bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers
Authors: Huguier Vincent , Giot Jean-Philippe , Simonneau Marie , Levillain Pierre , Charreau Sandrine , Garcia Martine , Jégou Jean-François , Bodet Charles , Morel Franck , Lecron Jean-Claude , Favot Laure 
Published: February 2019

AbstractWound healing is a complex physiological process that repairs a skin lesion and produces fibrous tissue. In some cases, this process can lead to hypertrophic scars (HS) or keloid scars (KS), for which the pathophysiology remains poorly understood. Previous studies have reported the presence of oncostatin M (OSM) during the wound healing process; however, the role of OSM in pathological scarring remains to be precisely elucidated. This study aims to analyse the presence and involvement of OSM in the pathological scarring process. It was conducted with 18 patients, including 9 patients with hypertrophic scarring and 9 patients with keloid scarring. Histological tissue analysis of HS and KS showed minor differences in the organization of the extracellular matrix, the inflammatory infiltrate and the keratinocyte phenotype. Transcriptomic analysis showed increased expression levels of fibronectin, collagen I, TGFβ1, β-defensin-2 and S100A7 in both pathological samples. OSM expression levels were greater in HS than in KS and control skin. In vitro, OSM inhibited TGFβ1-induced secretion of components of the extracellular matrix by normal and pathological fibroblasts. Overall, we suggest that OSM is involved in pathological wound healing processes by inhibiting the evolution of HS towards KS by controlling the fibrotic effect of TGFβ1.
Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT)
Authors: Siddiqui Mohammad R. , Railkar Reema , Sanford Thomas , Crooks Daniel R. , Eckhaus Michael A. , Haines Diana , Choyke Peter L. , Kobayashi Hisataka , Agarwal Piyush K. 
Published: February 2019

AbstractBladder cancer (BC) is heterogeneous and expresses various cell surface targets. Photoimmunotherapy (PIT) involves monoclonal antibodies (MAbs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by near infra-red light (NIR) to specifically target tumors. We have demonstrated that tumors expressing EGFR can be targeted with PIT. However, PIT may be less effective when a tumor lacks “overwhelming” expression of a single target such as EGFR. We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Human BC tissues and cell lines were analyzed for EGFR and HER2 expression. Efficacy of PA-labeled MAbs singly and in combination was analyzed. About 45% of BC tissues stain for both EGFR and HER2. In vitro, the combination of pan IR700 and tra IR700 with NIR was more efficacious than either agent alone. Tumor xenografts treated with combination PIT showed significant tumor growth retardation. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors.
Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents
Authors: He Fan , Berg Arthur , Imamura Kawasawa Yuka , Bixler Edward O. , Fernandez-Mendoza Julio , Whitsel Eric A. , Liao Duanping 
Published: February 2019

AbstractChildhood obesity remains an epidemic in the U.S. and worldwide. However, little is understood regarding the epigenetic basis of obesity in adolescents. To investigate the cross-sectional association between DNA methylation level in obesity-related genes and body mass index (BMI) percentile, data from 263 adolescents in the population-based Penn State Child Cohort follow-up exam was analysed. Using DNA extracted from peripheral leukocytes, epigenome-wide single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions was obtained. We used multivariable-adjusted linear regression models to assess the association between site-specific methylation level and age- and sex-specific BMI percentile. Hypergeometric and permutation tests were used to determine if obesity-related genes were significantly enriched among all intragenic sites that achieved a p < 0.05 throughout the epigenome. Among the 5,669 sites related to BMI percentile with p < 0.05, 28 were identified within obesity-related genes. Obesity-related genes were significantly enriched among 103,466 intragenic sites (Phypergeometric = 0.006; Ppermutation = 0.006). Moreover, increased methylation on one site within SIM1 was significantly related to higher BMI percentile (P = 4.2E-05). If externally validated, our data would suggest that DNA methylation in obesity-related genes may relate to obesity risk in adolescents.
Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma
Authors: Misra Sougat , Moro Carlos F. , Del Chiaro Marco , Pouso Soledad , Sebestyén Anna , Löhr Matthias , Björnstedt Mikael , Verbeke Caroline S. 
Published: February 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, which is mainly due to late diagnosis and profound resistance to treatment. The latter is to a large extent attributed to the tumor stroma that is exceedingly prominent in PDAC and engages in complex interactions with the cancer cells. Hence, relevant preclinical models of PDAC should also include the tumor stroma. We herein describe the establishment and functional validation of an ex vivo organotypic culture of human PDAC that is based on precision-cut tissue slices from surgical specimens and reproducibly recapitulates the complex cellular and acellular composition of PDAC, including its microenvironment. The cancer cells, tumor microenvironment and interspersed remnants of nonneoplastic pancreas contained in these 350 µm thick slices maintained their structural integrity, phenotypic characteristics and functional activity when in culture for at least 4 days. In particular, tumor cell proliferation persisted and the grade of differentiation and morphological phenotype remained unaltered. Cultured tissue slices were metabolically active and responsive to rapamycin, an mTOR inhibitor. This culture system is to date the closest surrogate to the parent carcinoma and harbors great potential as a drug sensitivity testing system for the personalized treatment of PDAC.
The long non-coding RNA Meg3 is dispensable for hematopoietic stem cells
Authors: Sommerkamp Pia , Renders Simon , Ladel Luisa , Hotz-Wagenblatt Agnes , Schönberger Katharina , Zeisberger Petra , Przybylla Adriana , Sohn Markus , Zhou Yunli , Klibanski Anne , Cabezas-Wallscheid Nina , Trumpp Andreas 
Published: February 2019

AbstractThe long non-coding RNA (lncRNA) Maternally Expressed Gene 3 (Meg3) is encoded within the imprinted Dlk1-Meg3 gene locus and is only maternally expressed. Meg3 has been shown to play an important role in the regulation of cellular proliferation and functions as a tumor suppressor in numerous tissues. Meg3 is highly expressed in mouse adult hematopoietic stem cells (HSCs) and strongly down-regulated in early progenitors. To address its functional role in HSCs, we used MxCre to conditionally delete Meg3 in the adult bone marrow of Meg3mat-flox/pat-wt mice. We performed extensive in vitro and in vivo analyses of mice carrying a Meg3 deficient blood system, but neither observed impaired hematopoiesis during homeostatic conditions nor upon serial transplantation. Furthermore, we analyzed VavCre Meg3mat-flox/pat-wt mice, in which Meg3 was deleted in the embryonic hematopoietic system and unexpectedly this did neither generate any hematopoietic defects. In response to interferon-mediated stimulation, Meg3 deficient adult HSCs responded highly similar compared to controls. Taken together, we report the finding, that the highly expressed imprinted lncRNA Meg3 is dispensable for the function of HSCs during homeostasis and in response to stress mediators as well as for serial reconstitution of the blood system in vivo.
A Monte Carlo feasibility study for neutron based real-time range verification in proton therapy
Authors: Ytre-Hauge Kristian Smeland , Skjerdal Kyrre , Mattingly John , Meric Ilker 
Published: February 2019

AbstractUncertainties in the proton range in tissue during proton therapy limit the precision in treatment delivery. These uncertainties result in expanded treatment margins, thereby increasing radiation dose to healthy tissue. Real-time range verification techniques aim to reduce these uncertainties in order to take full advantage of the finite range of the primary protons. In this paper, we propose a novel concept for real-time range verification based on detection of secondary neutrons produced in nuclear interactions during proton therapy. The proposed detector concept is simple; consisting of a hydrogen-rich converter material followed by two charged particle tracking detectors, mimicking a proton recoil telescopic arrangement. Neutrons incident on the converter material are converted into protons through elastic and inelastic (n,p) interactions. The protons are subsequently detected in the tracking detectors. The information on the direction and position of these protons is then utilized in a new reconstruction algorithm to estimate the depth distribution of neutron production by the proton beam, which in turn is correlated with the primary proton range. In this paper, we present the results of a Monte Carlo feasibility study and show that the proposed concept could be used for real-time range verification with millimetric precision in proton therapy.
Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
Authors: Alieva Maria , Leidgens Verena , Riemenschneider Markus J. , Klein Christoph A. , Hau Peter , van Rheenen Jacco 
Published: February 2019

AbstractThe pathogenesis of glioblastoma (GBM) is characterized by highly invasive behavior allowing dissemination and progression. A conclusive image of the invasive process is not available. The aim of this work was to study invasion dynamics in GBM using an innovative in vivo imaging approach. Primary brain tumor initiating cell lines from IDH-wild type GBM stably expressing H2B-Dendra2 were implanted orthotopically in the brains of SCID mice. Using high-resolution time-lapse intravital imaging, tumor cell migration in the tumor core, border and invasive front was recorded. Tumor cell dynamics at different border configurations were analyzed and multivariate linear modelling of tumor cell spreading was performed. We found tumor border configurations, recapitulating human tumor border morphologies. Not only tumor borders but also the tumor core was composed of highly dynamic cells, with no clear correlation to the ability to spread into the brain. Two types of border configurations contributed to tumor cell spreading through distinct invasion patterns: an invasive margin that executes slow but directed invasion, and a diffuse infiltration margin with fast but less directed movement. By providing a more detailed view on glioma invasion patterns, our study may improve accuracy of prognosis and serve as a basis for personalized therapeutic approaches.
Exquisitely-preserved, high-definition skin traces in diminutive theropod tracks from the Cretaceous of Korea
Authors: Kim Kyung Soo , Lockley Martin G. , Lim Jong Deock , Xing Lida 
Published: February 2019

AbstractSmall theropod tracks, ichnogenus Minisauripus, from the Jinju Formation (Cretaceous) of Korea reveal exquisitely preserved skin texture impressions. This is the first report for any dinosaur of skin traces that cover entire footprints, and every footprint in a trackway. Special sedimentological conditions allowed footprint registration without smearing of skin texture patterns which consist of densely-packed, reticulate arrays of small (<0.5 mm) polygons, preserved as both impressions and casts, the latter essentially foot replicas. The skin texture resembles that reported for two Lower Cretaceous avian theropods (birds) from China which had quite different foot morphologies. This is also the oldest report of Minisauripus from Korea predating five reports from the Haman Formation of inferred Albian age. Minisauripus is now known from six Korean and three Chinese localities, all from the Lower Cretaceous. This gives a total sample of ~95 tracks representing ~54 trackways. With >80% of tracks <3.0 cm long, Minisauripus is pivotal in debates over whether small tracks represent small species, as the database suggests, or juveniles of large species.
Annual change in FEV1 in elderly 10-year survivors with established chronic obstructive pulmonary disease
Authors: Suzuki Masaru , Makita Hironi , Konno Satoshi , Shimizu Kaoruko , Nasuhara Yasuyuki , Nagai Katsura , Akiyama Yasushi , Fuke Satoshi , Saito Hiroshi , Igarashi Takeshi , Takeyabu Kimihiro , Nishimura Masaharu 
Published: February 2019

AbstractLong-term decline in lung function is generally considered to be progressive in individuals with established chronic obstructive pulmonary disease (COPD), despite the presence of intersubject variation. We hypothesized that the annualized rate of decline in forced expiratory volume in 1 second (FEV1) would not be constant among different time periods in the natural history of established COPD. We compared the annual change rates in FEV1 during the first 5 years and the last 5 years, estimated separately using a linear mixed-effects model in 10-year survivors (n = 110). The subjects were classified into three FEV1 decline groups, based on the 25th and 75th percentile values in each time period. The rates of FEV1 changes, calculated from the first 5 years and the last 5 years, did not correlate with each other among 10-year survivors; the subjects of each FEV1 decline group during the first 5 years did not consistently remain in the same FEV1 decline group during the last 5 years. Smoking status and exacerbation frequency were not associated with decline in FEV1. In conclusion, the disease activity, which is often expressed as annualized change in FEV1, might be changeable either way over years in patients with established COPD.
Stress-induced mast cell activation contributes to atherosclerotic plaque destabilization
Authors: Lagraauw H. Maxime , Wezel Anouk , van der Velden Daniël , Kuiper Johan , Bot Ilze 
Published: February 2019

AbstractMast cells accumulate in the perivascular tissue during atherosclerotic plaque progression and contribute to plaque destabilization. However, the specific triggers for mast cell activation in atherosclerosis remain unresolved. We hypothesized that psychological stress-induced activation of mast cells may contribute to plaque destabilization. To investigate this, apoE−/− mice on Western-type diet were exposed to 120′ restraint stress. A single episode of restraint caused a significant increase in mast cell activation in the heart. In addition to a rise in serum corticosterone and changes in circulating leukocyte populations, we observed an increase in the circulating pro-inflammatory cytokine interleukin (IL)-6 in the stressed mice. Subsequent characterization of the atherosclerotic plaques revealed a high incidence and larger size of intraplaque hemorrhages in stressed mice. In mast cell-deficient apoE−/− mice, restraint stress affected circulating leukocyte levels, but did not increase plasma IL-6 levels. Furthermore, we did not observe any intraplaque hemorrhages in these mice upon stress, strongly indicating the involvement of a mast cell-dependent response to stress in atherosclerotic plaque destabilization. In conclusion, we demonstrate that acute stress activates mast cells, which induces the incidence of intraplaque hemorrhage in vivo, identifying acute stress as a risk factor for atherosclerotic plaque destabilization.
Unexpected population fragmentation in an endangered seabird: the case of the Peruvian diving-petrel
Authors: Cristofari Robin , Plaza Paula , Fernández Claudia E. , Trucchi Emiliano , Gouin Nicolas , Le Bohec Céline , Zavalaga Carlos , Alfaro-Shigueto Joanna , Luna-Jorquera Guillermo 
Published: February 2019

AbstractIn less than one century, the once-abundant Peruvian diving petrel has become the first endangered seabird of the Humboldt Current System (HCS). This small endemic petrel of the South American Pacific coast is now an important indicator of ongoing habitat loss and of the success of local conservation policies in the HCS - an ecoregion designated as a priority for the conservation of global biodiversity. Yet so far, poorly understood life history traits such as philopatry or dispersal ability may strongly influence the species’ response to ecosystem changes, but also our capacity to assess and interpret this response. To address this question, we explore the range-wide population structure of the Peruvian diving petrel, and show that this small seabird exhibits extreme philopatric behavior at the island level. Mitochondrial DNA sequences and genome-wide SNP data reveal significant isolation and low migration at very short distances, and provide strong evidence for questioning the alleged recovery in the Peruvian and Chilean populations of this species. Importantly, the full demographic independence between colonies makes local population rescue through migration unlikely. As a consequence, the Peruvian diving petrel appears to be particularly vulnerable to ongoing anthropogenic pressure. By excluding immigration as a major factor of demographic recovery, our results highlight the unambiguously positive impact of local conservation measures on breeding populations; yet at the same time they also cast doubt on alleged range-wide positive population trends. Overall, the protection of independent breeding colonies, and not only of the species as a whole, remains a major element in the conservation strategy for endemic seabirds. Finally, we underline the importance of considering the philopatric behavior and demographic independence of breeding populations, even at very fine spatial scales, in spatial planning for marine coastal areas.
Unexpected rip currents induced by a meteotsunami
Authors: Linares Álvaro , Wu Chin H. , Bechle Adam J. , Anderson Eric J. , Kristovich David A. R. 
Published: February 2019

AbstractA tragic drowning event occurred along southeastern beaches of Lake Michigan on a sunny and calm July 4, 2003, hours after a fast-moving convective storm had crossed the lake. Data forensics indicates that a moderate-height (~0.3 m) meteotsunami was generated by the fast-moving storm impacting the eastern coast of the lake. Detailed Nearshore Area (DNA) modeling forensics on a high-resolution spatial O(1 m) grid reveals that the meteotsunami wave generated unexpected rip currents, changing the nearshore condition from calm to hazardous in just a few minutes and lasting for several hours after the storm. Cross-comparison of rip current incidents and meteotsunami occurrence databases suggests that meteotsunamis present severe water safety hazards and high risks, more frequently than previously recognized. Overall, meteorological tsunamis are revealed as a new generation mechanism of rip currents, thus posing an unexpected beach hazard that, to date, has been ignored.
Seroprevalence of six pathogens transmitted by the Ixodes ricinus ticks in asymptomatic individuals with HIV infection and in blood donors
Authors: Pawełczyk Agnieszka , Bednarska Małgorzata , Kowalska Justyna D. , Uszyńska-Kałuża Beata , Radkowski Marek , Welc-Falęciak Renata 
Published: February 2019

AbstractThe objective of our study was to estimate the seroprevalence of six pathogens transmitted by ticks in HIV-infected persons and blood donors in Poland (B.burgdorferis.l.,A.phagocytophilum,Ehrlichiaspp.,Babesiaspp.,Rickettsiaspp.Bartonella henselae) to assess the frequency of exposure to such microorganisms in immunocompetent and immunocompromised individuals in endemic regions forI.ricinusticks. Serum samples were collected from 227 HIV-infected patients and 199 blood donors. All samples were analyzed for antibodies against six tick-borne pathogens and seroprevalence rates were statistically compared between two tested group as well as age, sex and lymphocyte T CD4+ level in HIV infected patients. The seroprevalence of tick-borne infections in HIV-infected patients is higher than that of the healthy population in Poland, although no association between serological status of patients and lymphocyte CD4+ T cell level has been observed. The frequency of tick-borne coinfections and doubtful results of serological tests were significantly higher in HIV-positive individuals. In Poland, the possibility of tick-borne diseases transmission with blood is rather negligible.
Curcumin and Quercetin as Potential Radioprotectors and/or Radiosensitizers for X-ray-based Sterilization of Male Navel Orangeworm Larvae
Authors: Liang Pei-Shih , Haff Ronald P. , Ovchinnikova Inna , Light Douglas M. , Mahoney Noreen E. , Kim Jong H. 
Published: February 2019

AbstractTwo natural compounds (quercetin and curcumin) were tested as sensitizing or protecting agents for Navel Orangeworm (NOW) larvae under x-ray sterilization, with the aim to reduce required doses and thus facilitate the substitution of x-ray for radioisotopes. The compounds were added to NOW diet at concentrations between 0 and 1.0 mmol kg−1 and subsequent reared male larvae were subjected to x-ray irradiation (90 keV, 9 mA) to doses up to 15 Gy. Upon emergence as adults, surviving male NOW were paired with colony virgin females and placed in isolation for observation of deformity, mortality, and fertility. Treatments included rearing larvae on infused diet before irradiation, after irradiation, and both. Results were tabulated as percentage of insects that were dead/deformed, infertile, or fertile and subjected to chi-squared analysis. While insect populations subjected to quercetin treatments were not found to be significantly different from control at any x-ray dose, all curcumin treatments yielded significant differences at an absorbed dose of 10 Gy, both in terms of decreased mortality and fertility. While none of the treatments resulted in acceptable mortality/deformity rates, the observed effects strongly support the need for continued testing of natural compounds for their efficacy to reduce required dose levels for sterilization.