bluuebunny/crossref_metadata_2025_split huggingface dataset:
Science with the Murchison Widefield Array: Phase I results and Phase II opportunities
Authors: Beardsley A. P. , Johnston-Hollitt M. , Trott C. M. , Pober J. C. , Morgan J. , Oberoi D. , Kaplan D. L. , Lynch C. R. , Anderson G. E. , McCauley P. I. , Croft S. , James C. W. , Wong O. I. , Tremblay C. D. , Norris R. P. , Cairns I. H. , Lonsdale C. J. , Hancock P. J. , Gaensler B. M. , Bhat N. D. R. , Li W. , Hurley-Walker N. , Callingham J. R. , Seymour N. , Yoshiura S. , Joseph R. C. , Takahashi K. , Sokolowski M. , Miller-Jones J. C. A. , Chauhan J. V. , Bojičić I. , Filipović M. D. , Leahy D. , Su H. , Tian W. W. , McSweeney S. J. , Meyers B. W. , Kitaeff S. , Vernstrom T. , Gürkan G. , Heald G. , Xue M. , Riseley C. J. , Duchesne S. W. , Bowman J. D. , Jacobs D. C. , Crosse B. , Emrich D. , Franzen T. M. O. , Horsley L. , Kenney D. , Morales M. F. , Pallot D. , Steele K. , Tingay S. J. , Walker M. , Wayth R. B. , Williams A. , Wu C. 
Published: December 2019

AbstractThe Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together$60+$programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Condensed tannins decreased the growth performance and impaired intestinal immune function in on-growing grass carp (Ctenopharyngodon idella)
Authors: Li Mei , Feng Lin , Jiang Wei-Dan , Wu Pei , Liu Yang , Jiang Jun , Kuang Sheng-Yao , Tang Ling , Zhou Xiao-Qiu 
Published: December 2019

AbstractThe present study investigated the effects of condensed tannins (CT) on intestinal immune function in on-growing grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp were fed six diets containing different levels of CT (0, 10·00, 20·00, 30·00, 40·00 and 50·00 g/kg diet) for 70 d and then challenged with Aeromonas hydrophila for 14 d. The results showed that, compared with the control group, dietary CT (1) induced intestinal histopathological lesions and aggravated enteritis; (2) decreased lysozyme and acid phosphatase activities, complement 3 (C3), C4 and IgM contents and down-regulated the Hepcidin, liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, Mucin2 and β-defensin-1 mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) (P < 0·05); (3) down-regulated the mRNA levels of anti-inflammatory cytokines transforming growth factor (TGF)-β1, TGF-β2 (not in MI and DI), IL-4/13A (not IL-4/13B), IL-10 and IL-11 partly correlated with target of rapamycin (TOR) signalling; and (4) up-regulated the mRNA levels of pro-inflammatory cytokines interferon-γ2, IL-1β, IL-6, IL-8 (not in PI), IL-12p35, IL-12p40, IL-15 and IL-17D partly related to NF-κB signalling in the intestine of on-growing grass carp. Overall, the results indicated that CT could impair the intestinal immune function, and its potential regulation mechanisms were partly associated with the TOR and NF-κB signalling pathways. Finally, based on the percentage weight gain and enteritis morbidity, the maximum allowable levels of CT for on-growing grass carp (232·22–890·11 g) were estimated to be 18·6 and 17·4 g/kg diet, respectively.
Party Institutionalization and Welfare State Development
Authors: Rasmussen Magnus B. , Knutsen Carl Henrik 
Published: December 2019

AbstractThis article argues that the extent to which political parties are institutionalized shapes welfare state development. Institutionalized parties allow politicians to overcome co-ordination problems, avoid capture by special interests and form stable linkages with broad social groups. These features both enable and incentivize politicians to pursue extensive welfare policies. The study employs measures of party institutionalization and welfare state features to study these proposed relationships. Even when accounting for country- and year-fixed effects and plausible confounders such as electoral system, unionization, regime type and state capacity, the authors find clear relationships between party institutionalization and more extensiveanduniversal welfare states. Focusing on universalism, they find that the relationship is more pronounced when constraints on executives are strong and in democracies, but that it also exists in autocracies. Further, when disaggregating party institutionalization and evaluating mechanisms, the linkages that institutionalized parties form with social groups constitute one important, but not the only relevant, factor.
CD14+monocytes are the main leucocytic sources of CXCL10 in response toPlasmodium falciparum
Authors: Ioannidis Lisa J. , Eriksson Emily , Hansen Diana S. 
Published: December 2019

AbstractThe CXCR3 chemokine CXCL10 or IFN-γinducible protein 10 (IP-10) has been identified as an important biomarker of cerebral malaria (CM) mortality in children. Studies in mouse malaria infection models have shown that CXCL10 blockade alleviates brain intravascular inflammation and protects infected mice from CM. Despite the key role that CXCL10 plays in the development of CM, the leucocytic sources of CXCL10 in response to human malaria are not known. Here we investigated CXCL10 responses toPlasmodium falciparumin peripheral blood mononuclear cells (PBMCs). We found that PBMCs from malaria-unexposed donors produce CXCL10 in response toP. falciparumand that this response is IFN-γ-dependent. Moreover, CD14+monocytes were identified as the main leucocytic sources of CXCL10 in peripheral blood, suggesting an important role for innate immune responses in the activation of this pathway involved in the development of symptomatic malaria.
An evidence-based framework for identifying technologies of no or low-added value (NLVT)
Authors: Esandi María Eugenia , Gutiérrez-Ibarluzea Iñaki , Ibargoyen-Roteta Nora , Godman Brian 
Published: December 2019

ObjectiveTo synthetize the state of the art of methods for identifying candidate technologies for disinvestment and propose an evidence-based framework for executing this task.MethodsAn interpretative review was conducted. A systematic literature search was performed to identify secondary or tertiary research related to disinvestment initiatives and/or any type of research that specifically described one or more methods for identifying potential candidates technologies, services, or practices for disinvestment. An iterative and critical analysis of the methods described alongside the disinvestment initiatives was performed.ResultsSeventeen systematic reviews on disinvestment or related terms (health technology reassessment or medical reversal) were retrieved and methods of 45 disinvestment initiatives were compared. On the basis of this evidence, we proposed a new framework for identifying these technologies based on the wide definition of evidence provided by Lomas et al. The framework comprises seven basic approaches, eleven triggers and thirteen methods for applying these triggers, which were grouped in embedded and ad hoc methods.ConclusionsAlthough identification methods have been described in the literature and tested in different contexts, the proliferation of terms and concepts used to describe this process creates considerable confusion. The proposed framework is a rigorous and flexible tool that could guide the implementation of strategies for identifying potential candidates for disinvestment.
Characterisation of community-acquired Staphylococcus aureus causing skin and soft tissue infections in a children's hospital in Shanghai, China
Authors: Wang Xing , Shen Yanyun , Huang Weichun , Zhou Yun 
Published: December 2019

Abstract
Community-acquired Staphylococcus aureus is a major pathogen responsible for skin and soft tissue infections (SSTIs). This study aimed to investigate the prevalence and molecular characteristics of community-acquired S. aureus isolates recovered from paediatric patients with SSTIs in Shanghai, China. Between January 2015 and January 2018, 91 community-acquired S. aureus isolates were characterised by antibiotic susceptibility, multilocus sequence typing (ST), staphylococcal protein A gene (spa) type and virulence genes. Methicillin-resistant S. aureus (MRSA) strains were also characterised by staphylococcal cassette chromosome mec (SCCmec) type. Forty-one (45.1%) S. aureus isolates were MRSA. ST59 (33.0%, 30/91) was the most common sequence type, and t437 (18.7%, 17/91) was the most common spa type. SCCmec IV and V accounted for 61.0% and 34.1% of all MRSA isolates, respectively. Each isolate carried at least six virulence genes. The positive rates of Panton-Valentine leukocidin genes among all S. aureus, MRSA and methicillin-susceptible S. aureus isolates were 30.8% (28/91), 39.0% (16/41) and 24% (12/50), respectively. The prevalence of community-associated MRSA was surprisingly high among children with community-acquired SSTIs in Shanghai. ST59-t437 was the most prevalent community-acquired S. aureus clone causing SSTIs.
America First, Immigrants Last: American Xenophobia Then and Now
Authors: Lee Erika 
Published: December 2019

AbstractGlobal mass migration was one of the most defining features of the Gilded Age and the Progressive Era. But so was intense xenophobia. This article offers a new definition of xenophobia and examines how xenophobia helped to drive some of the most defining features of the Gilded Age and the Progressive Era, including progressive reform, white supremacy, the expanded capacity and power of the nation-state, and the growth of U.S. global power and influence. It draws a connection to contemporary America, where, under the Trump administration, xenophobia is transforming a wide range of public policies, legitimizing racism and white supremacy, and impacting U.S. foreign relations.
The Roles of Mineral Dust as Cloud Condensation Nuclei and Ice Nuclei During the Evolution of a Hail Storm
Authors: Chen Qian , Yin Yan , Jiang Hui , Chu Zhigang , Xue Lulin , Shi Rulin , Zhang Xin , Chen Jinghua 
Published: December 2019

AbstractAerosols play important roles in the evolution of deep convective systems like hailstorms. In this study, the heterogeneous ice nucleation schemes have been improved in the Weather Research and Forecasting model coupled with a spectral bin microphysics (WRF‐SBM), which considered aerosols acting as ice nuclei (IN). A hail storm occurred around Tianshan mountains, northwestern China, was simulated with updated WRF‐SBM, and the results have been compared with satellite observations. Further, four sensitive simulation tests were conducted with different cloud condensation nuclei (CCN) and IN concentrations to investigate their respective roles during the evolution of the hailstorm. The increase in CCN concentration resulted in larger cloud droplet concentration and cloud water content, as well as enhanced condensational growth, which released more latent heat and led to stronger updraft at lower levels. The increase in IN number almost did not affect warm processes but led to larger ice crystal concentration and enhanced Bergeron process. Larger CCN concentration led to larger supercooled liquid water content, which in turn contributed to the enhanced hail growth by more efficient drop‐ice collisions and led to larger size of hail particles, while larger IN number reduced the size of graupel and suppressed the growth of hailstones. An analysis of the mobility of hail indicated increased frequency of larger hail with stronger sedimentation induced by more CCN. A further three ensemble runs with random perturbations on initial temperature and humidity were performed for each aerosol scenario, and the results suggested the robustness of simulated CCN and IN effects.
The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest
Authors: Pichard Alexandre , Marcatili Sara , Karam Jihad , Constanzo Julie , Ladjohounlou Riad , Courteau Alan , Jarlier Marta , Bonnefoy Nathalie , Patzke Sebastian , Stenberg Vilde , Coopman Peter , Cartron Guillaume , Navarro-Teulon Isabelle , Repetto-Llamazares Ada , Heyerdahl Helen , Dahle Jostein , Bardiès Manuel , Pouget Jean-Pierre 
Published: December 2019

AbstractSome patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (177Lu)-lilotomab (Betalutin®) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts,177Lu-lilotomab significantly delayed tumor growth, even at low activity (100 MBq/kg). In athymic mice bearing OCI-Ly8 (diffuse large B-cell lymphoma, DLBCL) or Ramos (Burkitt’s lymphoma) cell xenografts,177Lu-lilotomab activity had to be increased to 500 MBq/kg to show a significant tumor growth delay. Clonogenic and proliferation assays showed that DOHH2 cells were highly sensitive to177Lu-lilotomab, while Ramos cells were the least sensitive, and U2932 (DLBCL), OCI-Ly8, and Rec-1 (mantle cell lymphoma) cells displayed intermediate sensitivity. The strong177Lu-lilotomab cytotoxicity observed in DOHH2 cells correlated with reduced G2/M cell cycle arrest, lower WEE-1- and MYT-1-mediated phosphorylation of cyclin-dependent kinase-1 (CDK1), and higher apoptosis. In agreement,177Lu-lilotomab efficacy in vitro, in vivo, and in patient samples was increased when combined with G2/M cell cycle arrest inhibitors (MK-1775 and PD-166285). These results indicate that177Lu-lilotomab is particularly efficient in treating tumors with reduced inhibitory CDK1 phosphorylation, such as transformed FL.
Peptides encoded by noncoding genes: challenges and perspectives
Authors: Wang Shuo , Mao Chuanbin , Liu Shanrong 
Published: December 2019

AbstractIn recent years, noncoding gene (NCG) translation events have been frequently discovered. The resultant peptides, as novel findings in the life sciences, perform unexpected functions of increasingly recognized importance in many fundamental biological and pathological processes. The emergence of these novel peptides, in turn, has advanced the field of genomics while indispensably aiding living organisms. The peptides from NCGs serve as important links between extracellular stimuli and intracellular adjustment mechanisms. These peptides are also important entry points for further exploration of the mysteries of life that may trigger a new round of revolutionary biotechnological discoveries. Insights into NCG-derived peptides will assist in understanding the secrets of life and the causes of diseases, and will also open up new paths to the treatment of diseases such as cancer. Here, a critical review is presented on the action modes and biological functions of the peptides encoded by NCGs. The challenges and future trends in searching for and studying NCG peptides are also critically discussed.
NBS1 interacts with HP1 to ensure genome integrity
Authors: Bosso Giuseppe , Cipressa Francesca , Moroni Maria Lina , Pennisi Rosa , Albanesi Jacopo , Brandi Valentina , Cugusi Simona , Renda Fioranna , Ciapponi Laura , Polticelli Fabio , Antoccia Antonio , di Masi Alessandra , Cenci Giovanni 
Published: December 2019

AbstractHeterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). In addition, loss of any of the MRN members reduces HP1a levels indicating that the MRN complex acts as regulator of HP1a stability. Moreover, overexpression of HP1a in nbs (but not in rad50 or mre11) mutant cells drastically reduces DNA damage associated with the loss of Nbs suggesting that HP1a and Nbs work in concert to maintain chromosome integrity in flies. We have also found that human HP1α and NBS1 interact with each other and that, similarly to Drosophila, siRNA-mediated inhibition of NBS1 reduces HP1α levels in human cultured cells. Surprisingly, fibroblasts from Nijmegen Breakage Syndrome (NBS) patients, carrying the 657del5 hypomorphic mutation in NBS1 and expressing the p26 and p70 NBS1 fragments, accumulate HP1α indicating that, differently from NBS1 knockout cells, the presence of truncated NBS1 extends HP1α turnover and/or promotes its stability. Remarkably, an siRNA-mediated reduction of HP1α in NBS fibroblasts decreases the hypersensitivity to irradiation, a characteristic of the NBS syndrome. Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
Extracellular vesicle (EV)-polyphenol nanoaggregates for microRNA-based cancer diagnosis
Authors: Jang Minjeong , Choi Giwoong , Choi Yoon Young , Lee Jae Eun , Jung Jik-Han , Oh Seung Won , Han Dai Hoon , Lee Haeshin , Park Ji-Ho , Cheong Jae-Ho , Kim Pilnam 
Published: December 2019

AbstractSmall extracellular vesicles (EVs), including exosomes, in body fluids have important applications in the noninvasive liquid biopsy-based diagnosis of cancer. Current EV-based diagnostic techniques still face practical challenges, such as inefficient EV isolation. Here, we report an efficient, resource-free pre-enrichment approach using (–)-epigallocatechin-3-gallate (EGCG), a polyphenolic biomolecule, to isolate and detect exosomal microRNAs (miRNAs) in human blood plasma samples. Our system comprises three steps: (1) EGCG-mediated EV aggregation, (2) filter-based EV isolation, and (3) molecular beacon-based detection of target miRNA in EVs. Using blood samples from cancer patients with gastric cancer or hepatocellular carcinoma, we constructed an EGCG-assisted miRNA diagnostic system. For both cancers, the levels of target miRNAs (miR-21, -27a, and -375) in EVs were strongly correlated with those in the publicly available GEO database. Our approach, an easy-to-use method for efficient EV isolation and the detection of miRNA in clinical samples, is applicable for molecular diagnostics in precision medicine.
Comparative analysis of squamate brains unveils multi-level variation in cerebellar architecture associated with locomotor specialization
Authors: Macrì Simone , Savriama Yoland , Khan Imran , Di-Poï Nicolas 
Published: December 2019

AbstractEcomorphological studies evaluating the impact of environmental and biological factors on the brain have so far focused on morphology or size measurements, and the ecological relevance of potential multi-level variations in brain architecture remains unclear in vertebrates. Here, we exploit the extraordinary ecomorphological diversity of squamates to assess brain phenotypic diversification with respect to locomotor specialization, by integrating single-cell distribution and transcriptomic data along with geometric morphometric, phylogenetic, and volumetric analysis of high-definition 3D models. We reveal significant changes in cerebellar shape and size as well as alternative spatial layouts of cortical neurons and dynamic gene expression that all correlate with locomotor behaviours. These findings show that locomotor mode is a strong predictor of cerebellar structure and pattern, suggesting that major behavioural transitions in squamates are evolutionarily correlated with mosaic brain changes. Furthermore, our study amplifies the concept of ‘cerebrotype’, initially proposed for vertebrate brain proportions, towards additional shape characters.
Conformational pathway provides unique sensitivity to a synaptic mGluR
Authors: Habrian Chris H. , Levitz Joshua , Vyklicky Vojtech , Fu Zhu , Hoagland Adam , McCort-Tranchepain Isabelle , Acher Francine , Isacoff Ehud Y. 
Published: December 2019

AbstractMetabotropic glutamate receptors (mGluRs) are dimeric G-protein–coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity ~4000-fold lower than other mGluRs and a maximal activation of only ~10%, seemingly too low for activation at synapses. However, mGluR7 heterodimerizes, and we find it to associate with mGluR2 in the hippocampus. Strikingly, the mGluR2/7 heterodimer has high affinity and efficacy. mGluR2/7 shows cooperativity in which an unliganded subunit greatly enhances activation by agonist bound to its heteromeric partner, and a unique conformational pathway to activation, in which mGluR2/7 partially activates in the Apo state, even when its LBDs are held open by antagonist. High sensitivity and an unusually broad dynamic range should enable mGluR2/7 to respond to both glutamate transients from nearby release and spillover from distant synapses.
Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4
Authors: Wang Zhiyong , Wu Victoria H. , Allevato Michael M. , Gilardi Mara , He Yudou , Luis Callejas-Valera Juan , Vitale-Cross Lynn , Martin Daniel , Amornphimoltham Panomwat , Mcdermott James , Yung Bryan S. , Goto Yusuke , Molinolo Alfredo A. , Sharabi Andrew B. , Cohen Ezra E. W. , Chen Qianming , Lyons J. Guy , Alexandrov Ludmil B. , Gutkind J. Silvio 
Published: December 2019

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC.