarified the global DNA binding properties of EWS‐FLI1 in mouse Ewing sarcoma. GGAA microsatellites were found to serve as binding sites of EWS‐FLI1 albeit with less frequency than that in human Ewing sarcoma; moreover, genomic distribution was not conserved between human and mouse. Nevertheless, EWS‐FLI1 binding sites within GGAA microsatellites were frequently associated with the histone H3K27Ac enhancer mark, suggesting that EWS‐FLI1 could affect global gene expression by binding its target sites. In particular, the Fox transcription factor binding motif was frequently observed within EWS‐FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS‐FLI1. Trib1 and Nrg1 were demonstrated as target genes that are co‐regulated by EWS‐FLI1 and Foxq1, and are important for cell proliferation and survival of Ewing sarcoma. Collectively, our findings present novel aspects of EWS‐FLI1 function as well as the importance of GGAA microsatellites.
Meta‐analysis of the effects of rice‐field abandonment on biodiversity in Japan
Authors: Koshida Chieko , Katayama Naoki 
Published: June 2018

AbstractFarmland abandonment is increasing worldwide. Concurrently, some conservationists view this as an opportunity for biodiversity restoration (i.e., rewilding). Due to a lack of data, however, it remains unclear whether farmland abandonment increases biodiversity in different farmland types and surrounding environments. Information is particularly scarce for Asia, home to one‐third of identified biodiversity hotspots and where dominant farmlands (i.e., rice fields) are often viewed as substitutes for natural wetlands. We conducted the first meta‐analysis of the impacts of rice‐field abandonment on biodiversity, in which we considered multiscale factors, such as taxon surveyed, landscape context, and climate. Species richness and abundance after abandonment decreased to 56–72%. This reduced biodiversity was unlikely to recover, at least for plant species richness, even after 10–15 years. These results suggest rewilding will not necessarily be achieved by rice‐field abandonment. Moreover, there was a pronounced biodiversity decline under dry conditions (e.g., low precipitation), especially for organisms closely associated with aquatic environment, such as amphibians and fish. Biodiversity reduction was least pronounced for birds and mammals. Such context dependency may suggest that impacts of farmland abandonment can be predicted by considering biological features of organisms and their associations with human‐modified environments.
Chronic hand eczema: A prospective analysis of the Swiss CARPE registry focusing on factors associated with clinical and quality of life improvement
Authors: Cazzaniga Simone , Ballmer‐Weber Barbara K. , Gräni Nora , Spring Philippe , Bircher Andreas , Anliker Mark , Sonntag Anne‐Katharina , Piletta Pierre , Huber Caroline , Diepgen Thomas L. , Apfelbacher Christian , Naldi Luigi , Borradori Luca , Simon Dagmar 
Published: June 2018

BackgroundHand eczema (HE) is common and may follow a chronic disease course. So far, prospective studies investigating the risk factors for disease progression as a prerequisite for targeted prevention are scarce.ObjectiveTo evaluate the overall association of HE‐associated factors with clinical and quality of life (QoL) improvement during a follow‐up of 2 years.MethodsData of the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE) registry on long‐term patient management (CARPE‐CH) were analysed by means of both classic regression and semantic map analyses.ResultsBoth severity of HE and QoL significantly improved over the period of 2 years (P < .001). However, 20% of patients had moderate to severe HE after 2 years of follow‐up. As factors associated with an unfavourable CHE clinical course and QoL, environmental exposures, male sex, occupational skin disease, job loss or change at baseline, allergic contact dermatitis, a chronic disease course, palmar localization and widespread eczema were identified.ConclusionsAnalysis of prospective data from CARPE‐CH shows a complex pattern of associations among variables as shown by semantic map and classic statistical analyses. Factors related to occupational exposure had the highest impact on CHE.
Regulation of contact sensitivity in non‐obese diabetic (NOD) mice by innate immunity
Authors: Szczepanik Marian , Majewska‐Szczepanik Monika , Wong Florence S. , Kowalczyk Paulina , Pasare Chandrashekhar , Wen Li 
Published: June 2018

BackgroundGenetic background influences allergic immune responses to environmental stimuli. Non‐obese diabetic (NOD) mice are highly susceptible to environmental stimuli. Little is known about the interaction of autoimmune genetic factors with innate immunity in allergies, especially skin hypersensitivity.ObjectivesTo study the interplay of innate immunity and autoimmune genetic factors in contact hypersensitivity (CHS) by using various innate immunity‐deficient NOD mice.MethodsToll‐like receptor (TLR) 2‐deficient, TLR9‐deficient and MyD88‐deficient NOD mice were used to investigate CHS. The cellular mechanism was determined by flow cytometry in vitro and adoptive cell transfer in vivo. To investigate the role of MyD88 in dendritic cells (DCs) in CHS, we also used CD11cMyD88+ MyD88−/− NOD mice, in which MyD88 is expressed only in CD11c+ cells.ResultsWe found that innate immunity negatively regulates CHS, as innate immunity‐deficient NOD mice developed exacerbated CHS accompanied by increased numbers of skin‐migrating CD11c+ DCs expressing higher levels of major histocompatibility complex II and CD80. Moreover, MyD88−/− NOD mice had increased numbers of CD11c+ CD207− CD103+ DCs and activated T effector cells in the skin‐draining lymph nodes. Strikingly, re‐expression of MyD88 in CD11c+ DCs (CD11cMyD88+ MyD88−/− NOD mice) restored hyper‐CHS to a normal level in MyD88−/− NOD mice.ConclusionOur results suggest that the autoimmune‐prone NOD genetic background aggravates CHS regulated by innate immunity, through DCs and T effector cells.
MART‐1‐labeled melanocyte density and distribution in actinic keratosis and squamous cell cancer in situ: Pagetoid melanocytes are a potential source of misdiagnosis as melanoma in situ
Authors: Fix William C. , Yun Sook Jung , Groft MacFarlane Caroline M. , Jambusaria Anokhi , Elenitsas Rosalie , Chu Emily , Etzkorn Jeremy R. , Sobanko Joseph F. , Shin Thuzar M. , Miller Christopher J. 
Published: June 2018

BackgroundActinic keratosis (AK) and squamous cell carcinoma in‐situ (SCCIS) within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping clinical and microscopic features. This study aimed to describe basilar melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic accuracy.MethodsA total of 22 AK and 22 SCCIS biopsies containing a margin of uninvolved epidermis were immunostained with MART‐1 (melanoma antigen recognized by T‐cells 1). The basilar melanocyte:keratinocyte ratio and the number and distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved epidermis. An in‐vitro human skin model was created to assess the impact of keratinocyte atypia on melanocyte distribution.ResultsThe median basilar melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P < 0.0001). Pagetoid melanocytes at or above the mid‐spinous layer were more common in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in the in‐vitro skin model made with neoplastic but not normal keratinocytes.ConclusionsPagetoid melanocytes in AK and SCCIS should be interpreted with caution to avoid overdiagnosis of MIS.
Endoscopic papillary large balloon dilation and endoscopic papillary balloon dilation both without sphincterotomy for removal of large bile duct stones: A propensity‐matched analysis
Authors: Hakuta Ryunosuke , Kawahata Shuhei , Kogure Hirofumi , Nakai Yousuke , Saito Kei , Saito Tomotaka , Hamada Tsuyoshi , Takahara Naminatsu , Uchino Rie , Mizuno Suguru , Tsujino Takeshi , Tada Minoru , Sakamoto Naoya , Isayama Hiroyuki , Koike Kazuhiko 
Published: June 2018

Background and AimEndoscopic papillary large balloon dilation (EPLBD) without endoscopic sphincterotomy (EST) may facilitate extraction of large bile duct stones through achieving adequate dilation of the ampulla. However, contrary to favorable long‐term outcomes after endoscopic papillary balloon dilation (EPBD), that of EPLBD without EST has been little investigated. Therefore, we conducted the current study to evaluate short‐ and long‐term outcomes of EPLBD without EST and EPBD after removal of large bile duct stones (LBDS; ≥10 mm).MethodsThis retrospective study included patients without a previous history of EST, EPBD or EPLBD who underwent EPLBD without EST or EPBD for removal of LBDS. Each patient in the EPLBD without EST group was matched to a patient in the EPBD group using propensity scores.ResultsForty‐four patients in each group were matched for the analysis. Baseline characteristics were balanced after propensity matching. Rate of complete stone removal in a single session was higher (80% vs 16%, P < 0.001), number of ERCP sessions (1.3 ± 0.7 vs 2.4 ± 1.5, P < 0.001) and rate of lithotripsy use (30% vs 80%, P < 0.001) were smaller in the matched EPLBD without EST group. Contrary to null between‐group differences in early adverse events (P = 0.99), a cumulative rate of late biliary complications was higher in the EPLBD without EST group (P = 0.02).ConclusionEPLBD without EST showed higher efficacy for removal of LBDS but was associated with worse long‐term outcomes when compared to EPBD.
Beamforming algorithms for endocardial border detection
Authors: Kulina Robert , Seetharam Karthik , Agarwal Sunil , Wiley Brandon M. , Narula Jagat , Chaudhry Farooq A. , Sengupta Partho P. 
Published: June 2018

BackgroundSoftware‐based beamforming which utilizes delay and standard beamforming is a signal processing technique that temporarily stores data from each probe element to improve specular reflections to improve the image resolution. We compared a software algorithm which uses delay and standard beamforming with delay and sum beamforming in standard, hardware to evaluate endocardial borders and need for echo contrast.MethodsIn this prospective study, eligible participants were ≥18 years of age referred clinically for transthoracic echocardiograms. A limited study consisting of three views (apical 4, apical 3, and apical 2 chamber) was performed with the software‐based beamforming and standard platform. Number and quality of segments visualized were evaluated using a 17‐segment model. Quality of segments was graded as 0 = not visualized, 1 = incompletely visualized, or 2 = completely visualized. Overall quality score for each study (0 = poor, 1 = adequate, 2 = good) was reported. The need for contrast was determined by ASE guidelines.ResultsA total of 101 patients (mean age 61 ± 16 years, males 52%) were enrolled. Mean number of segments visualized in apical 4‐ (6.28 vs 5.65, P < .001), apical 3‐ (6.27 vs 5.54, P < .001), and apical 2‐chamber views (6.26 vs 5.72 P < .001) was higher with the software vs standard platform. The average overall score for image quality was significantly better for the software platform vs standard (1.4 vs 0.9, P =< .001). With the software platform, 23% were judged as requiring contrast as compared with 45% for the standard platform (P < .001).ConclusionsDelay and standard beamforming in software platform identified more segments with better image quality when compared to the standard high‐end platform, decreasing the need for contrast usage.
Deciphering the mechanism of potent peptidomimetic inhibitors targeting plasmepsins – biochemical and structural insights
Authors: Mishra Vandana , Rathore Ishan , Arekar Anagha , Sthanam Lakshmi Kavitha , Xiao Huogen , Kiso Yoshiaki , Sen Shamik , Patankar Swati , Gustchina Alla , Hidaka Koushi , Wlodawer Alexander , Yada Rickey Y. , Bhaumik Prasenjit 
Published: June 2018

Malaria is a deadly disease killing worldwide hundreds of thousands people each year and the responsible parasite has acquired resistance to the available drug combinations. The four vacuolar plasmepsins (PMs) in Plasmodium falciparum involved in hemoglobin (Hb) catabolism represent promising targets to combat drug resistance. High antimalarial activities can be achieved by developing a single drug that would simultaneously target all the vacuolar PMs. We have demonstrated for the first time the use of soluble recombinant plasmepsin II (PMII) for structure‐guided drug discovery with KNI inhibitors. Compounds used in this study (KNI‐10742, 10743, 10395, 10333, and 10343) exhibit nanomolar inhibition against PMII and are also effective in blocking the activities of PMI and PMIV with the low nanomolar Ki values. The high‐resolution crystal structures of PMII–KNI inhibitor complexes reveal interesting features modulating their differential potency. Important individual characteristics of the inhibitors and their importance for potency have been established. The alkylamino analog, KNI‐10743, shows intrinsic flexibility at the P2 position that potentiates its interactions with Asp132, Leu133, and Ser134. The phenylacetyl tripeptides, KNI‐10333 and KNI‐10343, accommodate different ρ‐substituents at the P3 phenylacetyl ring that determine the orientation of the ring, thus creating novel hydrogen‐bonding contacts. KNI‐10743 and KNI‐10333 possess significant antimalarial activity, block Hb degradation inside the food vacuole, and show no cytotoxicity on human cells; thus, they can be considered as promising candidates for further optimization. Based on our structural data, novel KNI derivatives with improved antimalarial activity could be designed for potential clinical use.DatabaseStructural data are available in the PDB under the accession numbers 5YIE, 5YIB, 5YID, 5YIC, and 5YIA.
Influence of radiation on Hemarthria compressa's genetic variations
Authors: Wu Bingchao , Zhang Yu , Yan Haidong , Yang Shengting , Zhou Sifan , Zhang Xinquan , Liu Wei , Nie Gang , Peng Yan , Ma Xiao , Yan Yanhong , Li Zhou , Huang Linkai 
Published: June 2018

AbstractUsing the material of Hemarthria compressa (L.F.) R.Br. cv. YA’AN, we carried out this research to study the influence of radiation on the genetic variation of plants. Genetic difference was analyzed with expressed sequence tag‐simple sequence repeat (EST‐SSR) molecular marker through the comparison of 60Co‐γ radiation on H. compressa seed stems and original variety. By using 20 primer pairs, 176 polymerase chain reaction (PCR)‐amplifications with clear and consistent bands were obtained. The results showed that 155 of 176 bands were polymorphic, which indicating an 88.07% polymorphism rate, and each pair of primers had 8.8 amplified bands on average; the amplitude of polymorphism information content was 0.4709–0.6952 with an average value 0.6081. The genetic similarity coefficient of H. compressa and its mutants ranged from 0.4318 to 0.8239 with an average of 0.6671. As a consequence, existence of genetic differences between the mutants and the basic material was proved.
In the shadows of empires: Early medieval Croatia in the ninth and tenth centuries
Authors: Majnarić Ivan 
Published: June 2018

AbstractThe early medieval history of the European periphery in the 9th century and its relations with the Carolingian and the Byzantine Empire have in the last two decades become a focal point for medievalists. In a number of research papers studying the areas beyond the eastern borders of the Carolingian Empire, interest has been shown for the northeastern hinterlands of the Adriatic coast, that is, the area in which the Duchy of Croatia was formed during the 9th century. The question at the heart of these medievalists' interest is the appearance of Croats in recorded history. The modern solutions to this question are not unanimous, as they range from a collective migration in the 7th century to the creation of a Croatian elite in the first half of the 10th. Also, due to the lack of primary sources, various methodological templates have been used to make sense of the past, applied chiefly—until recently—by non‐Croatian historians. Meanwhile, the developmental perspective of the 9th century has often been disregarded due to the ever‐present fragmentation of research—especially regarding the interrelated shaping of social and identity structures during the Carolingian and post‐Carolingian era—although this has proven essential as a means of historical inquiry when primary sources are scarce. The formation and survival of structures in early medieval Croatia during the 9th and 10th centuries should be considered in terms of the long‐term binarity of identities at the juncture of the Carolingian and the Byzantine Empire, as this paper will attempt to do.
Mesenteric tumour deposits arising from small‐intestine neuroendocrine tumours are frequently associated with fibrosis and IgG4‐expressing plasma cells
Authors: Roberts Jordan , Gonzalez Raul S , Revetta Frank , Shi Chanjuan 
Published: June 2018

AimsMesenteric tumour deposits frequently occur in small‐intestine neuroendocrine tumours. In many instances, these mesenteric tumour deposits are surrounded by a dense fibrotic stroma and have associated lymphoplasmacytic inflammation. The aim of this study was to examine whether mesenteric tumour deposits in patients with small‐intestine NETs neuroendocrine tumours show histological and immunophenotypic overlap with IgG4‐related sclerosing mesenteritis.Methods and resultsSixty‐six mesenteric tumour deposits from 66 patients with small‐intestine neuroendocrine tumours with blocks available for further studies were identified from our archives. Cases were assessed for clinicopathological features and the presence of IgG4‐positive and IgG‐positive plasma cells by immunohistochemistry. Ratios of IgG4‐positive to IgG‐positive plasma cells were calculated. Seventeen mesenteric tumour deposits (26%) showed >40 IgG4‐positive plasma cells per high‐power field, and the majority of cases (68%) showed at least some staining of IgG4‐positive plasma cells. Mesenteric tumour deposits with >20 IgG4‐positive plasma cells per high‐power field tended to be larger (25.9 ± 13.0 mm versus 18.6 ± 15.8 mm; P = 0.07), and had more IgG‐positive plasma cells (88 ± 24 versus 36 ± 37; P < 0.01) and a higher IgG4‐positive/IgG‐positive plasma cell ratio (0.66 ± 0.18 versus 0.17 ± 0.25; P < 0.01). All but one mesenteric tumour deposit with >20 IgG4‐positve plasma cells had a ratio of >40%.ConclusionsIgG4 expression is frequent in mesenteric tumour deposits from small‐intestine neuroendocrine tumours. Undersampling of tumour on biopsies of mesenteric tumour deposits could potentially cause diagnostic confusion with IgG4‐related sclerosing mesenteritis.
Are fine‐needle aspiration biopsy‐derived cell blocks a useful surrogate for tissue samples in breast cancer?
Authors: Puccetti Maurizio , Ravaioli Sara , Tumedei Maria M , Bucchi Elisa , Malmesi Manuela , Medri Laura , Bravaccini Sara 
Published: June 2018

AimsThe diagnosis of breast cancer (BC) is based on clinical examination in combination with imaging, and confirmed by pathological assessment of core needle biopsy or fine‐needle aspiration biopsy (FNAB). The biological profile of the lesion is needed to define the prognosis and establish therapy. Given the importance of an early and minimally invasive diagnosis, we aimed to verify whether the biological features detected in FNAB‐derived cytological material reflect the biological characteristics of surgical samples.Methods and resultsWe used immunohistochemistry and fluorescence in‐situ hybridisation to study a panel of conventional biomarkers [oestrogen receptor (ER), progesterone receptor (PgR), Ki67, and human epidermal growth factor receptor 2 (HER2)] in FNAB‐derived cytological samples included in cell blocks of 93 BC patients, and compared the results with those obtained from histological evaluation of the same parameters in surgical samples. Median immunopositive values of ER, PgR and Ki67 were similar in cell blocks and surgical samples. The concordance rates of ER and PgR between FNAB‐derived cell blocks and histological samples were 98% and 84%, respectively. The concordance rates of Ki67 and HER2 between the two sample types were 90% and 96%, respectively. Tumour subtype classification for triple‐negative and HER2‐positive BCs in FNAB‐derived cell blocks was always concordant with the subtype determined in surgical material.ConclusionsWe demonstrated that biological marker determination in FNAB‐derived cell blocks is feasible, and provides useful information and comparable results to those obtained with histological evaluation. Given the low cost of the procedure and its minimal impact on patients, we believe that cytological samples could be used as an alternative to tissue samples for early BC biomarker evaluation.
TESTING FOR MICRO‐EFFICIENCY IN THE HOUSING MARKET
Authors: Anundsen André Kallåk , Røed Larsen Erling 
Published: June 2018

AbstractUsing highly granular transaction‐level data for the Norwegian housing market over the period 2002–2014, we investigate whether excessive prices persist or revert in repeat sales. Excessiveness in prices is detected by comparing selling prices to predicted prices implied by a hedonic model, which includes a rich set of attributes. Persistence is rejected and there is substantial reversion in excessive prices. Our results also show little scope for profitable arbitrage by investing in apparently underpriced units. We suggest that excessive prices are related to the stochastic arrival of interested purchasers at public showings, which we show is nonrepeatable.
Immunoglobulin gene analysis as a tool for investigating human immune responses
Authors: Dunn‐Walters Deborah , Townsend Catherine , Sinclair Emma , Stewart Alex 
Published: June 2018

SummaryThe human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self‐reactive B cells removed. Later antigen‐dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation. The effector mechanism of the antibody is also adjusted, by switching the class of the antibody from IgM to one of seven other classes depending on the required function. There are many instances in human biology where positive and negative selection forces can act to shape the immunoglobulin repertoire and therefore repertoire analysis can provide useful information on infection control, vaccination efficacy, autoimmune diseases, and cancer. It can also be used to identify antigen‐specific sequences that may be of use in therapeutics. The juxtaposition of lymphocyte development and numerical evaluation of immune repertoires has resulted in the growth of a new sub‐speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.