bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro
Authors: Dituri Francesco , Scialpi Rosanna , Schmidt Tannin A. , Frusciante Martina , Mancarella Serena , Lupo Luigi Giovanni , Villa Erica , Giannelli Gianluigi 
Published: November 2020

AbstractSorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
Deep learning-enabled breast cancer hormonal receptor status determination from base-level H&E stains
Authors: Naik Nikhil , Madani Ali , Esteva Andre , Keskar Nitish Shirish , Press Michael F. , Ruderman Daniel , Agus David B. , Socher Richard 
Published: November 2020

AbstractFor newly diagnosed breast cancer, estrogen receptor status (ERS) is a key molecular marker used for prognosis and treatment decisions. During clinical management, ERS is determined by pathologists from immunohistochemistry (IHC) staining of biopsied tissue for the targeted receptor, which highlights the presence of cellular surface antigens. This is an expensive, time-consuming process which introduces discordance in results due to variability in IHC preparation and pathologist subjectivity. In contrast, hematoxylin and eosin (H&E) staining—which highlights cellular morphology—is quick, less expensive, and less variable in preparation. Here we show that machine learning can determine molecular marker status, as assessed by hormone receptors, directly from cellular morphology. We develop a multiple instance learning-based deep neural network that determines ERS from H&E-stained whole slide images (WSI). Our algorithm—trained strictly with WSI-level annotations—is accurate on a varied, multi-country dataset of 3,474 patients, achieving an area under the curve (AUC) of 0.92 for sensitivity and specificity. Our approach has the potential to augment clinicians’ capabilities in cancer prognosis and theragnosis by harnessing biological signals imperceptible to the human eye.
Discontinuous transition to loop formation in optimal supply networks
Authors: Kaiser Franz , Ronellenfitsch Henrik , Witthaut Dirk 
Published: November 2020

AbstractThe structure and design of optimal supply networks is an important topic in complex networks research. A fundamental trait of natural and man-made networks is the emergence of loops and the trade-off governing their formation: adding redundant edges to supply networks is costly, yet beneficial for resilience. Loops typically form when costs for new edges are small or inputs uncertain. Here, we shed further light on the transition to loop formation. We demonstrate that loops emerge discontinuously when decreasing the costs for new edges for both an edge-damage model and a fluctuating sink model. Mathematically, new loops are shown to form through a saddle-node bifurcation. Our analysis allows to heuristically predict the location and cost where the first loop emerges. Finally, we unveil an intimate relationship among betweenness measures and optimal tree networks. Our results can be used to understand the evolution of loop formation in real-world biological networks.
Transient commensal clonal interactions can drive tumor metastasis
Authors: Naffar-Abu Amara Suha , Kuiken Hendrik J. , Selfors Laura M. , Butler Timothy , Leung Marco L. , Leung Cheuk T. , Kuhn Elaine P. , Kolarova Teodora , Hage Carina , Ganesh Kripa , Panayiotou Richard , Foster Rosemary , Rueda Bo R. , Aktipis Athena , Spellman Paul , Ince Tan A. , Xiu Joanne , Oberley Matthew , Gatalica Zoran , Navin Nicholas , Mills Gordon B. , Bronson Rodrick T. , Brugge Joan S. 
Published: November 2020

AbstractThe extent and importance of functional heterogeneity and crosstalk between tumor cells is poorly understood. Here, we describe the generation of clonal populations from a patient-derived ovarian clear cell carcinoma model which forms malignant ascites and solid peritoneal tumors upon intraperitoneal transplantation in mice. The clonal populations are engineered with secreted Gaussia luciferase to monitor tumor growth dynamics and tagged with a unique DNA barcode to track their fate in multiclonal mixtures during tumor progression. Only one clone, CL31, grows robustly, generating exclusively malignant ascites. However, multiclonal mixtures form large solid peritoneal metastases, populated almost entirely by CL31, suggesting that transient cooperative interclonal interactions are sufficient to promote metastasis of CL31. CL31 uniquely harbors ERBB2 amplification, and its acquired metastatic activity in clonal mixtures is dependent on transient exposure to amphiregulin, which is exclusively secreted by non-tumorigenic clones. Amphiregulin enhances CL31 mesothelial clearance, a prerequisite for metastasis. These findings demonstrate that transient, ostensibly innocuous tumor subpopulations can promote metastases via “hit-and-run” commensal interactions.
Risk of yellow fever virus transmission in the Asia-Pacific region
Authors: Lataillade Lucy de Guilhem de , Vazeille Marie , Obadia Thomas , Madec Yoann , Mousson Laurence , Kamgang Basile , Chen Chun-Hong , Failloux Anna-Bella , Yen Pei-Shi 
Published: November 2020

AbstractHistorically endemic to Sub-Saharan Africa and South America, yellow fever is absent from the Asia-Pacific region. Yellow fever virus (YFV) is mainly transmitted by the anthropophilic Aedes mosquitoes whose distribution encompasses a large belt of tropical and sub tropical regions. Increasing exchanges between Africa and Asia have caused imported YFV incidents in non-endemic areas, which are threatening Asia with a new viral emergence. Here, using experimental infections of field-collected mosquitoes, we show that Asian-Pacific Aedes mosquitoes are competent vectors for YFV. We observe that Aedes aegypti populations from Singapore, Taiwan, Thailand, and New Caledonia are capable of transmitting YFV 14 days after oral infections, with a number of viral particles excreted from saliva reaching up to 23,000 viral particles. These findings represent the most comprehensive assessment of vector competence and show that Ae. aegypti mosquitoes from the Asia-Pacific region are highly competent to YFV, corroborating that vector populations are seemingly not a brake to the emergence of yellow fever in the region.
In-situ monitoring of interface proximity effects in ultrathin ferroelectrics
Authors: Strkalj Nives , Gattinoni Chiara , Vogel Alexander , Campanini Marco , Haerdi Rea , Rossi Antonella , Rossell Marta D. , Spaldin Nicola A. , Fiebig Manfred , Trassin Morgan 
Published: November 2020

AbstractThe development of energy-efficient nanoelectronics based on ferroelectrics is hampered by a notorious polarization loss in the ultrathin regime caused by the unscreened polar discontinuity at the interfaces. So far, engineering charge screening at either the bottom or the top interface has been used to optimize the polarization state. Yet, it is expected that the combined effect of both interfaces determines the final polarization state; in fact the more so the thinner a film is. The competition and cooperation between interfaces have, however, remained unexplored so far. Taking PbTiO3 as a model system, we observe drastic differences between the influence of a single interface and the competition and cooperation of two interfaces. We investigate the impact of these configurations on the PbTiO3 polarization when the interfaces are in close proximity, during thin-film synthesis in the ultrathin limit. By tailoring the interface chemistry towards a cooperative configuration, we stabilize a robust polarization state with giant polarization enhancement. Interface cooperation hence constitutes a powerful route for engineering the polarization in thin-film ferroelectrics towards improved integrability for oxide electronics in reduced dimension.
RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis
Authors: Farooq Muhammad , Lindbæk Louise , Krogh Nicolai , Doganli Canan , Keller Cecilie , Mönnich Maren , Gonçalves André Brás , Sakthivel Srinivasan , Mang Yuan , Fatima Ambrin , Andersen Vivi Søgaard , Hussain Muhammad S. , Eiberg Hans , Hansen Lars , Kjaer Klaus Wilbrandt , Gopalakrishnan Jay , Pedersen Lotte Bang , Møllgård Kjeld , Nielsen Henrik , Baig Shahid. M. , Tommerup Niels , Christensen Søren Tvorup , Larsen Lars Allan 
Published: November 2020

AbstractPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.
High-density surface electromyography signals during isometric contractions of elbow muscles of healthy humans
Authors: Rojas-Martínez Mónica , Serna Leidy Yanet , Jordanic Mislav , Marateb Hamid Reza , Merletti Roberto , Mañanas Miguel Ángel 
Published: November 2020

AbstractThis paper presents a dataset of high-density surface EMG signals (HD-sEMG) designed to study patterns of sEMG spatial distribution over upper limb muscles during voluntary isometric contractions. Twelve healthy subjects performed four different isometric tasks at different effort levels associated with movements of the forearm. Three 2-D electrode arrays were used for recording the myoelectric activity from five upper limb muscles: biceps brachii, triceps brachii, anconeus, brachioradialis, and pronator teres. Technical validation comprised a signals quality assessment from outlier detection algorithms based on supervised and non-supervised classification methods. About 6% of the total number of signals were identified as “bad” channels demonstrating the high quality of the recordings. In addition, spatial and intensity features of HD-sEMG maps for identification of effort type and level, have been formulated in the framework of this database, demonstrating better performance than the traditional time-domain features. The presented database can be used for pattern recognition and MUAP identification among other uses.
Indoor spectroradiometric characterization of plastic litters commonly polluting the Mediterranean Sea: toward the application of multispectral imagery
Authors: Corbari L. , Maltese A. , Capodici F. , Mangano M. C. , Sarà G. , Ciraolo G. 
Published: November 2020

AbstractAround 350 million tonnes of plastics are annually produced worldwide. A remarkable percentage of these products is dispersed in the environment, finally reaching and dispersed in the marine environment. Recent field surveys detected microplastics’ concentrations in the Mediterranean Sea. The most commonly polymers found were polyethylene, polypropylene and viscose, ethylene vinyl acetate and polystyrene. In general, the in-situ monitoring of microplastic pollution is difficult and time consuming. The main goals of this work were to spectrally characterize the most commonly polymers and to quantify their spectral separability that may allow to determine optimal band combinations for imaging techniques monitoring. The spectral signatures of microplastics have been analysed in laboratory, both in dry condition and on water surface, using a full spectrum spectroradiometer. The theoretical use of operational satellite images for remote sensing monitoring was investigated by quantifying the spectral separability achievable by their sensors. The WorldView-3 sensor appears the most suitable for the monitoring but better average spectral separability are expected using the recently released PRISMA images. This research was preparatory to further outdoor experiments needed to better simulate the real acquisition condition.
Oncologic and obstetric outcomes after conization for adenocarcinoma in situ or stage IA1 cervical cancer
Authors: Wang Xiaoyu , Bi Yalan , Wu Huanwen , Wu Ming , Li Lei 
Published: November 2020

AbstractThis study aims to reveal the risk factors associated with recurrence or new-onset high-grade squamous intraepithelial lesions (HSILs) or more severe lesions (HSILs +) and analyze obstetrical outcomes in patients with adenocarcinoma in situ (AIS) or stage IA1 cervical cancer patients after conization. A retrospective cohort study was developed from January 1, 2002, and July 1, 2018, in a single center, where all patients with AIS or stage IA1 cervical cancer who accepted conization for primary surgery were reviewed and followed up until July 1, 2019, for the pathological findings of HSILs + and obstetric outcomes. Two hundred and seventeen patients were identified, including 114 cases of AIS, 76 cases of stage IA1 squamous cell carcinoma (SCC) and 27 cases of stage IA1 adenocarcinoma (ADC). A total of 88 (40.6%) patients had an intact uterus without radiotherapy. Five patients experienced HSIL+ recurrence. The cumulative 3-, 5- and 10-year incidence rates of HSILs + were 1.0%, 1.5% and 2.0%, respectively. No significant risk factors, including primary disease, margin status and hysterectomy, were associated with recurrence. Twenty (66.7%) of 30 patients who attempted pregnancy had 23 successful pregnancies, which result in 7 miscarriages, 16 live births and 5 preterm births. Age at conization was the only independent risk factor associated with pregnancy, live births and preterm births. In conclusion, conization is safe for young women with AIS, stage IA1 SCC and ADC who desire future fertility, and the associated HSIL recurrence rate is low. Increased age significantly lowered the conception or live birth rate.
Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo
Authors: Motta Sarah E. , Fioretta Emanuela S. , Lintas Valentina , Dijkman Petra E. , Hilbe Monika , Frese Laura , Cesarovic Nikola , Loerakker Sandra , Baaijens Frank P. T. , Falk Volkmar , Hoerstrup Simon P. , Emmert Maximilian Y. 
Published: November 2020

AbstractRegenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. However, a thorough understanding on how TEHV-geometry impacts the underlying host cell response, which in return determines tissue remodeling, is not yet fully understood. To assess that, we here present a comparative samples evaluation derived from our first- and second-generation TEHVs. We performed an in-depth qualitative and quantitative (immuno-)histological analysis focusing on key-players of the inflammatory and remodeling cascades (M1/M2 macrophages, α-SMA+- and endothelial cells). First-generation TEHVs were prone to chronic inflammation, showing a high presence of macrophages and α-SMA+-cells, hinge-area thickening, and delayed endothelialization. Second-generation TEHVs presented with negligible amounts of macrophages and α-SMA+-cells, absence of hinge-area thickening, and early endothelialization. Our results suggest that TEHV-geometry can significantly influence the host cell response by determining the infiltration and presence of macrophages and α-SMA+-cells, which play a crucial role in orchestrating TEHV remodeling.
Intact in vivo visualization of telencephalic microvasculature in medaka using optical coherence tomography
Authors: Suzuki Takashi , Ueno Tomohiro , Oishi Naoya , Fukuyama Hidenao 
Published: November 2020

AbstractTo date, various human disease models in small fish—such as medaka (Oryzias lapties)—have been developed for medical and pharmacological studies. Although genetic and environmental homogeneities exist, disease progressions can show large individual differences in animal models. In this study, we established an intact in vivo angiographic approach and explored vascular networks in the telencephalon of wild-type adult medaka using the spectral-domain optical coherence tomography. Our approach, which required neither surgical operations nor labeling agents, allowed to visualize blood vessels in medaka telencephala as small as about 8 µm, that is, almost the size of the blood cells of medaka. Besides, we could show the three-dimensional microvascular distribution in the medaka telencephalon. Therefore, the intact in vivo imaging via optical coherence tomography can be used to perform follow-up studies on cerebrovascular alterations in metabolic syndrome and their associations with neurodegenerative disease models in medaka.
Fungus-originated genes in the genomes of cereal and pasture grasses acquired through ancient lateral transfer
Authors: Shinozuka Hiroshi , Shinozuka Maiko , de Vries Ellen M. , Sawbridge Timothy I. , Spangenberg German C. , Cocks Benjamin G. 
Published: November 2020

AbstractEvidence for ancestral gene transfer between Epichloë fungal endophyte ancestors and their host grass species is described. From genomes of cool-season grasses (the Poeae tribe), two Epichloë-originated genes were identified through DNA sequence similarity analysis. The two genes showed 96% and 85% DNA sequence identities between the corresponding Epichloë genes. One of the genes was specific to the Loliinae sub-tribe. The other gene was more widely conserved in the Poeae and Triticeae tribes, including wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.). The genes were independently transferred during the last 39 million years. The transferred genes were expressed in plant tissues, presumably retaining molecular functions. Multiple gene transfer events between the specific plant and fungal lineages are unique. A range of cereal crops is included in the Poeae and Triticeae tribes, and the Loliinae sub-tribe is consisted of economically important pasture and forage crops. Identification and characterisation of the 'natural' adaptation transgenes in the genomes of cereals, and pasture and forage grasses, that worldwide underpin the production of major foods, such as bread, meat, and milk, may change the ‘unnatural’ perception status of transgenic and gene-edited plants.
Towards image-based cancer cell lines authentication using deep neural networks
Authors: Mzurikwao Deogratias , Khan Muhammad Usman , Samuel Oluwarotimi Williams , Cinatl Jindrich , Wass Mark , Michaelis Martin , Marcelli Gianluca , Ang Chee Siang 
Published: November 2020

AbstractAlthough short tandem repeat (STR) analysis is available as a reliable method for the determination of the genetic origin of cell lines, the occurrence of misauthenticated cell lines remains an important issue. Reasons include the cost, effort and time associated with STR analysis. Moreover, there are currently no methods for the discrimination between isogenic cell lines (cell lines of the same genetic origin, e.g. different cell lines derived from the same organism, clonal sublines, sublines adapted to grow under certain conditions). Hence, additional complementary, ideally low-cost and low-effort methods are required that enable (1) the monitoring of cell line identity as part of the daily laboratory routine and 2) the authentication of isogenic cell lines. In this research, we automate the process of cell line identification by image-based analysis using deep convolutional neural networks. Two different convolutional neural networks models (MobileNet and InceptionResNet V2) were trained to automatically identify four parental cancer cell line (COLO 704, EFO-21, EFO-27 and UKF-NB-3) and their sublines adapted to the anti-cancer drugs cisplatin (COLO-704rCDDP1000, EFO-21rCDDP2000, EFO-27rCDDP2000) or oxaliplatin (UKF-NB-3rOXALI2000), hence resulting in an eight-class problem. Our best performing model, InceptionResNet V2, achieved an average of 0.91 F1-score on tenfold cross validation with an average area under the curve (AUC) of 0.95, for the 8-class problem. Our best model also achieved an average F1-score of 0.94 and 0.96 on the authentication through a classification process of the four parental cell lines and the respective drug-adapted cells, respectively, on a four-class problem separately. These findings provide the basis for further development of the application of deep learning for the automation of cell line authentication into a readily available easy-to-use methodology that enables routine monitoring of the identity of cell lines including isogenic cell lines. It should be noted that, this is just a proof of principal that, images can also be used as a method for authentication of cancer cell lines and not a replacement for the STR method.