bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia
Authors: McRae Helen M. , Garnham Alexandra L. , Hu Yifang , Witkowski Matthew T. , Corbett Mark A. , Dixon Mathew P. , May Rose E. , Sheikh Bilal N. , Chiang William , Kueh Andrew J. , Nguyen Tan A. , Man Kevin , Gloury Renee , Aubrey Brandon J. , Policheni Antonia , Di Rago Ladina , Alexander Warren S. , Gray Daniel H. D. , Strasser Andreas , Hawkins Edwin D. , Wilcox Stephen , Gécz Jozef , Kallies Axel , McCormack Matthew P. , Smyth Gordon K. , Voss Anne K. , Thomas Tim 
Published: February 2019

Abstract
Somatically acquired mutations in PHF6 (plant homeodomain finger 6) frequently occur in hematopoietic malignancies and often coincide with ectopic expression of TLX3. However, there is no functional evidence to demonstrate whether these mutations contribute to tumorigenesis. Similarly, the role of PHF6 in hematopoiesis is unknown. We report here that Phf6 deletion in mice resulted in a reduced number of hematopoietic stem cells (HSCs), an increased number of hematopoietic progenitor cells, and an increased proportion of cycling stem and progenitor cells. Loss of PHF6 caused increased and sustained hematopoietic reconstitution in serial transplantation experiments. Interferon-stimulated gene expression was upregulated in the absence of PHF6 in hematopoietic stem and progenitor cells. The numbers of hematopoietic progenitor cells and cycling hematopoietic stem and progenitor cells were restored to normal by combined loss of PHF6 and the interferon α and β receptor subunit 1. Ectopic expression of TLX3 alone caused partially penetrant leukemia. TLX3 expression and loss of PHF6 combined caused fully penetrant early-onset leukemia. Our data suggest that PHF6 is a hematopoietic tumor suppressor and is important for fine-tuning hematopoietic stem and progenitor cell homeostasis.
Peripheral serotonin causes dengue virus–induced thrombocytopenia through 5HT2 receptors
Authors: Masri Mohamad Fadhli Bin , Mantri Chinmay Kumar , Rathore Abhay P. S. , John Ashley L. St. 
Published: February 2019

Abstract
Dengue virus (DENV) is the most prevalent vector-borne viral pathogen, infecting millions of patients annually. Thrombocytopenia, a reduction in circulating platelet counts, is the most consistent sign of DENV-induced disease, independent of disease severity. However, the mechanisms leading to DENV-induced thrombocytopenia are unknown. Here, we show that thrombocytopenia is caused by serotonin derived from mast cells (MCs), which are immune cells that are present in the perivascular space and are a major peripheral source of serotonin. We show that during DENV infection, MCs release serotonin, which prompts platelet activation, aggregation, and enhanced phagocytosis, dependent on 5HT2A receptors. MC deficiency in mice or pharmacologic inhibition of MCs reversed thrombocytopenia. Furthermore, reconstitution of MC-deficient mice with wild-type MCs, but not MCs lacking serotonin synthesis resulting from deficiency in the enzyme tryptophan hydroxylase-1, restored the thrombocytopenic phenotype. Exogenous serotonin was also sufficient to overcome the effects of drugs that inhibit platelet activation in vitro and to restore thrombocytopenia in DENV-infected MC-deficient mice. Therapeutic targeting of 5HT2A receptors during DENV infection effectively prevented thrombocytopenia in mice. Similarly, serotonin derived from DENV-activated human MCs led to increased human platelet activation. Thus, MC-derived serotonin is a previously unidentified mechanism of DENV-induced thrombocytopenia and a potential therapeutic target.
Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations
Authors: Jutzi Jonas Samuel , Basu Titiksha , Pellmann Maximilian , Kaiser Sandra , Steinemann Doris , Sanders Mathijs A. , Hinai Adil S. A. , Zeilemaker Annelieke , Bojtine Kovacs Sarolta , Koellerer Christoph , Ostendorp Jenny , Aumann Konrad , Wang Wei , Raffoux Emmanuel , Cassinat Bruno , Bullinger Lars , Schlegelberger Brigitte , Valk Peter J. M. , Pahl Heike Luise 
Published: February 2019

Abstract
In acute myeloid leukemia (AML), acquired genetic aberrations carry prognostic implications and guide therapeutic decisions. Clinical algorithms have been improved by the incorporation of novel aberrations. Here, we report the presence and functional characterization of mutations in the transcription factor NFE2 in patients with AML and in a patient with myelosarcoma. We previously described NFE2 mutations in patients with myeloproliferative neoplasms and demonstrated that expression of mutant NFE2 in mice causes a myeloproliferative phenotype. Now, we show that, during follow-up, 34% of these mice transform to leukemia presenting with or without concomitant myelosarcomas, or develop isolated myelosarcomas. These myelosarcomas and leukemias acquired AML-specific alterations, including the murine equivalent of trisomy 8, loss of the AML commonly deleted region on chromosome 5q, and mutations in the tumor suppressor Trp53. Our data show that mutations in NFE2 predispose to the acquisition of secondary changes promoting the development of myelosarcoma and/or AML.
Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency
Authors: Castillo Michelle M. , Yang Qiuhui , Zhan Min , Pan Amy Y. , Lawlor Michael W. , Mast Alan E. , Sood Rashmi 
Published: February 2019

Abstract
Tissue factor pathway inhibitor (TFPI) is a serine protease with multiple anticoagulant activities. The Kunitz1 (K1) domain of TFPI binds the active site of factor VIIa and is required for inhibition of tissue factor (TF)/factor VIIa catalytic activity. Mice lacking TFPI K1 domain die in utero. TFPI is highly expressed on trophoblast cells of the placenta. We used genetic strategies to selectively ablate exon 4 encoding TFPI K1 domain in the embryo, while maintaining expression in trophoblast cells. This approach resulted in expected Mendelian frequency of TFPI K1 domain–deficient mice. Real-time polymerase chain reaction confirmed 95% to 99% genetic deletion and a similar reduction in transcript expression. Western blotting confirmed the presence of a truncated protein instead of full-length TFPI. Mice with severe TFPI K1 deficiency exhibited elevated thrombin-antithrombin (TAT) levels, frequent fibrin deposition in renal medulla, and increased susceptibility to TF-induced pulmonary embolism. They were fertile, and most lived normal life spans without any overt thrombotic events. Of 43 mice observed, 2 displayed extensive brain ischemia and infarction. We conclude that in contrast to complete absence of TFPI K1 domain, severe deficiency is compatible with in utero development, adult survival, and reproductive functions in mice. Inhibition of TFPI activity is being evaluated as a means of boosting thrombin generation in hemophilia patients. Our results show that in mice severe reduction of TFPI K1 activity is associated with a prothrombotic state without overt developmental outcomes. We note fibrin deposits in the kidney and rare cases of brain ischemia.
RETRACTED ARTICLE: Research on the perfection of the countermeasures of the judicial execution scheme in the administrative law system based on annealing algorithm
Authors: Qu Jiangze 
Published: February 2019

AbstractWith the continuous development of computer technology and the popularization and application of various types of intelligent algorithms, there are also applications in the current administrative judicial system in China. In order to be able to reasonably realize the fairness of criminal justice activities, the relevant deficiencies in the implementation of the supervision of criminal penalty enforcement are made up. In order to reasonably improve the execution plan, the legal authority of judicial administration is established. The implementation of the judicial enforcement program in the administrative law system is researched based on the annealing algorithm. The optimization of the annealing algorithm is used to optimize the execution of the program flow. The results show that the annealing algorithm can optimize this solution.
Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA
Authors: Rakhit Callum P. , Trigg Ricky M. , Le Quesne John , Kelly Michael , Shaw Jacqueline A. , Pritchard Catrin , Martins L. Miguel 
Published: February 2019

ABSTRACT
Lung cancer is the leading cause of cancer-related death. Two-thirds of cases are diagnosed at an advanced stage that is refractory to curative treatment. Therefore, strategies for the early detection of lung cancer are urgently sought. Total circulating free DNA (cfDNA) and tumour-derived circulating tumour DNA (ctDNA) are emerging as important biomarkers within a ‘liquid biopsy’ for monitoring human disease progression and response to therapy. Owing to the late clinical diagnosis of lung adenocarcinoma, the potential for cfDNA and ctDNA as early detection biomarkers remains unexplored. Here, using a Cre-regulated genetically engineered mouse model of lung adenocarcinoma development, driven by KrasG12D (the KrasLSL-G12D mouse), we serially tracked the release of cfDNA/ctDNA and compared this with tumour burden as determined by micro-computed tomography (CT). To monitor ctDNA, a droplet digital PCR assay was developed to permit discrimination of the KrasLox-G12D allele from the KrasLSL-G12D and KrasWT alleles. We show that micro-CT correlates with endpoint histology and is able to detect pre-malignant tumours with a combined volume larger than 7 mm3. Changes in cfDNA/ctDNA levels correlate with micro-CT measurements in longitudinal sampling and are able to monitor the emergence of lesions before the adenoma-adenocarcinoma transition. Potentially, this work has implications for the early detection of human lung adenocarcinoma using ctDNA/cfDNA profiling.
A video abstract for this article is available at https://youtu.be/Ku8xJJyGs3U.
This article has an associated First Person interview with the joint first authors of the paper.
Studies on gas exchange in the meadow spittlebug,Philaenus spumarius: the metabolic cost of feeding on, and living in, xylem sap
Authors: Beckett Kephra I. S. , Robertson Anne B. , Matthews Philip G. D. 
Published: February 2019

ABSTRACTSpittlebugs (superfamily Cercopoidea) live within a mass of frothy, spittle-like foam that is produced as a by-product of their xylem-feeding habits. The wet spittle represents a unique respiratory environment for an insect, potentially acting either as a reserve of trapped oxygen (O2) or as a significant barrier to O2 diffusion from the surrounding atmosphere. Feeding on xylem sap under tension is also assumed to be energetically expensive, potentially placing further constraints on their gas exchange. To understand the respiratory strategies used by spittlebugs, this study measured the PO2 within the spittle of the meadow spittlebug, Philaenus spumarius, as well as the non-feeding metabolic rate (RMR) and respiratory quotient (RQ) of both nymphs and adults. The metabolic rate of nymphs feeding on xylem was also measured. In separate experiments, the ability of a nymph to obtain O2 from bubbles while submerged in foam was determined using a glass microscope slide coated in an O2-sensitive fluorophore. We determined that P. spumarius breathes atmospheric O2 by extending the tip of its abdomen outside of its spittle, rather than respiring the O2 trapped in air bubbles within the foam. However, spittlebugs can temporarily use these air bubbles to breathe when forcibly submerged. V̇O2 and V̇CO2 did not differ statistically within life stages, giving a RQ of 0.92 for nymphs and 0.95 for adults. Feeding on xylem was found to increase the nymphs' V̇CO2 by only 20% above their RMR. From this cost of feeding, cibarial pump pressures were estimated to be between −0.05 and −0.26 MPa.
Biometric and genetic differences in kelabau (Osteochilus spp.) as revealed using cytochrome c oxidase subunit 1
Authors: Asiah Nur , Junianto Junianto , Yustiati Ayi , Sukendi Sukendi , Fahmi Melta Rini , Muchlisin Zainal A. , Kadapi Muhamad 
Published: February 2019

Background: Kelabau (Osteochilus spp.) is a freshwater fish commonly found in the rivers of Riau, Indonesia. Researchers believe that these are Osteochilus kelabau; however, accurate taxonomic determination of these fish in Riau waters has not been made. The purpose of this study was to facilitate the identification of the kelabau based on its morphology and genetics using biometric and cytochrome c oxidase subunit 1 (CO1) analyses, respectively. Methods: Fish samples were collected from the Siak, Kampar and Rokan rivers in Riau Province, Indonesia. The DNA of 90 fish was extracted from the caudal fins using a DNA extraction kit, after which it was amplified using primers Fish-F1 and Fish-R1. Sequencing was conducted by Applied Biosystems Macrogen Korea, and the DNA sequences were then edited and aligned using MEGA v. 7. All samples were BLAST-searched for identification using the National Center for Biotechnology Information and BOLD System. Phylogenetic trees were constructed, and similarity index was calculated using accession numbers AP011385.1 and KC631202.1 in GenBank. Results: Analysis of the consensus barcode sequence for 86 species revealed a high percentage of barcode matches (96%–97% in GenBank and 96.6%–96.76% in the BOLD System). The nucleotide distance between groups of kelabau from the different rivers based on the Kimura 2-parameter model gave the following results: 0.05% between groups from the Siak and Kampar rivers, 0.09% between those from the Siak and Rokan rivers and 0.05% between those from the Kampar and Rokan rivers. The nucleotide distance between the groups in the Siak (0.09%), Kampar (0.00%) and Rokan (0.10%) Rivers indicated that the kelabau in those rivers were related to each other. Conclusions: Based on the results of the research data using CO1 and biometric analyses, the kelabau were confirmed to be O. melanopleurus.
‘I'll never be the same’: the impact of an international elective
Authors: Carter Chris , Hunt Barbara Howard , Mukonka Priscar Sakala , Viveash Sue , Notter Joy , Toner Louise 
Published: February 2019

Background: many undergraduate student nurses have the opportunity to undertake an international elective—that is, a placement in another country. The benefits of undertaking an elective include developing cultural competence, understanding different healthcare systems and experiencing a different culture. Aim: the aim of the study was to evaluate the impact of a faculty-structured international travel elective to Zambia for undergraduate UK nursing students. Methods: a descriptive phenomenology approach was used to discover and explore the students' experiences of their elective. Findings: 6 students participated in semi-structured interviews. Themes that emerged included the importance of preparing for the elective, different nursing cultures, realities and patient safety concerns. Conclusion: this study found that students involved in an international elective to Zambia overall had a positive experience but did report some challenges; the findings contribute to the body of evidence relating to international electives.
Surveillance Colonoscopy for Ulcerative Colitis-Associated Colorectal Cancer Offers Better Overall Survival in Real-World Surgically Resected Cases
Authors: Hata Keisuke , Anzai Hiroyuki , Ikeuchi Hiroki , Futami Kitaro , Fukushima Kouhei , Sugita Akira , Uchino Motoi , Higashi Daijiro , Itabashi Michio , Watanabe Kazuhiro , Koganei Kazutaka , Araki Toshimitsu , Kimura Hideaki , Mizushima Tsunekazu , Ueda Takeshi , Ishihara Soichiro , Suzuki Yasuo ,   on behalf of the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan (RGIBD)
Published: February 2019

OBJECTIVES:
To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia.

METHODS:
Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (<8 years after UC onset) were identified. The distribution of CRC lesions was also assessed.

RESULTS:
Cancer stages were significantly more advanced in the non-SC group than in the SC group (P < 0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (<8 years) (P < 0.01; AUC: 0.85). The most common sites of CRC were the rectum (51%) and sigmoid colon (20%). Multiple CRC was identified in 16% of patients.

CONCLUSIONS:
Surveillance colonoscopy was effective and improved the OS in patients with UC. We recommend that patients with late-onset UC (>40 years) undergo SCs earlier because of the high incidence of CRC within 8 years of UC onset. Moreover, the rectum and sigmoid colon should be more thoroughly examined.
İşitme Engelliler Ortaokulunda Okuyan Öğrencilerin Din Kültürü ve Ahlak Bilgisine Dersine Yönelik Tutum ve Değerlendirmeleri: Amasya ve Samsun Örneği
Authors: GÜN Ayşegül 
Published: February 2019

Bu çalışma, işitme engelliler ortaokulunda okuyan öğrencilerin DKAB dersine yönelik tutumlarını tespit etmek amacıyla hazırlanmıştır. Bu amaçla, dokuz sorudan oluşan bir anket formu oluşturulmuş, Amasya ve Samsun illerinde bulunan iki işitme engelliler ortaokulunda uygulama yapılmıştır. Anket 63 öğrenciye uygulanmış ve verilen cevaplar bilgisayar ortamına aktarılarak yorumlanmıştır. Yorumlar yapılırken, çalışma esnasında yapılan gözlemlerden de yararlanılmıştır. Buna göre, işitme engelli öğrencilerin DKAB dersini çok sevdikleri ancak konuların ve ders kitabının anlaşılmasında bazı sorunlar yaşadıkları tespit edilmiştir. Çalışma kapsamında, bu sorunların oluşmasında rol oynayan etkenler üzerinde durulmuş ve işitme engelli öğrencilerin din eğitiminin önündeki engellerin kaldırılmasına yönelik önerilerde bulunulmuştur.
Arap Dilinde Edatların Yapı ve Fonksiyonu
Authors: HACIBEKİROĞLU Abdullah 
Published: February 2019

Bu makale edatların dil geleneğindeki kaynaklarını ve önceki bilginlerin onları inceleme yöntemlerini, bununla birlikte kendilerinden sonra gelen sözlüklerde hareke değişikliği oluşturup oluşturmama biçiminde ortaya çıkan dilbilgisel (nahvî) etkilerini, çoğu zaman üslup göstergesi olarak kabul edilen anlamsal işlevlerini açıklayan çifte yapılarını ve görevlerini ele almaktadır.
Contemporary commons: Sharing and managing common-pool resources in the 21st century
Authors: Šestáková Anna , Plichtová Jana 
Published: February 2019

Abstract
In her groundbreaking work, Elinor Ostrom suggested that communities are able to self-organize and develop rules which allow them to effectively manage common-pool resources while avoiding the “tragedy of the commons”, as proposed by Hardin. Based on empirical case studies of how forests, irrigation, grazing land and fisheries are organized all over the world, Ostrom suggested several principles that can serve as guidelines for managing common-pool resources. In the 21st century new initiatives have been based on sharing. There are various examples such as car and bike sharing in cities, internet platforms such as Wikipedia, community gardens and many others. There is a reason to believe that these efforts will continue to grow and become more popular as people realise the economic, social and ecological benefits. The aim of this paper is to analyse to what extent Ostrom’s findings are relevant to these new, often urbanised or digitalised forms of sharing. Can the famous design principles for which she won the Nobel prize be applied or do we need to search for a different set of principles that are more suitable for these new emerging forms of ‘the commons’? Our findings suggest that although Ostrom’s framework needs to be adapted before being applied to the reality of urban and digitalised environments, some of her findings remain relevant.
Maintaining borders: From border guards to diplomats
Authors: Espanol Alicia , Marsico Giuseppina , Tateo Luca 
Published: February 2019

Abstract
The article aims at integrating the cultural psychology perspective of into the multidisciplinary field of border studies. It analyses the border phenomenon as a co-genetic system. The authors investigate the psychological side of people who relate to the border out of different motives. Then, it expands some of the theoretical concepts current in border studies by introducing psychological dimensions such as intentionality and directionality. Finally, the framework is applied to two case-studies representing the northern and southern European Union frontiers: the case of Estonian officer Eston Kohver in the Setumaa region on the Estonian–Russian border; and the experiences of border guards in the re-bordering process on the Spanish– Moroccan border. It offers an innovative conceptual resource based on a triadic co-genetic epistemological approach, which allows us to overcome the binary oppositions still very present in the contemporary debates in borders studies.
Bio-Crude by Acidic Phenolation and Carbamation for the Preparation of Phenolic Thermosetting Resin and Its Application in Thermoresistant Laminates
Authors: Wang Huan , Wang Zhuo , Ren Penggang , Wang Mingcun 
Published: February 2019

Abstract
Fir sawdust was liquefied in phenol solvent under acidic catalyst at 135, 150 and 165 °C, respectively; after neutralization, bio-crude was obtained where contained oil-like liquid and tiny powder-like residue. The bio-crude was chemically modified with urea at high temperature (e. g. > 130 °C) to form carbamate so as to improve chemical reactivity of bio-crude in phenolic resin synthesis. The carbamate-containing bio-crude was condensed with paraformaldehyde into thermosetting phenolic resin. Finally, this biomass-derived phenolic resin matrixed silica fabric laminates were processed. The uncured and thermally cured bio-based resins were characterized by the techniques of Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectrum (FT-IR), rheology and Thermogravimetric Analysis (TGA), and the laminates’ structure and mechanical performances were studied using the methods of Scanning Electron Microscopy (SEM), three point bending mechanical test and Dynamic Mechanical Analysis (DMA). The results showed: (1) the chemical reactivity of bio-crude was highly improved by carbamation; (2) biomass-derived thermosetting phenolic resin was thermally curable at 150–250 °C (with two exothermic peaks at 185 °C and 220 °C); (3) the char yield was about 47 %, which was not in apparent relationship with sawdust liquefaction temperatures; (4) flexural strength of silica fabric laminates at room temperature was around 357 MPa (similar with that of conventional phenolic laminate); (5) glass transition temperature of silica fabric laminate was above 270 °C (much higher than Tg of conventional phenolic resin laminate, which is normally at 215 °C). The biomass-derived phenolic resin is expected to be widely used as cost-effective and environment-friendly thermosetting resin in the application of high-performance composites.