bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success
Authors: Na Young-Soon , Ryu Min-Hee , Park Young Soo , Lee Chae-Won , Lee Ju-Kyung , Park Yangsoon , Park Jung Min , Ma Jungeun , Kang Yoon-Koo 
Published: May 2020

AbstractPatient-derived xenografts (PDXs) can represent the heterogeneity and histological characteristics of tumors and are thus useful for testing the efficacy of anti-cancer drugs; however, PDXs are difficult to generate, especially for gastrointestinal stromal tumor (GIST). We analyzed the clinicopathologic factors associated with the successful establishment of GIST PDX in NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ mice. We used 185 GIST tumor fragments from patients who underwent surgical resection prior to (n = 66; 35.7%) and after treatment (n = 119; 64.3%) with tyrosine kinase inhibitors. The overall success rate of PDX establishment was 17%; in univariate analysis, engraftment success was associated with after TKI treatment, larger tumor size, higher mitotic count, higher Ki-67 index, higher cellularity, presence of tumor necrosis, primary mutations in KIT exon 11, and originating from metastatic lesions. In multivariate analysis, higher Ki-67 index, after TKI treatment, and larger tumor size were independent factors for engraftment success. Immunohistochemistry in representative samples further corroborated the above results. These results will be useful in the establishment of PDX models from GISTs.
Niche shifts and environmental non-equilibrium undermine the usefulness of ecological niche models for invasion risk assessments
Authors: Pili Arman N. , Tingley Reid , Sy Emerson Y. , Diesmos Mae Lowe L. , Diesmos Arvin C. 
Published: May 2020

AbstractNiche shifts and environmental non-equilibrium in invading alien species undermine niche-based predictions of alien species’ potential distributions and, consequently, their usefulness for invasion risk assessments. Here, we compared the realized climatic niches of four alien amphibian species (Hylarana erythraea, Rhinella marina, Hoplobatrachus rugulosus, andKaloula pulchra) in their native and Philippine-invaded ranges to investigate niche changes that have unfolded during their invasion and, with this, assessed the extent of niche conservatism and environmental equilibrium. We investigated how niche changes affected reciprocal transferability of ecological niche models (ENMs) calibrated using data from the species’ native and Philippine-invaded ranges, and both ranges combined. We found varying levels of niche change across the species’ realized climatic niches in the Philippines: climatic niche shift forH. rugulosus; niche conservatism forR. marinaandK. pulchra; environmental non-equilibrium in the Philippine-invaded range for all species; and environmental non-equilibrium in the native range or adaptive changes post-introduction for all species exceptH. erythraea. Niche changes undermined the reciprocal transferability of ENMs calibrated using native and Philippine-invaded range data. Our paper highlights the difficulty of predicting potential distributions given niche shifts and environmental non-equilibrium; we suggest calibrating ENMs with data from species’ combined native and invaded ranges, and to regularly reassess niche changes and recalibrate ENMs as species’ invasions progress.
Mesoscale computational protocols for the design of highly cooperative bivalent macromolecules
Authors: Saurabh Suman , Piazza Francesco 
Published: May 2020

AbstractThe last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while it is widely accepted that large-scale flexibility (10–100 nm) and free/constrained dynamics (100 ns -μs) control the activity of such novel molecules, computational strategies at the mesoscale still lag behind experiments in optimizing the design of crucial features, such as the binding cooperativity (a.k.a. avidity). In this study, we introduced different coarse-grained models of a polymer-linked, two-nanobody composite molecule, with the aim of laying down the physical bases of a thorough computational drug design protocol at the mesoscale. We show that the calculation of suitable potentials of mean force allows one to apprehend the nature, range and strength of the thermodynamic forces that govern the motion of free and wall-tethered molecules. Furthermore, we develop a simple computational strategy to quantify the encounter/dissociation dynamics between the free end of a wall-tethered molecule and the surface, at the roots of binding cooperativity. This procedure allows one to pinpoint the role of internal flexibility and weak non-specific interactions on the kinetic constants of the nanobody-wall encounter and dissociation. Finally, we quantify the role and weight of rare events, which are expected to play a major role in real-life situations, such as in the immune synapse, where the binding kinetics is likely dominated by fluctuations.
Identifying trade-offs between biodiversity conservation and ecosystem services delivery for land-use decisions
Authors: Fastré Constance , Possingham Hugh P. , Strubbe Diederik , Matthysen Erik 
Published: May 2020

AbstractSustainable land-use management must account for the potential trade-offs between biodiversity conservation, productive land uses and ecosystem services. In this study, we used Marxan with Zones to generate land use plans that optimize conservation, farming and forestry land uses to reach biodiversity targets while minimizing the opportunity cost for local communities in an inhabited but data-poor National Park in the Andes of Bolivia. Based on six alternative land-use plans, we identified the synergies and trade-offs between the biodiversity benefits achieved in the different plans and the delivery of four locally important water-related ecosystem services modeled with the web-based tool AguAAndes. Although we find synergies between the conservation of high altitudePolylepiswoodlands and their associated avifauna and three of the ecosystem services investigated, soil erosion levels were actually higher in scenarios with higher achieved biodiversity benefits. Our study shows how systematic conservation planning and ecosystem service delivery modelling can be used to solve land-use conflicts and identify trade-offs between biodiversity conservation and ecosystem services in a data-poor tropical area.
Prostaglandin F2α agonist-induced suppression of 3T3-L1 cell adipogenesis affects spatial formation of extra-cellular matrix
Authors: Ida Yosuke , Hikage Fumihito , Itoh Kaku , Ida Haruka , Ohguro Hiroshi 
Published: May 2020

AbstractTo establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed. Upon adipogenesis of the 3T3-L1 organoid, the effects of either Bimatoprost acid (BIM-A), or PGF2α were examined. During the adipogenesis, organoid size, lipid staining by BODIPY and expression of the extracellular matrix (ECM) by immunocytochemistry and/or quantitative PCR were employed. The size of the organoid increased remarkably during the adipogenesis, while such increases were significantly inhibited by the presence of PGF2α or BIM-A. BODIPY positive lipid-laden cells significantly increased during the adipogenesis, while in contrast they were greatly suppressed by the presence of PGF2α. Characteristic and spatial changes in ECM expressions observed upon adipogenesis were greatly modified by the presence of PGs. Our present study using a 3D tissue culture may be a suitable strategy toward understanding disease etiology of DUES.
Identification of circular RNAs in porcine sperm and evaluation of their relation to sperm motility
Authors: Gòdia Marta , Castelló Anna , Rocco Martina , Cabrera Betlem , Rodríguez-Gil Joan Enric , Balasch Sam , Lewis Craig , Sánchez Armand , Clop Alex 
Published: May 2020

AbstractCircular RNAs (circRNAs) are emerging as a novel class of noncoding RNAs which potential role as gene regulators is quickly gaining interest. circRNAs have been studied in different tissues and cell types across several animal species. However, a thorough characterization of the circRNAome in ejaculated sperm remains unexplored. In this study, we profiled the sperm circRNA catalogue using 40 porcine ejaculates. A complex population of 1,598 circRNAs was shared in at least 30 of the 40 samples. Generally speaking, the predicted circRNAs presented low abundances and were tissue-specific. Around 80% of the circRNAs identified in the boar sperm were reported as novel. Results from abundance correlation between circRNAs and miRNAs together with the prediction of microRNA (miRNA) target sites in circRNAs suggested that circRNAs may act as miRNA sponges. Moreover, we found significant correlations between the abundance of 148 exonic circRNAs and sperm motility parameters. Two of these correlations, involving ssc_circ_1458 and ssc_circ_1321, were confirmed by RT-qPCR using 36 additional samples with extreme and opposite sperm motility values. Our study provides a thorough characterization of circRNAs in sperm and suggests that circRNAs hold potential as noninvasive biomarkers for sperm quality and male fertility.
Finite deformation elastography of articular cartilage and biomaterials based on imaging and topology optimization
Authors: Cai Luyao , Nauman Eric A. , Pedersen Claus B. W. , Neu Corey P. 
Published: May 2020

AbstractTissues and engineered biomaterials exhibit exquisite local variation in stiffness that defines their function. Conventional elastography quantifies stiffness in soft (e.g. brain, liver) tissue, but robust quantification in stiff (e.g. musculoskeletal) tissues is challenging due to dissipation of high frequency shear waves. We describe new development of finite deformation elastography that utilizes magnetic resonance imaging of low frequency, physiological-level (large magnitude) displacements, coupled to an iterative topology optimization routine to investigate stiffness heterogeneity, including spatial gradients and inclusions. We reconstruct 2D and 3D stiffness distributions in bilayer agarose hydrogels and silicon materials that exhibit heterogeneous displacement/strain responses. We map stiffness in porcine and sheep articular cartilage deep within the bony articular joint space in situ for the first time. Elevated cartilage stiffness localized to the superficial zone is further related to collagen fiber compaction and loss of water content during cyclic loading, as assessed by independent T2 measurements. We additionally describe technical challenges needed to achieve in vivo elastography measurements. Our results introduce new functional imaging biomarkers, which can be assessed nondestructively, with clinical potential to diagnose and track progression of disease in early stages, including osteoarthritis or tissue degeneration.
Clinical utility and cost-effectiveness of bacterial 16S rRNA and targeted PCR based diagnostic testing in a UK microbiology laboratory network
Authors: Aggarwal Dinesh , Kanitkar Tanmay , Narouz Michael , Azadian Berge S. , Moore Luke S. P. , Mughal Nabeela 
Published: May 2020

Abstract16S ribosomal-ribonucleic acid polymerase chain reaction (PCR) and targeted PCR aid microbiological diagnosis in culture-negative clinical samples. Despite routine clinical use, there remains a paucity of data on their effectiveness across a variety of clinical sample types, and cost-effectiveness. In this 4 year multicentre retrospective observational study, all clinical samples referred for 16S PCR and/or targeted PCR from a laboratory network serving seven London hospitals were identified. Laboratory, clinical, prescribing, and economic variables were analysed. 78/607 samples were 16S PCR positive; pus samples were most frequently positive (29/84; p < 0.0001), and CSF least (8/149; p = 0.003). 210/607 samples had targeted PCR (361 targets requested across 23 organisms) with 43/361 positive; respiratory samples (13/37; p = 0.01) had the highest detection rate. Molecular diagnostics provided a supportive microbiological diagnosis for 21 patients and a new diagnosis for 58. 14/91 patients with prescribing information available and a positive PCR result had antimicrobial de-escalation. For culture-negative samples, mean cost-per-positive 16S PCR result was £568.37 and £292.84 for targeted PCR, equating to £4041.76 and £1506.03 respectively for one prescription change. 16S PCR is more expensive than targeted PCR, with both assisting in microbiological diagnosis but uncommonly enabling antimicrobial change. Rigorous referral pathways for molecular tests may result in significant fiscal savings.
Middle Miocene long-term continental temperature change in and out of pace with marine climate records
Authors: Methner Katharina , Campani Marion , Fiebig Jens , Löffler Niklas , Kempf Oliver , Mulch Andreas 
Published: May 2020

AbstractReconstructing long-term continental temperature change provides the required counterpart to age equivalent marine records and can reveal how terrestrial and marine temperatures were related during times of extreme climate change such as the Miocene Climatic Optimum (MCO) and the following Middle Miocene Climatic Transition (MMCT). Carbonate clumped isotope temperatures (T(Δ47)) from 17.5 to 14.0 Ma Central European paleosols (Molasse Basin, Switzerland) display a temperature pattern during the MCO that is similar to coeval marine temperature records. Maximum temperatures in the long-term soil T(Δ47) record (at 16.5 and 14.9 Ma) lag maximum ocean bottom water temperatures, lead global ice volume, and mark the initiation of minimum global ice volume phases. The suggested onset of the MMCT, deduced by a marked and rapid decline in Molasse Basin soil temperatures is coeval with cooling reported in high-latitudinal marine records. This is best explained by a change in the seasonal timing of soil carbonate formation that was likely driven by a modification of rainfall seasonality and thus by a major reorganization of mid-latitude atmospheric circulation across Central Europe. In particular, our data suggest a strong climate coupling between the North Atlantic and Central Europe already in the middle Miocene.
Longitudinal Study of Oral Microbiome Variation in Twins
Authors: Freire Marcelo , Moustafa Ahmed , Harkins Derek M. , Torralba Manolito G. , Zhang Yun , Leong Pamela , Saffery Richard , Bockmann Michelle , Kuelbs Claire , Hughes Toby , Craig Jeffrey M. , Nelson Karen E. 
Published: May 2020

AbstractHumans are host to a multitude of microorganisms that rapidly populate the body at birth, subject to a complex interplay that is dependent on host genetics, lifestyle, and environment. The host-associated microbiome, including the oral microbiome, presents itself in a complex ecosystem important to health and disease. As the most common chronic disease globally, dental caries is induced by host-microbial dysbiosis in children and adults. Multiple biological and environmental factors are likely to impact disease predisposition, onset, progression, and severity, yet longitudinal studies able to capture these influences are missing. To investigate how host genetics and environment influenced the oral microbial communities over time, we profiled supragingival plaque microbiomes of dizygotic and monozygotic twins during 3 visits over 12-months. Dental plaque DNA samples were amplified by targeting the 16S rRNA gene V4 region, and microbial findings were correlated with clinical, diet and genetic metadata. We observed that the oral microbiome variances were shaped primarily by the environment when compared to host genetics. Among the environmental factors shaping microbial changes of our subjects, significant metadata included age of the subject, and the age by which subjects initiated brushing habits, and the types of actions post-brushing. Relevant heritability of the microbiome included Actinomyces and Capnocytophaga in monozygotic twins and Kingella in dizygotic twins. Corynebacterium and Veillonella abundances were associated with age, whereas Aggregatibacter was associated with younger subjects. Streptococcus abundance showed an inverse association over time, and Selenomonas abundances increased with brushing frequency per day. Unraveling the exact biological mechanisms in caries has the potential to reveal novel host-microbial biomarkers, pathways, and targets important to effective preventive measures, and early disease control in children.
Information Cascades and the Collapse of Cooperation
Authors: Yang Guoli , Csikász-Nagy Attila , Waites William , Xiao Gaoxi , Cavaliere Matteo 
Published: May 2020

AbstractIn various types of structured communities newcomers choose their interaction partners by selecting a role-model and copying their social networks. Participants in these networks may be cooperators who contribute to the prosperity of the community, or cheaters who do not and simply exploit the cooperators. For newcomers it is beneficial to interact with cooperators but detrimental to interact with cheaters. However, cheaters and cooperators usually cannot be identified unambiguously and newcomers’ decisions are often based on a combination of private and public information. We use evolutionary game theory and dynamical networks to demonstrate how the specificity and sensitivity of those decisions can dramatically affect the resilience of cooperation in the community. We show that promiscuous decisions (high sensitivity, low specificity) are advantageous for cooperation when the strength of competition is weak; however, if competition is strong then the best decisions for cooperation are risk-adverse (low sensitivity, high specificity). Opportune decisions based on private and public information can still support cooperation but suffer of the presence of information cascades that damage cooperation, especially in the case of strong competition. Our research sheds light on the way the interplay of specificity and sensitivity in individual decision-making affects the resilience of cooperation in dynamical structured communities.
Accuracy and Effectiveness of Mammography versus Mammography and Tomosynthesis for Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis
Authors: Giampietro Rodrigo Rosa , Cabral Marcos Vinicius Gama , Lima Silvana Andrea Molina , Weber Silke Anna Theresa , dos Santos Nunes-Nogueira Vania 
Published: May 2020

AbstractWe proposed to compare the accuracy and effectiveness of digital breast tomosynthesis (DBT), plus digital or synthetic mammography, with digital mammography alone in women attending population-based breast cancer screenings. We performed a systematic review and included controlled studies comparing DBT with digital mammography for breast cancer screening. Search strategies were applied to the MEDLINE, Embase, LILACS, and CENTRAL databases. With moderate quality of evidence, in 1,000 screens, DBT plus digital mammography increased the overall and invasive breast cancer rates by 3 and 2 (RR 1.36, 95% CI 1.18 to 1.58 and RR 1.51, 95% CI 1.27 to 1.79, respectively). DBT plus synthetic mammography increased both overall and invasive breast cancer rates by 2 (RR 1.38, 95% CI 1.24 to 1.54 and RR 1.37, 95% CI 1.22 to 1.55, respectively). DBT did not improve recall, false positive and false negative rates. However due to heterogeneity the quality of evidence was low. For women attending population-based breast cancer screenings, DBT increases rates of overall and invasive breast cancer. There is no evidence with high or moderate quality showing that DBT compared with digital mammography decreases recall rates, as well as false positive and false negative rates.
The establishment of a fungal consortium in a new winery
Authors: Abdo Hany , Catacchio Claudia Rita , Ventura Mario , D’Addabbo Pietro , Alexandre Hervé , Guilloux-Bénatier Michèle , Rousseaux Sandrine 
Published: May 2020

AbstractThe biodiversity and evolution of fungal communities were monitored over a period of 3 vintages in a new winery. Samples were collected before grape receipt and 3 months after fermentation from 3 different wine related environments (WRE): floor, walls and equipment and analyzed using Illumina Mi-Seq. Genera of mold and filamentous fungi (294), non-enological (10) and wine-associated yeasts (25) were detected on all WREs before the arrival of the first harvest. Among them, genera likeAlternariaandAureobasidiumpersisted during two vintages. Therefore, these genera are not specific to winery environment and appear to be adapted to natural or anthropic environments due to their ubiquitous character. Some genera likeCandidawere also detected before the first harvest but only on one WREs, whereas, on the other WREs they were found after the harvest. The ubiquitous character and phenotypic traits of these fungal genera can explain their dynamics. After the first harvest and during 3 vintages the initial consortium was enriched by oenological genera likeStarmerellaintroduced either by harvest or by potential transfers between the different WREs. However, these establishing genera, includingSaccharomyces, do not appear to persist due to their low adaptation to the stressful conditions of winery environment.
Immunity to vector saliva is compromised by short sand fly seasons in endemic regions with temperate climates
Authors: Oliveira Fabiano , Giorgobiani Ekaterina , Guimarães-Costa Anderson B. , Abdeladhim Maha , Oristian James , Tskhvaradze Lamzira , Tsertsvadze Nikoloz , Zakalashvili Mariam , Valenzuela Jesus G. , Kamhawi Shaden 
Published: May 2020

AbstractIndividuals exposed to sand fly bites develop humoral and cellular immune responses to sand fly salivary proteins. Moreover, cellular immunity to saliva or distinct salivary proteins protects against leishmaniasis in various animal models. In Tbilisi, Georgia, an endemic area for visceral leishmaniasis (VL), sand flies are abundant for a short period of ≤3 months. Here, we demonstrate that humans and dogs residing in Tbilisi have little immunological memory to saliva ofP. kandelakii, the principal vector of VL. Only 30% of humans and 50% of dogs displayed a weak antibody response to saliva after the end of the sand fly season. Likewise, their peripheral blood mononuclear cells mounted a negligible cellular immune response after stimulation with saliva. RNA seq analysis of wild-caughtP. kandelakiisalivary glands established the presence of a typical salivary repertoire that included proteins commonly found in other sand fly species such as the yellow, SP15 and apyrase protein families. This indicates that the absence of immunity toP. kandelakiisaliva in humans and dogs from Tbilisi is probably caused by insufficient exposure to sand fly bites. This absence of immunity to vector saliva will influence the dynamics of VL transmission in Tbilisi and other endemic areas with brief sand fly seasons.