bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma
Authors: Saengwimol Duangporn , Rojanaporn Duangnate , Chaitankar Vijender , Chittavanich Pamorn , Aroonroch Rangsima , Boontawon Tatpong , Thammachote Weerin , Jinawath Natini , Hongeng Suradej , Kaewkhaw Rossukon 
Published: October 2018

AbstractPersistent or recurrent retinoblastoma (RB) is associated with the presence of vitreous or/and subretinal seeds in advanced RB and represents a major cause of therapeutic failure. This necessitates the development of novel therapies and thus requires a model of advanced RB for testing candidate therapeutics. To this aim, we established and characterized a three-dimensional, self-organizing organoid model derived from chemotherapy-naïve tumors. The responses of organoids to drugs were determined and compared to relate organoid model to advanced RB, in terms of drug sensitivities. We found that organoids had histological features resembling retinal tumors and seeds and retained DNA copy-number alterations as well as gene and protein expression of the parental tissue. Cone signal circuitry (M/L+ cells) and glial tumor microenvironment (GFAP+ cells) were primarily present in organoids. Topotecan alone or the combined drug regimen of topotecan and melphalan effectively targeted proliferative tumor cones (RXRγ+ Ki67+) in organoids after 24-h drug exposure, blocking mitotic entry. In contrast, methotrexate showed the least efficacy against tumor cells. The drug responses of organoids were consistent with those of tumor cells in advanced disease. Patient-derived organoids enable the creation of a faithful model to use in examining novel therapeutics for RB.
Modulation of auditory sensory memory by chronic clinical pain and acute experimental pain: a mismatch negativity study
Authors: Fan Lu , Sun Ya-Bin , Sun Ze-Kun , Wang Ning , Luo Fei , Yu Feng , Wang Jin-Yan 
Published: October 2018

AbstractPain, especially chronic pain, can lead to cognitive deficits. Mismatch negativity (MMN) is a change-specific component of the auditory event-related brain potential (ERP) that is thought to provide a unique window into sensory memory processes. The present study was designed to determine how chronic and acute pain affects auditory sensory memory. In experiment 1, MMNs elicited by standard and deviant auditory stimuli at short and long inter-stimulus intervals (ISIs) were compared between trigeminal neuralgia (TN) patients and demographically matched healthy controls (HCs). The TN patients were found to have stronger attenuation of the MMN at longer ISIs than HCs. Correlation analysis revealed a significant positive correlation between the sensory subscale of McGill Pain Questionnaire and MMN amplitude reduction across ISI conditions. In experiment 2, MMNs recorded before, during, and after the cold pressor test were compared in healthy subjects. MMN amplitude was significantly reduced during pain exposure and recovered immediately thereafter. These results suggest that both chronic pain and acute pain can interfere with automatic change detection processes in the brain. This study provides the first evidence that chronic pain patients have a faster auditory memory trace decay than HCs.
Effects of rituximab dose on hepatitis B reactivation in patients with resolved infection undergoing immunologic incompatible kidney transplantation
Authors: Lee Juhan , Park Jun Yong , Kim Deok Gie , Lee Jee Youn , Kim Beom Seok , Kim Myoung Soo , Il Kim Soon , Kim Yu Seun , Huh Kyu Ha 
Published: October 2018

AbstractSensitized patients received desensitization therapy with rituximab for kidney transplantation. However, the impact of rituximab dose on hepatitis B virus (HBV) reactivation is unknown. Patients who underwent living donor kidney transplantation between 2008 and 2016 were grouped according to rituximab dose (control vs. standard-dose rituximab [375 mg/m2] vs. reduced-dose rituximab [200 mg/body]) for comparison of HBV reactivation. A total of 336 hepatitis B surface antigen (HBsAg)-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients underwent kidney transplantation, of whom 91 (27.1%) received rituximab for desensitization (57 standard-dose and 34 reduced-dose rituximab). During the study period, eight patients experienced HBV reactivation (three in the control group, five in the standard-dose group). In the standard-dose group, four patients experienced hepatitis flare, and one patient died due to hepatic failure. No HBV reactivation occurred in the reduced-dose group. Standard-dose rituximab significantly decreased hepatitis B surface antigen antibody titer (anti-HBs; −99.8 IU/L) at 12 months, compared with reduced-dose rituximab (−20.1 IU/L) and control (−39.1 IU/L, P = 0.017). Standard-dose rituximab (HR, 10.60; 95% CI, 2.52–44.60; P = 0.001) and anti-HBs < 100 IU/L at transplantation (HR, 9.06; 95% CI, 1.11–74.30; P = 0.04) were independent risk factors for HBV reactivation. Standard-dose rituximab significantly increased HBV reactivation risk for HBsAg-negative/anti-HBc-positive kidney transplant patients.
Microplastics increase mercury bioconcentration in gills and bioaccumulation in the liver, and cause oxidative stress and damage in Dicentrarchus labrax juveniles
Authors: Barboza Luís Gabriel Antão , Vieira Luís Russo , Branco Vasco , Carvalho Cristina , Guilhermino Lúcia 
Published: October 2018

AbstractThe presence of microplastics and several other pollutants in the marine environment is of growing concern. However, the knowledge on the toxicity of mixtures containing microplastics and other contaminants to marine species is still scarce. The main goals of this study were to investigate the oxidative stress and lipid oxidative damage potentially induced by 96 h of exposure to mercury (0.010 and 0.016 mg/L), microplastics (0.26 and 0.69 mg/L), and mixtures of the two substances (same concentrations, full factorial) in the gills and liver of D. labrax juveniles, and the possible influence of microplastics on mercury bioconcentration (gills) and bioaccumulation (liver). The results indicate that the presence of microplastics in the water increased the concentration of mercury in gills and liver of D. labrax juveniles. Microplastics and mercury, alone and in mixtures, caused oxidative stress in both organs. Based on the total induction of antioxidant enzymatic activity, the type of toxicological interaction in fish exposed to the mixture containing the lowest concentration of the two substances was addition in gills, and addition or synergism in the liver. These results stress the need to further address the role of microplastics in the bioconcentration, bioaccumulation, and toxicity of other environmental contaminants in different species.
Utilizing the Momentum in Orbital Angular Momentum: Augmented OAM induced by a $$\frac{{\boldsymbol{\pi }}}{{\bf{2}}}$$ Aperture of Three Elements
Authors: Fouda Reham M. 
Published: October 2018

AbstractThe feasibility to induce augmented dominant OAM modes by a π/2 aperture of three elements in space and weighted quasi-phase shifts is realised in this paper. It is shown through theory, numerical simulations and experimentation, that electromagnetic (EM) waves carrying non-integer OAM with dominant mode l = +1 in the microwave domain can be generated by a quarter of a full azimuthal annular aperture consisting of three elements and a weighted phase shift augmenting the expected conventional phase shift to reach Berry’s mode dominance theory of half integer l. With reference to the uncertainty principle of angular momentum and angular position, the proposed augmented OAM with weighted phase shift method seems to decrease mode uncertainties and augment mode dominance.
WISP-1 drives bone formation at the expense of fat formation in human perivascular stem cells
Authors: Meyers Carolyn A. , Xu Jiajia , Asatrian Greg , Ding Catherine , Shen Jia , Broderick Kristen , Ting Kang , Soo Chia , Peault Bruno , James Aaron W. 
Published: October 2018

AbstractThe vascular wall within adipose tissue is a source of mesenchymal progenitors, referred to as perivascular stem/stromal cells (PSC). PSC are isolated via fluorescence activated cell sorting (FACS), and defined as a bipartite population of pericytes and adventitial progenitor cells (APCs). Those factors that promote the differentiation of PSC into bone or fat cell types are not well understood. Here, we observed high expression of WISP-1 among human PSC in vivo, after purification, and upon transplantation in a bone defect. Next, modulation of WISP-1 expression was performed, using WISP-1 overexpression, WISP-1 protein, or WISP-1 siRNA. Results demonstrated that WISP-1 is expressed in the perivascular niche, and high expression is maintained after purification of PSC, and upon transplantation in a bone microenvironment. In vitro studies demonstrate that WISP-1 has pro-osteogenic/anti-adipocytic effects in human PSC, and that regulation of BMP signaling activity may underlie these effects. In summary, our results demonstrate the importance of the matricellular protein WISP-1 in regulation of the differentiation of human stem cell types within the perivascular niche. WISP-1 signaling upregulation may be of future benefit in cell therapy mediated bone tissue engineering, for the healing of bone defects or other orthopaedic applications.
Whole genome mRNA expression profiling revealed multiple deregulated pathways in stromal vascular fraction from erectile dysfunction patients
Authors: Vishnubalaji Radhakrishnan , Manikandan Muthurangan , Aldahmash Abdullah , AlJarbou Abdullah , Habous Mohamad , Alhajeri Dulaim , Almannie Raed , Alfayez Musaad , Alajez Nehad M. , Binsaleh Saleh 
Published: October 2018

Background: Stem-cell-based therapies have recently been explored in the field of erectile dysfunction (ED). However, the cellular and molecular phenotype of adipose derived stem cells (ADSCs) stromal vascular fraction (SVF) from ED patients remains largely unknown. Herein we compared the global gene expression profile in the SVF from ED patients and healthy individuals and identified altered signaling pathways between the two groups.
Methods: Samples (2–5 g) of abdominal adipose tissue from ED patients (n = 6) and healthy individual controls (n = 3) undergoing elective cosmetic liposuction were collected. Immediately after removal, SVF was separated using Collagenase type I and type IV protocol. RNA was isolated and microarray experiments were conducted using the Agilent platform. Data were normalized and pathway analyses were performed using GeneSpring software.
Results: Our data revealed multiple differentially expressed genes between the ED and control group. Hierarchical clustering based on differentially expressed mRNAs revealed clear separation of the two groups. The distribution of the top enriched pathways for the up-regulated genes indicated enrichment in inflammatory response and T-cell receptor signaling, while pathway analysis performed on the down-regulated genes revealed enrichment in mitogen-activated protein kinase, TGF-β, senescence, FAK, adipogenesis, androgen receptor, and EGF–EGFR signaling pathways in SVF from ED patient.
Conclusion: Our data revealed the existence of multiple altered signaling pathways in the SVF from ED patients, which could potentially play a role in the etiology of this disease. Therefore, therapeutic strategies targeting these pathways might provide novel therapeutic opportunity for ED patients.
MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
Authors: Zhao Xin , Yi Yaping , Meng Chao , Fang Ningyuan 
Published: October 2018

Abstract
Hypertension is a major risk factor for the development of atherosclerosis. Increased carotid intima-media thickness (CIMT) is generally considered as an early marker of atherosclerosis. Recently, circulating miRNAs have been implicated both as sensitive biomarkers and key regulators in the development of atherosclerosis. However, the biological functions and molecular regulatory mechanisms for miR-575 on angiogenesis remain unknown. In our study, we first identified up-regulation of circulating miR-575 in plasma of essential hypertensive patients with increased CIMT (iCIMT) compared with those patients with normal CIMT (nCIMT). Furthermore, the overexpression of miR-575 in human umbilical vein endothelial cells (HUVECs) by its mimics significantly inhibited migration and proliferation as well as induction of apoptosis of HUVECs. Inhibition of miR-575 performed the reverse effects of HUVECs. We further suggested Rab5B was the downstream target of miR-575 and knockdown of Rab5B significantly inhibited migration and proliferation of HUVECs. Overexpression of Rab5B largely rescued the miR-575-mediated impairment of angiogenesis processes including: cell proliferation, migration, and apoptosis as well as activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK) signaling. Therefore, our results uncover a novel role of miR-575 in endothelial cells, implying a potential biomarker and clinical target for atherosclerosis in hypertensive patients.
Weight optimisation of coreless axial‐flux permanent magnet machines
Authors: Subotic Ivan , Gammeter Christoph , Tüysüz Arda , Kolar Johann W. 
Published: October 2018

This study explores the upper limits in power‐to‐weight and torque‐to‐weight ratios of coreless axial‐flux machines with permanent magnets. Moreover, it provides a comprehensive multifunctional optimisation procedure that is utilised for obtaining these limits. The procedure encompasses analytical analysis of electro‐magnetic, thermal and structural (mechanical) aspects of axial‐flux machines. Obtaining global minima is ensured by considering the whole machine design space, and mapping it into the performance space, where a Pareto front can be easily identified. From it, an optimal motor/generator for airborne wind turbines is identified. The design has a power‐to‐weight ratio of 6.4 kW/kg (19 Nm/kg at 3200 rpm) including structural (purely mechanical) parts, at an efficiency of 95%. This is a significantly higher ratio than the one in modern commercial machines or designs reported in the literature. Therefore, the resulting machine is manufactured and experimentally tested in order to verify the claimed limits and the optimisation methodology.
Macht Zucker glücklich? Macht Zucker süchtig?
Authors: Albayrak Özgur 
Published: October 2018

ZusammenfassungZucker ist ein essenzieller Energielieferant für den menschlichen Körper. Es wirkt im Gehirn auf neuroanatomische Strukturen, die für den Energiehaushalt als auch für das Belohnungssystem und für die Emotionsregulation verantwortlich sind. Der Überkonsum von Zucker ist schädlich für den Körper und trägt zur Ausbildung von metabolischen Krankheiten wie Adipositas und Diabetes mellitus bei. Erst in jüngster Zeit widmen sich Wissenschaftler der Frage, ob die Wirkung von Zucker auf das menschliche Belohnungssystem im Gehirn zu einer Abhängigkeit führen kann – ähnlich wie es bei suchterzeugenden Substanzen wie Alkohol oder Heroin der Fall ist. Dieser Beitrag widmet sich dieser Fragestellung und gibt einen kritischen und aktuellen Überblick.
Zucker: Kulturgeschichte und Konsumstruktur eines umstrittenen Lebensmittels
Authors: Hirschfelder Gunther 
Published: October 2018

ZusammenfassungZucker steht derzeit unter Generalverdacht: Ernährungsaufklärung fokussiert auf Süßigkeiten, Softdrinks und versteckten Zucker in „Convenience-Produkten“. Die Medien haben ihn zu ihrem Lieblingsfeind erkoren. Gleichwohl essen die Deutschen so viel Zucker wie nie: 32 kg pro Jahr – das entspricht 22 Teelöffel pro Tag und damit mehr als doppelt so viel wie die WHO derzeit empfiehlt.Dass Ernährungsbildung dabei allenfalls bedingt funktioniert ist das Eine. Das Andere: Zucker ist mehr als Industrieprodukt, Füllstoff, Dickmacher oder schneller Energielieferant: Zucker ist auch ein Kulturgut. In der Entwicklungsgeschichte der Menschheit steht er für gesuchten und guten Geschmack wie auch für Energie, somit für Leben beziehungsweise Überleben. Spätestens seit den frühen Hochkulturen und verstärkt in der Antike ist eine besondere Wertschätzung von süßen Früchten und Honig erkennbar, die in medizinischer Verwendung Niederschlag fand.Die Entdeckung des aus dem pazifischen Raum stammenden Zuckerrohrs und der plantagenmäßige Anbau an der europäischen Peripherie brachten das Abendland dann seit dem Mittelalter in engeren Kontakt mit dem Luxusgut Zucker. Fundamentaler Wandel erfolgte durch den Columbian Exchange: Seitdem afrikanische Sklaven gezwungen wurden, den amerikanischen Kolonien Zucker für den europäischen Markt anzubauen, stieg der Konsum sprunghaft an und demokratisierte sich seit dem 19. Jahrhundert. Kritik am Zucker wurde zunächst nicht laut, auch nicht in der Epoche des Massenkonsums der Nachkriegszeit.Erst als der Verbrauch weiter stieg und die Gesellschaft am Ende des 20. Jahrhunderts zunehmend gesundheitsbewusst wurde – und als die Frage nach der vermeintlich richtigen Ernährung zur ideologischen Leitperspektive avanciert war, geriet Zucker massiv in die Kritik. Wer die heutige Rolle des Zuckers verstehen will, sollte die historischen Hintergründe und die kulturellen Determinanten berücksichtigen.
Contrast-Enhanced Ultrasound of Benign Focal Liver Lesions
Authors: Dietrich Christoph 
Published: October 2018

AbstractThe diagnostic handling of benign focal liver lesions (FLLs) is a challenge and it is difficult to avoid over- and underdiagnosis. Conventional B-mode ultrasound and contrast-enhanced ultrasound (CEUS) are the first-line imaging methods to detect and characterize FLLs. This CME article discusses the diagnostic workup of benign liver tumors.
Vascularization of Primary, Peripheral Lung Carcinoma in CEUS – A Retrospective Study (n = 89 Patients)
Authors: Findeisen Hajo , Trenker Corinna , Figiel Jens , Greene Brandon H. , Görg Konrad , Görg Christian 
Published: October 2018

Abstract
Purpose To describe the vascularization of peripheral lung carcinoma in CEUS and to compare with B-mode ultrasound (US) and clinical data.
Materials and Methods From April 2004 until September 2015, n = 89 patients with peripheral lung carcinoma were investigated by B-mode US and CEUS. The extent (EE: hypoechoic, hyperechoic), homogeneity (HE: homogeneous, inhomogeneous) and time of enhancement (TE) have been defined. Early pulmonary-arterial enhancement (PA) before contrast floating to the thoracic wall was differentiated from simultaneous or delayed bronchial-arterial enhancement (BA). CEUS parameters were compared by B-mode US and histology.
Results n = 25 patients had early PA enhancement (TE: 8 ± 3.7 s), and n = 64 (72 %) had simultaneous/delayed BA enhancement (TE: 17.6 ± 6.2 s) (p < 0.001). PA enhancement (EE/HE) was hyperechoic (n = 11/25), homogeneous (n = 11/25) and showed an air bronchogram more often (n = 11/17, p < 0.001). BA enhancement (EE/HE) was frequently hypoechoic (n = 34/64) and inhomogeneous (n = 54/64). BA enhancement was associated with necrosis (n = 36/42, p = 0.009). PA and BA enhancement distributed to different histologies: n = 42 adenocarcinomas (18 PA, 24 BA), n = 30 squamous cell carcinomas (4 PA, 26 BA), n = 13 other types of NSCLC (3 PA, 10 BA), and n = 4 SCLC (0 PA, 4 BA) (p = 0.016).
Conclusion The vascularization of peripheral lung carcinomas is heterogeneous and is influenced by histology. In this study, lung carcinomas are predominantly supplied by bronchial arteries, whereas a part of adenocarcinomas and non-adenocarcinomas show PA enhancement.
In Vitro Reversal of the Anti-Aggregant Effect of Ticagrelor Using Untreated Platelets
Authors: Kruger Paul , Hirsh Jack , Bhagirath Vinai , Xu Ke , Dale Brian , de Vries Tim , Ginsberg Jeffrey , Eikelboom John , Chan Noel 
Published: October 2018

Background Ticagrelor is an anti-platelet agent that is indicated for prevention of thrombosis after acute coronary syndrome or intra-coronary artery stent implantation, but it increases the risk of bleeding. Platelet transfusion has the potential to treat or prevent bleeding in patients taking ticagrelor, but the optimal quantity of platelets and timing of administration have not been fully defined.
Methods and Results Ten healthy subjects took ticagrelor in combination with acetylsalicylic acid for 5 days, and had blood collected prior to treatment and at 2, 10, 24, 48, 72 and 96 hours after the last doses. The potential of platelet transfusion to prevent or reverse bleeding was evaluated by mixing subject and donor platelet-rich plasma in vitro in nine different proportions, and measuring adenosine diphosphate-mediated aggregation by light transmission aggregometry. Spontaneous offset of the anti-aggregant effect of ticagrelor occurred gradually and was complete at 72 hours after the last dose. The addition of donor platelets enhanced the recovery. The addition of the equivalent of six apheresis platelet units produced a 50% relative reversal at 10 hours, and > 90% reversal at 24 hours.
Conclusion Donor platelets enhance reversal of the anti-aggregant effect of ticagrelor in vitro. Donor platelets given in clinically relevant amounts partially reversed ticagrelor at 10 hours after the last dose, and almost fully reversed ticagrelor at 24 hours. The results inform on the potential to reverse ticagrelor in patients who develop bleeding or require emergency surgery.
Transcription initiation defines kinetoplast RNA boundaries
Authors: Sement François M. , Suematsu Takuma , Zhang Liye , Yu Tian , Huang Lan , Aphasizheva Inna , Aphasizhev Ruslan 
Published: October 2018

Significance
It is held that in trypanosomes both mitochondrial DNA strands are transcribed into polycistronic precursors. An unknown endonuclease presumably cleaves primary transcripts to liberate monocistronic mRNAs. However, this model is incongruent with an established event of mRNA processing by 3′–5′ exonucleolytic degradation. Our work suggests that each gene is transcribed individually and the pre-mRNA undergoes 5′-end modification and controlled 3′-end trimming. We identified the pyrophosphohydrolase protein complex as responsible for pyrophosphate removal from the 5′ nucleoside and mRNA stabilization. We characterized antisense noncoding RNAs originating near mRNA 3′ termini and investigated their potential role in 3′-end demarcation. It is conceivable that transcription, in addition to mRNA editing and decay, plays a significant role in regulation of mitochondrial gene expression.
Nitrogen regulation by natural systems in “unnatural” landscapes: denitrification in ultra-urban coastal ecosystems
Authors: Rosenzweig Bernice R. , Groffman Peter M. , Zarnoch Chester B. , Branco Brett F. , Hartig Ellen K. , Fitzpatrick James , Forgione Helen M. , Parris Adam 
Published: October 2018

ABSTRACT
Dense cities represent biogeochemical hot spots along the shoreline, concentrating fixed nitrogen that is subsequently discharged into adjacent coastal receiving waters. Thus, the ecosystem services provided by natural systems in highly urban environments can play a particularly important role in the global nitrogen cycle. In this paper, we review the recent literature on nitrogen regulation by temperate coastal ecosystems, with a focus on how the distinct physical and biogeochemical features of the urban landscape can affect the provision of this ecosystem service. We use Jamaica Bay, an ultra-urbanized coastal lagoon in the United States of America, as a demonstrative case study. Based on simple areal and tidal-based calculations, the natural systems of Jamaica Bay remove ~ 24% of the reactive nitrogen discharged by wastewater treatment plants. However, this estimate does not represent the dynamic nature of urban nitrogen cycling represented in the recent literature and highlights key research needs and opportunities. Our review reveals that ecosystem-facilitated denitrification may be significant in even the most densely urbanized coastal landscapes, but critical uncertainties currently limit incorporation of this ecosystem service in environmental management.