bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Mutations in the Mitochondrial 2-Oxoglutarate/Malate Carrier SLC25A11 Gene Confer a Predisposition to Metastatic Paragangliomas
Authors: Buffet Alexandre , Morin Aurélie , Castro-Vega Luis-Jaime , Habarou Florence , Lussey-Lepoutre Charlotte , Letouzé Eric , Lefebvre Hervé , Guilhem Isabelle , Haissaguerre Magalie , Raingeard Isabelle , Padilla-Girola Mathilde , Tran Thi , Tchara Lucien , Bertherat Jérôme , Amar Laurence , Ottolenghi Chris , Burnichon Nelly , Gimenez-Roqueplo Anne-Paule , Favier Judith 
Published: February 2018

Abstract
Comprehensive genetic analyses have identified germline SDHB and FH gene mutations as predominant causes of metastatic paraganglioma and pheochromocytoma. However, some suspicious cases remain unexplained. In this study, we performed whole-exome sequencing of a paraganglioma exhibiting an SDHx-like molecular profile in the absence of SDHx or FH mutations and identified a germline mutation in the SLC25A11 gene, which encodes the mitochondrial 2-oxoglutarate/malate carrier. Germline SLC25A11 mutations were identified in six other patients, five of whom had metastatic disease. These mutations were associated with loss of heterozygosity, suggesting that SLC25A11 acts as a tumor-suppressor gene. Pseudohypoxic and hypermethylator phenotypes comparable with those described in SDHx- and FH-related tumors were observed both in tumors with mutated SLC25A11 and in Slc25a11Δ/Δ immortalized mouse chromaffin knockout cells generated by CRISPR-Cas9 technology. These data show that SLC25A11 is a novel paraganglioma susceptibility gene for which loss of function correlates with metastatic presentation.
Significance: A gene encoding a mitochondrial carrier is implicated in a hereditary cancer predisposition syndrome, expanding the role of mitochondrial dysfunction in paraganglioma. Cancer Res; 78(8); 1914–22. ©2018 AACR.
Foretinib Overcomes Entrectinib Resistance Associated with the NTRK1 G667C Mutation in NTRK1 Fusion–Positive Tumor Cells in a Brain Metastasis Model
Authors: Nishiyama Akihiro , Yamada Tadaaki , Kita Kenji , Wang Rong , Arai Sachiko , Fukuda Koji , Tanimoto Azusa , Takeuchi Shinji , Tange Shoichiro , Tajima Atsushi , Furuya Noritaka , Kinoshita Takayoshi , Yano Seiji 
Published: February 2018

Abstract
Purpose: Rearrangement of the neurotrophic tropomyosin receptor kinase 1 (NTRK1) gene, which encodes tyrosine receptor kinase A (TRK-A), occurs in various cancers, including colon cancer. Although entrectinib is effective in the treatment of central nervous system (CNS) metastases that express NTRK1 fusion proteins, acquired resistance inevitably results in recurrence. The CNS is a sanctuary for targeted drugs; however, the mechanism by which CNS metastases become entrectinib-resistant remains elusive and must be clarified to develop better therapeutics.
Experimental Design: The entrectinib-resistant cell line KM12SM-ER was developed by continuous treatment with entrectinib in the brain metastasis–mimicking model inoculated with the entrectinib-sensitive human colon cancer cell line KM12SM, which harbors the TPM3-NTRK1 gene fusion. The mechanism of entrectinib resistance in KM12SM-ER cells was examined by next-generation sequencing. Compounds that overcame entrectinib resistance were screened from a library of 122 kinase inhibitors.
Results: KM12SM-ER cells, which showed moderate resistance to entrectinib in vitro, had acquired the G667C mutation in NTRK1. The kinase inhibitor foretinib inhibited TRK-A phosphorylation and the viability of KM12SM-ER cells bearing the NTRK1-G667C mutation in vitro. Moreover, foretinib markedly inhibited the progression of entrectinib-refractory KM12SM-ER–derived liver metastases and brain tumors in animal models, predominantly through inhibition of TRK-A phosphorylation.
Conclusions: These results suggest that foretinib may be effective in overcoming entrectinib resistance associated with the NTRK1-G667C mutation in NTRK1 fusion–positive tumors in various organs, including the brain, and provide a rationale for clinical trials of foretinib in cancer patients with entrectinib-resistant tumors harboring the NTRK1-G667C mutation, including patients with brain metastases. Clin Cancer Res; 24(10); 2357–69. ©2018 AACR.
Re-viewing William Blake’s Paradise Regained (c. 1816–1820)
Authors: Billingsley Naomi 
Published: February 2018

Abstract
This article presents a revisionist reading of William Blake’s (1757–1827) twelve watercolor designs for John Milton’s “Paradise Regained” (c. 1816–1820). The designs have previously been dismissed in critical commentary as of little interest to Blake scholarship, or regarded as a narrative merely about Christ’s human nature. This article argues that they are also a visual expression of Blake’s cosmology; it is proposed that the designs express a positive cosmology, in which Paradise is not so much to be regained, as re-viewed. The article argues that Blake emphasizes Christ’s divinity in the designs and that he is depicted as an immanent, sacramental presence in the world; hence, the world that Christ inhabits in the designs is a Paradise. The article begins by outlining its reading of Blake’s view of the material world, and moves on to discuss the “Paradise Regained” designs in detail, with a particular focus on The Baptism of Christ, the opening subject of the series, which establishes the positive cosmology presented throughout the series.
Paradise City
Authors: Coltrin Chris 
Published: February 2018

Abstract
In a century defined by the rise of cities, the early nineteenth-century painter John Martin broke artistic precedents and represented heavenly Paradise as a space premised on urban living. Though he did not entirely reject the more traditional conception of Paradise as a garden, he merged the rural vision of Paradise with urban structures and spaces. Martin’s widespread popularity, combined with the contentious discourses regarding the nature of the city, ensured that his representations engaged a set of public debates regarding the nature of urban life in profound ways. Martin’s paintings and prints suggested that God not only tolerates cities, but that God builds them and resides in them. In essence, his paintings and prints revealed an urban heaven that helped make a political and religious case for urban life in general.
Spires and Cathedrals
Authors: Heitschmidt Gregg 
Published: February 2018

Abstract
In the latter half of the nineteenth century, especially between 1859 and 1872, Union officers and enlisted men, scientists and explorers, artists and writers traveled westward. Surveyors appraised and mapped; expeditionary members explored and then wrote, hoping to convey the wonders they had witnessed. The western wilderness was an enormous expanse, one that as easily represented commercial possibilities as it did a new ideal. Nevertheless, the western wilderness also mesmerized and inspired, provoking a type of awe and wonderment in its languorous canyons, exploding fumaroles, bubbling hot springs, and soaring granite spires. From the Rockies to the Sawtooths, from the Cascades to the Tetons, the mountains of the American West mystified and hypnotized those who saw them. The Sierra Nevadas, in particular, became the locus for artists and writers. Their paintings and publications, in turn, inspired entire groups to travel to the Yosemite Valley in order to ponder the sublime beauties of Nature found there. Through the paintings and sketches of Albert Bierstadt and Thomas Moran, and through the meticulous journal entries and travel narratives of Clarence King and John Muir—whose work as a Naturalist eventually helped establish the Valley as a National Park—Yosemite captured the imagination of the American people, as its spires, cliffs, and waterfalls had been artistically transformed from mere tourist destinations into sites of divine revelation.
Found or Recovered?
Authors: Weichbrodt Elissa Yukiko 
Published: February 2018

Abstract
In the 1880s, American artists Charles Furneaux, Joseph D. Strong, and Jules Tavernier—who later became known as the “Volcano School”—traveled to the Kingdom of Hawai‘i and produced dozens of landscapes ranging from otherworldly scenes of volcanoes to vistas of untouched, pristine beaches. While white, upper-class landowners in Hawai‘i served as the primary patrons of such paintings, the reigning monarch, King David Kalākaua, also commissioned his own sweeping landscapes from the same artists. This article focuses on the two competing narratives of paradise at work in both these paintings and writings about the Hawaiian Islands in the 1880s. “Paradise” could invoke a Romantic position, one that celebrated the landscape’s wildness and equated nature in its pure state with the lost Garden of Eden. On the other hand, Kalākaua’s commissions reflect what environmental historian Carolyn Merchant calls the Recovery Narrative: a story of humans reversing the effects of the biblical Fall by subjugating desolate and distant wilds and transforming them into fruitful lands. This article argues that Kalākaua’s presentation of “paradise” was part of a multi-pronged but ultimately failed strategy to resist American imperialism and present the Kingdom of Hawai‘i to the West as a prosperous, profitable nation.
Themes of Paradise in Contemporary British and American Art
Authors: Romaine James 
Published: February 2018

Abstract
The idea of paradise has inspired the artistic imagination in, at least, two directions. One is an impulse to create a more perfect tomorrow by addressing social ills today. The other is sometimes manifest in a desire to recover a lost spiritual consciousness or creative imagination. These directions are evidenced in the work of two contemporary artists. In an exhibition entitled Tomorrow is Another Day, created for the 2017 Venice Biennale, Los Angeles-based artist Mark Bradford draws the viewer toward an imagined social horizon, beyond which dawns a more perfect world. Simultaneously on view in Venice, but not a part of the Biennale, Damien Hirst’s Treasures from the Wreck of the Unbelievable explores a rapacious hunger for immortality. Purporting to be the salvage of an ancient shipwreck, Hirst’s exhibition tests the modern, post-enlightenment, viewer’s willingness, even ability, to believe.
Nicotiana benthamiana as model plant for Meloidogyne graminicola infection
Authors: Naalden Diana , Verbeek Ruben , Gheysen Godelieve 
Published: February 2018

Summary
Nicotiana benthamiana is widely used as a model plant to analyse cell biology and to obtain insight into the molecular host-pathogen interaction because it is susceptible to many pathogens. Since N. benthamiana can be transformed easily, it is also used to study pathogens for which it is not a known host. Meloidogyne graminicola has a fairly broad host range of mainly monocots and some dicots but no data were available on the ability of M. graminicola to infect N. benthamiana. In this study, we show that M. graminicola is able to infect and complete its life cycle in N. benthamiana, although our experiments demonstrate a lower susceptibility compared to rice. In addition, M. graminicola was also able to develop in N. tabacum but the reproduction was very low. Therefore, we conclude that N. benthamiana can be considered as a host, while this is not the case for N. tabacum.
The ‘Bad Global Citizen’, ‘Naked’, in the ‘Transnational Penal Space’
Authors: Boister Neil 
Published: February 2018

Abstract
This article explores how transnational criminal law is used as a tool to create a legal space within the state where the fugitive resides or is acting, in order in effect to re-set the border inside that jurisdiction and to make it possible, by proxy, to enforce another state’s law. It argues that transnational criminal law is used to establish a kind of fictional transnational legal space, created by changing domestic laws and practices of both the state exercising its jurisdiction and the state in which that jurisdiction is being exercised, so that restrictions on cooperative action are minimalized. It explores how that space is created and how it shapes the structure of transnational criminal law through the building of normative structures—both legal and administrative—to suppress the activities of alleged criminals in this space. But its specific focus is on how this purely functional relationship impacts on individuals caught within that space.
Hybridity and integration in local collective action: an analytical framework
Authors: Divay Gérard , Slimani Youssef 
Published: February 2018

Can an integrated territorial approach successfully do away with the silo structure that marks public action through the hybridisation of sectoral logics? Drawing from various strands of research, as well as an assessment of multiple studies on the impact of integrated territorial approaches on local social development, this article develops an analytical framework to address this question. We argue that integration takes place according to four regimes, whose dynamics range from the simple juxtaposition of sectoral organisations to a hybridisation of their organisational logics. The regimes we identify are operational networking, interstitial effervescence, collaborative accommodation and institutional convergence. Each emerges from an interaction between the specific dynamics of each experience in a given milieu and supra-local socio-institutional processes, which generate new ways of conceiving and organising the coordination of public and collective action at the local level. Points for practitioners This article puts into perspective the virtues of the integrated approach as an antidote to public administration silos. An integrated approach to local action only produces the expected effects if each public agency agrees to transform its organisational culture and to direct its action according to the evolution of local ecosystem processes of change in the milieu as a whole.
Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies
Authors: Cheraghlou Shayan , Otremba Michael , Kuo Yu Phoebe , Agogo George O. , Hersey Denise , Judson Benjamin L. 
Published: February 2018

ObjectiveStudies have suggested that the lymph node yield and lymph node density from selective or elective neck dissections are predictive of patient outcomes and may be used for patient counseling, treatment planning, or quality measurement. Our objective was to systematically review the literature and conduct a meta‐analysis of studies that investigated the prognostic significance of lymph node yield and/or lymph node density after neck dissection for patients with head and neck cancer.Data SourcesThe Ovid/Medline, Ovid/Embase, and NLM PubMed databases were systematically searched on January 23, 2017, for articles published between January 1, 1946, and January 23, 2017.Review MethodsWe reviewed English‐language original research that included survival analysis of patients undergoing neck dissection for a head and neck malignancy stratified by lymph node yield and/or lymph node density. Study data were extracted by 2 independent researchers (S.C. and M.O.). We utilized the DerSimonian and Laird random effects model to account for heterogeneity of studies.ResultsOur search yielded 350 nonduplicate articles, with 23 studies included in the final synthesis. Pooled results demonstrated that increased lymph node yield was associated with a significant improvement in survival (hazard ratio, 0.833; 95% CI, 0.790‐0.879). Additionally, we found that increased lymph node density was associated with poorer survival (hazard ratio, 1.916; 95% CI, 1.637‐2.241).ConclusionsIncreased nodal yield portends improved outcomes and may be a valuable quality indicator for neck dissections, while increased lymph node density is associated with diminished survival and may be used for postsurgical counseling and planning for adjuvant therapy.
High doses of minocycline may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction
Authors: Li Wenyao , Chai Qing , Zhang Hongwei , Ma Jing , Xu Chengfen , Dong Jifu , Wei Xianghua , Wang Zhiyi , Zhang Kexian 
Published: February 2018

Objective Postoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1 day, 3 days, and 7 days after surgery, and microglial activation was measured at 3 hours and 7 days after surgery. Memory was assessed using the Morris water maze test. Results Surgery resulted in severe cognitive impairment in aged rats and induced a significant neuroinflammatory response and microglial activation. The use of minocycline can prevent microglial activation after surgery, but delayed microglial activation may occur. The use of minocycline may further impair memory after surgery. Conclusion Minocycline can restrain microglial activation and restrict the inflammatory response in the hippocampus early after surgery, but it may induce delayed microglial activation and cannot prevent POCD in aged rats.
The Impact of Implementing an Intensivist Model With Nighttime In-Hospital Nocturnist and Effect on ICU Outcomes
Authors: Tanios Maged A. , Teres Daniel , Park Hyunsoon , Beltran Antonio , Sehgal Arunpal , Leo James D. 
Published: February 2018

Background: Various intensivist staffing models have been suggested, but the long-term sustainability and outcomes vary and may not be sustained. We examined the impact of implementing a high-intensity intensivist coverage model with a nighttime in-house nocturnist (non-intensivist) and its effect on intensive care unit (ICU) outcomes. Methods: We obtained historical control baseline data from 2007 to 2011 and compared the same data from 2011 to 2015. The Acute Physiological and Chronic Health Evaluation outcomes system was utilized to collect clinical, physiological, and outcome data on all adult patients in the medical ICU and to provide severity-adjusted outcome predictions. The model consists of a mandatory in-house daytime intensivist service that leads multidisciplinary rounds, and an in-house nighttime coverage is provided by nocturnist (nonintensivists) with current procedural skills in airways management, vascular access, and commitment to supervise house staff as needed. The intensivist continues to be available remotely at nighttime for house staff and consultation with the nocturnist. A backup intensivist is available for surge management. Results: First year yielded improved throughput (2428 patients/year to 2627 then 2724 at fifth year). Case mix stable at 53.7 versus 55.2. The ICU length of stay decreased from 4.7 days (predicted 4.25 days) to 3.8 days (4.15) in first year; second year: 3.63 days (4.29 days); third year: 3.24 days (4.37), fourth year: 3.34 days (4.45), and fifth year: 3.61 days (4.42). Intensive care unit <24 hours readmission remained at 1%; >24 hours increased from 4% to 6%. Low-risk monitoring admissions remained at an average 17% (benchmark 17.18%). Intensive care unit mortality improved with standardized mortality ration averaging at 0.84. Resident satisfaction surveys improved. Conclusions: Implementing an intensivist service with nighttime nocturnist staffing in a high-intensity large teaching hospital is feasible and improved ICU outcomes in a sustained manner that persisted after the initial implementation phase. The model resulted in reduced and sustained observed-to-predicted length of ICU stay.
Maternal Perceptions of Infant Feeding and Health in the Context of the 2015 Nepal Earthquake
Authors: DeYoung Sarah , Suji Manoj , Southall Hannah G. 
Published: February 2018

Background: Displacement caused by the 2015 earthquake in Nepal exacerbated poor health and nutrition for thousands of women and children. Research aim: This study aimed to identify the perceptions of Nepalese mothers residing in earthquake relocation camps regarding barriers, facilitators, and situational factors influencing breastfeeding and family well-being. Methods: An exploratory, rapid ethnographic approach was used during two fieldwork phases. Phase 1 consisted of reconnaissance and observation, whereas Phase 2 consisted of observation and qualitative semistructured interviews with infant caretakers ( N = 14). Results: We found evidence of human milk substitutes donated by various groups after the earthquake, despite Nepal’s media statement condemning these donations. Participants in this study expressed concerns about their milk supply. They also expressed concerns about the impending winter season combined with distress about the 2015 fuel crisis and the impact that this had on their infants and children. Furthermore, participants expressed choices about infant feeding that were influenced by traditional Nepalese practices. Specifically, homemade complementary foods and spices designed to boost lactation were identified as being used during daily infant feeding practices. Conclusion: Infant caretakers need culturally specific support for breastfeeding after disasters. These findings can directly influence future interventions concerning Nepalese mothers’ perceptions, infant care, and feeding practices in disaster scenarios.
Comparison between disease onset patterns of Egyptian juvenile and adult systemic lupus erythematosus (single centre experience)
Authors: Abdel-Nabi H H , Abdel-Noor R A 
Published: February 2018

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that occurs worldwide in both children and adults, with different disease manifestations, activity and severity between them. Objectives To analyse the difference in disease onset patterns and activity in Egyptian children and adults with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (≤18 years). Disease onset, clinical manifestations and laboratory investigations were recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was used to assess disease onset activity; renal biopsy was performed for all cases affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean age 29.65 ± 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis 12.63 ± 3.112 years. The most frequent initial a-SLE symptoms were constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central nervous system (11.6%). There were no significant differences between a-SLE and j-SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but the j-SLE haematological (88%) and central nervous system (30.1%) manifestations were significantly higher than a-SLE and articular manifestations were significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7% a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23 ± 4.966 in a-SLE and was significantly higher in j-SLE (27.13 ± 19.968). International Society of Nephrology lupus nephritis classes III and IV (42.4%) were the commonest findings in a-SLE; however, classes I and III (57.9%) were the commonest in j-SLE. Conclusions SLE had a wide variety of clinical and immunological manifestations, with some similarity and differences between a-SLE and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial manifestations than a-SLE.