bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia
Authors: Gebru Melat T. , Atkinson Jennifer M. , Young Megan M. , Zhang Lijun , Tang Zhenyuan , Liu Zhenqiu , Lu Pinyi , Dower Christopher M. , Chen Longgui , Annageldiyev Charyguly , Sharma Arati , Imamura Kawasawa Yuka , Zhao Zhongming , Miller Barbara A. , Claxton David F. , Wang Hong-Gang 
Published: May 2020

Abstract
FLT3 is a frequently mutated gene that is highly associated with a poor prognosis in acute myeloid leukemia (AML). Despite initially responding to FLT3 inhibitors, most patients eventually relapse with drug resistance. The mechanism by which resistance arises and the initial response to drug treatment that promotes cell survival is unknown. Recent studies show that a transiently maintained subpopulation of drug-sensitive cells, so-called drug-tolerant "persisters" (DTPs), can survive cytotoxic drug exposure despite lacking resistance-conferring mutations. Using RNA sequencing and drug screening, we find that treatment of FLT3 internal tandem duplication AML cells with quizartinib, a selective FLT3 inhibitor, upregulates inflammatory genes in DTPs and thereby confers susceptibility to anti-inflammatory glucocorticoids (GCs). Mechanistically, the combination of FLT3 inhibitors and GCs enhances cell death of FLT3 mutant, but not wild-type, cells through GC-receptor–dependent upregulation of the proapoptotic protein BIM and proteasomal degradation of the antiapoptotic protein MCL-1. Moreover, the enhanced antileukemic activity by quizartinib and dexamethasone combination has been validated using primary AML patient samples and xenograft mouse models. Collectively, our study indicates that the combination of FLT3 inhibitors and GCs has the potential to eliminate DTPs and therefore prevent minimal residual disease, mutational drug resistance, and relapse in FLT3-mutant AML.
Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases
Authors: Kahn Justine M. , Brazauskas Ruta , Tecca Heather R. , Bo-Subait Stephanie , Buchbinder David , Battiwala Minoo , Flowers Mary E. D. , Savani Bipin N. , Phelan Rachel , Broglie Larisa , Abraham Allistair A. , Keating Amy K. , Daly Andrew , Wirk Baldeep , George Biju , Alter Blanche P. , Ustun Celalettin , Freytes Cesar O. , Beitinjaneh Amer M. , Duncan Christine , Copelan Edward , Hildebrandt Gerhard C. , Murthy Hemant S. , Lazarus Hillard M. , Auletta Jeffery J. , Myers Kasiani C. , Williams Kirsten M. , Page Kristin M. , Vrooman Lynda M. , Norkin Maxim , Byrne Michael , Diaz Miguel Angel , Kamani Naynesh , Bhatt Neel S. , Rezvani Andrew , Farhadfar Nosha , Mehta Parinda A. , Hematti Peiman , Shaw Peter J. , Kamble Rammurti T. , Schears Raquel , Olsson Richard F. , Hayashi Robert J. , Gale Robert Peter , Mayo Samantha J. , Chhabra Saurabh , Rotz Seth J. , Badawy Sherif M. , Ganguly Siddhartha , Pavletic Steven , Nishihori Taiga , Prestidge Tim , Agrawal Vaibhav , Hogan William J. , Inamoto Yoshihiro , Shaw Bronwen E. , Satwani Prakash 
Published: May 2020

Abstract
We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, &lt;1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was &lt;1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
Laboratory monitoring of hemophilia A treatments: new challenges
Authors: Lenting Peter J. 
Published: May 2020

Abstract
Monitoring factor VIII (FVIII) activity has traditionally been complicated by discrepancies between assays for the various sorts of FVIII molecules. The advent of novel nonfactor therapies (emicizumab, fitusiran, and anti-tissue factor pathway inhibitor antibodies) in hemophilia A poses a new level of difficulty on the laboratory monitoring of these patients. To use the correct assays and for a proper interpretation of their results, it is pertinent to understand the mode of action of these nonfactor agents. Furthermore, the biochemical consequences for the different types of activity assays (whether it be specific FVIII activity assays or global coagulation assays) should be taken into account as well. In this review, these aspects will be discussed. In addition, the use of various animal models to estimate FVIII-equivalence of the nonfactor therapies will be presented.
Study of VOCs release during drying of plantation-grown Pinus sylvestris and naturally grown Russian Pinus sylvestris
Authors: Shen Yulin , Zhang Xiaotao , He Qin , Wang Xia , Wang Zhe , Yang Junli , Chen Zhangjing , Yu Jianfang , Duo Huaqiong , Wang Ximing 
Published: May 2020

AbstractA study was carried out to investigate the release of volatile organic compounds (VOCs) during drying of plantation Pinus sylvestris grown in China and naturally grown Pinus sylvestris from Russia. Our purpose was to provide basic information that can help wood processing mills set their VOCs emission limits and control the exhaust gas within such limits. During conventional drying of the plantation Pinus sylvestris, a total of 22 chemical compounds were detected in the exhaust gas: 9 aldehydes including formaldehyde, 8 terpenes including α-pinene, and 3 additional compounds including alkane, and propylbenzene. The VOCs released during both conventional drying and high-temperature drying were the same. However, large amounts of benzene were detected during the high-temperature drying process. During conventional drying of the Russian Pinus sylvestris material, a total of 17 chemical compounds were detected: 7 aldehydes including formaldehyde, 6 terpenes including α-pinene, and 2 additional compounds. The VOCs released during conventional drying and high-temperature drying were the same. However, large amounts of camphene were detected during high-temperature drying. For plantation Pinus sylvestris, the release of VOCs primarily took place at the later stage of conventional drying, and at the earlier stage of high-temperature drying. For Russian Pinus sylvestris, the amount and the release rate of VOCs during conventional drying were extremely low, and the VOCs during high-temperature drying were primarily released at the later stage. The total amount of VOCs released during drying was much higher from the plantation Pinus sylvestris than from Russian Pinus sylvestris material.
Evolution of Fusarium tricinctum and Fusarium avenaceum mitochondrial genomes is driven by mobility of introns and of a new type of palindromic microsatellite repeats
Authors: Ponts Nadia , Gautier Charlotte , Gouzy Jérôme , Pinson-Gadais Laetitia , Foulongne-Oriol Marie , Ducos Christine , Richard-Forget Florence , Savoie Jean-Michel , Zhao Chen , Barroso Gérard 
Published: May 2020

Abstract
Background
Increased contamination of European and Asian wheat and barley crops with “emerging” mycotoxins such as enniatins or beauvericin, produced by Fusarium avenaceum and Fusarium tricinctum, suggest that these phylogenetically close species could be involved in future food-safety crises.

Results
The mitochondrial genomes of F. tricinctum strain INRA104 and F. avenaceum strain FaLH27 have been annotated. A comparative analysis was carried out then extended to a set of 25 wild strains. Results show that they constitute two distinct species, easily distinguished by their mitochondrial sequences. The mitochondrial genetic variability is mainly located within the intergenic regions. Marks of variations show they have evolved (i) by Single Nucleotide Polymorphisms (SNPs), (ii) by length variations mediated by insertion/deletion sequences (Indels), and (iii) by length mutations generated by DNA sliding events occurring in mononucleotide (A)n or (T)n microsatellite type sequences arranged in a peculiar palindromic organization. The optionality of these palindromes between both species argues for their mobility. The presence of Indels and SNPs in palindrome neighbouring regions suggests their involvement in these observed variations. Moreover, the intraspecific and interspecific variations in the presence/absence of group I introns suggest a high mobility, resulting from several events of gain and loss during short evolution periods. Phylogenetic analyses of intron orthologous sequences suggest that most introns could have originated from lateral transfers from phylogenetically close or distant species belonging to various Ascomycota genera and even to the Basidiomycota fungal division.

Conclusions
Mitochondrial genome evolution between F. tricinctum and F. avenaceum is mostly driven by two types of mobile genetic elements, implicated in genome polymorphism. The first one is represented by group I introns. Indeed, both genomes harbour optional (inter- or intra-specifically) group I introns, all carrying putatively functional hegs, arguing for a high mobility of these introns during short evolution periods. The gain events were shown to involve, for most of them, lateral transfers between phylogenetically distant species. This study has also revealed a new type of mobile genetic element constituted by a palindromic arrangement of (A) n and (T) n microsatellite sequences whose presence was related to occurrence of SNPs and Indels in the neighbouring regions.
The impact of mental fatigue on brain activity: a comparative study both in resting state and task state using EEG
Authors: Li Gang , Huang Shan , Xu Wanxiu , Jiao Weidong , Jiang Yonghua , Gao Zhao , Zhang Jianhua 
Published: May 2020

Abstract
Background
Mental fatigue is usually caused by long-term cognitive activities, mainly manifested as drowsiness, difficulty in concentrating, decreased alertness, disordered thinking, slow reaction, lethargy, reduced work efficiency, error-prone and so on. Mental fatigue has become a widespread sub-health condition, and has a serious impact on the cognitive function of the brain. However, seldom studies investigate the differences of mental fatigue on electrophysiological activity both in resting state and task state at the same time. Here, twenty healthy male participants were recruited to do a consecutive mental arithmetic tasks for mental fatigue induction, and electroencephalogram (EEG) data were collected before and after each tasks. The power and relative power of five EEG rhythms both in resting state and task state were analyzed statistically.

Results
The results of brain topographies and statistical analysis indicated that mental arithmetic task can successfully induce mental fatigue in the enrolled subjects. The relative power index was more sensitive than the power index in response to mental fatigue, and the relative power for assessing mental fatigue was better in resting state than in task state. Furthermore, we found that it is of great physiological significance to divide alpha frequency band into alpha1 band and alpha2 band in fatigue related studies, and at the same time improve the statistical differences of sub-bands.

Conclusions
Our current results suggested that the brain activity in mental fatigue state has great differences in resting state and task state, and it is imperative to select the appropriate state in EEG data acquisition and divide alpha band into alpha1 and alpha2 bands in mental fatigue related researches.
Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke
Authors: Zhang Ke-Ying , Rui Gang , Zhang Jun-Ping , Guo Ling , An Guang-Zhou , Lin Jia-Jin , He Wei , Ding Gui-Rong 
Published: May 2020

Abstract
Background
Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO).

Results
We established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague–Dawley rats, and then they were randomly divided into four groups (MCAO + tDCS, MCAO + sham tDCS (Sham), Control + tDCS and Control + Sham group). In this study, the severity degree of neurological deficit, the morphology of brain damage, the apoptosis, the level of neuron-specific enolase and inflammatory factors, the activation of glial cells was detected. The results showed that cathodal tDCS significantly improved the level of neurological deficit and the brain morphology, reduced the brain damage area and apoptotic index, and increased the number of Nissl body in MCAO rats, compared with MCAO + Sham group. Meanwhile, the high level of NSE, inflammatory factors, Caspase 3 and Bax/Bcl2 ratio in MCAO rats was reduced by cathodal tDCS. Additionally, cathodal tDCS inhibited the activation of astrocyte and microglia induced by MCAO. No difference was found in two Control groups.

Conclusion
Our results suggested that cathodal tDCS could accelerate the recovery of neurologic deficit and brain damage caused by MCAO. The inhibition of neuroinflammation and apoptosis resulted from cathodal tDCS may be involved in the neuroprotective process.
Assessment of violet-blue color formation in Phalaenopsis orchids
Authors: Liang Che-Yu , Rengasamy Krishna Preethi , Huang Li-Min , Hsu Chia-Chi , Jeng Mei-Fen , Chen Wen-Huei , Chen Hong-Hwa 
Published: May 2020

Abstract
Background
Phalaenopsis represents an important cash crop worldwide. Abundant flower colors observed in Phalaenopsis orchids range from red-purple, purple, purple-violet, violet, and violet-blue. However, violet-blue orchids are less bred than are those of other colors. Anthocyanin, vacuolar pH and metal ions are three major factors influencing flower color. This study aimed to identify the factors causing the violet-blue color in Phalaenopsis flowers and to analyze whether delphinidin accumulation and blue pigmentation formation can be achieved by transient overexpression of heterologous F3’5’H in Phalaenopsis.

Results
Cyanidin-based anthocyanin was highly accumulated in Phalaenopsis flowers with red-purple, purple, purple-violet, and violet to violet-blue color, but no true-blue color and no delphinidin was detected. Concomitantly, the expression of PeF3’H (Phalaenopsis equestrsis) was high, but that of PhF3’5’H (Phalaenopsis hybrid) was low or absent in various-colored Phalaenopsis flowers. Transient overexpression of DgF3’5’H (Delphinium grandiflorum) and PeMYB2 in a white Phalaenopsis cultivar resulted a 53.6% delphinidin accumulation and a novel blue color formation. In contrast, transient overexpression of both PhF3’5’H and PeMYB2 did not lead to delphinidin accumulation. Sequence analysis showed that the substrate recognition site 6 (SRS6) of PhF3’5’H was consistently different from DgF3’5’Hs at positions 5, 8 and 10. Prediction of molecular docking of the substrates showed a contrary binding direction of aromatic rings (B-ring) with the SRS6 domain of DgF3’5’H and PhF3’5’H. In addition, the pH values of violet-blue and purple Phalaenopsis flowers ranged from 5.33 to 5.54 and 4.77 to 5.04, respectively. Furthermore, the molar ratio of metal ions (including Al3+, Ca2+ and Fe3+) to anthocyanin in violet-blue color Phalaenopsis was 190-, 49-, and 51-fold higher, respectively, than those in purple-color Phalaenopsis.

Conclusion
Cyanidin-based anthocyanin was detected in violet-blue color Phalaenopsis and was concomitant with a high pH value and high molar ratio of Al3+, Ca2+ and Fe3+ to anthocyanin content. Enhanced expression of delphinidin is needed to produce true-blue Phalaenopsis.
Tree peony variegated flowers show a small insertion in the F3’H gene of the acyanic flower parts
Authors: Zhang Yanzhao , Cheng Yanwei , Xu Shuzhen , Ma Huiping , Han Jianming , Zhang Yan 
Published: May 2020

Abstract
Background
The tree peony (Paeonia suffruticosa Andr.) cultivar ‘Er Qiao’ is appreciated for its unstable variegated flower coloration, with cyanic and acyanic flowers appearing on different branches of the same plant and occasionally in a single flower or petal. However, the variegation mechanism is still unclear.

Results
In this study, we found significantly higher contents and more diverse sets of anthocyanins in the cyanic petals than in the acyanic petals. Comparative transcriptome analysis between the two flower types revealed 477 differentially expressed genes (DEGs). Quantitative real-time PCR results verified that the transcript levels of the flavonol synthase (FLS) gene were significantly increased in the acyanic petals. Furthermore, we found that a GCGGCG insertion at 246 bp in the flavonoid 3′-hydroxylase (F3’H) gene-coding region constitutes a duplication of the 241–245 bp section and was consistently found only in acyanic flowers. Sequence alignment of the F3’H gene from different plant species indicated that only the acyanic petals of ‘Er Qiao’ contained the GCGGCG insertion. The transformation of Arabidopsis tt7–1 lines demonstrated that the ectopic expression of F3’H-cyanic, but not F3’H-acyanic, could complement the colors in the hypocotyl and seed coat.

Conclusion
In summary, we found that an indel in F3’H and the upregulation of FLS drastically reduced the anthocyanin content in acyanic petals. Our results provide molecular candidates for a better understanding of the variegation mechanisms in tree peony.
Characterization of genetic determinants of the resistance to phylloxera, Daktulosphaira vitifoliae, and the dagger nematode Xiphinema index from muscadine background
Authors: Rubio Bernadette , Lalanne-Tisné Guillaume , Voisin Roger , Tandonnet Jean-Pascal , Portier Ulysse , Van Ghelder Cyril , Lafargue Maria , Petit Jean-Pierre , Donnart Martine , Joubard Benjamin , Bert Pierre-François , Papura Daciana , Le Cunff Loïc , Ollat Nathalie , Esmenjaud Daniel 
Published: May 2020

AbstractBackgroundMuscadine (Muscadinia rotundifolia) is known as a resistance source to many pests and diseases in grapevine. The genetics of its resistance to two major grapevine pests, the phylloxeraD. vitifoliaeand the dagger nematodeX. index, vector of theGrapevine fanleaf virus(GFLV), was investigated in a backcross progeny between the F1 resistant hybrid material VRH8771 (Vitis-Muscadinia) derived from the muscadine R source ‘NC184–4’ andV. viniferacv. ‘Cabernet-Sauvignon’ (CS).ResultsIn this pseudo-testcross, parental maps were constructed using simple-sequence repeats markers and single nucleotide polymorphism markers from a GBS approach. For the VRH8771 map, 2271 SNP and 135 SSR markers were assembled, resulting in 19 linkage groups (LG) and an average distance between markers of 0.98 cM. Phylloxera resistance was assessed by monitoring root nodosity number in anin plantaexperiment and larval development in a root in vitro assay. Nematode resistance was studied using 10–12 month long tests for the selection of durable resistance and rating criteria based on nematode reproduction factor and gall index. A major QTL for phylloxera larval development, explaining more than 70% of the total variance and co-localizing with a QTL for nodosity number, was identified on LG 7 and designatedRDV6. Additional QTLs were detected on LG 3 (RDV7) and LG 10 (RDV8), depending on thein plantaor in vitro experiments, suggesting that various loci may influence or modulate nodosity formation and larval development. Using a Bulked Segregant Analysis approach and a proportion test, markers clustered in three regions on LG 9, LG 10 and LG 18 were shown to be associated to the nematode resistant phenotype. QTL analysis confirmed the results and QTLs were thus designated respectivelyXiR2, XiR3 and XiR4, although a LOD-score below the significant threshold value was obtained for the QTL on LG 18.ConclusionsBased on a high-resolution linkage map and a segregating grapevine backcross progeny, the first QTLs for resistance toD. vitifoliaeand toX. indexwere identified from a muscadine source. All together these results open the way to the development of marker-assisted selection in grapevine rootstock breeding programs based on muscadine derived resistance to phylloxera and toX. indexin order to delay GFLV transmission.
“Analysis of readmissions to the emergency department among patients presenting with abdominal pain”
Authors: Kacprzyk Artur , Stefura Tomasz , Chłopaś Katarzyna , Trzeciak Kaja , Załustowicz Aleksandra , Rubinkiewicz Mateusz , Pędziwiatr Michał , Rembiasz Kazimierz , Major Piotr 
Published: May 2020

Abstract
Background
Abdominal pain is one of the most common complaints among patients admitted to the Emergency Department (ED). Diagnosis and management of abdominal pain may be a challenge and there are patients who require admission to the ED more than once in a short period of time. Our purpose was to assess the incidence of readmissions among patients treated in the ED due to abdominal pain and to investigate the impact of readmission on the further course of treatment.

Methods
We conducted a prospective observational study, which included patients admitted to the ED in one academic, teaching hospital presenting with non-traumatic abdominal pain in a three-month period. Analyzed factors included demographic data, details related to first and subsequent visits in the ED and the course of hospitalization.

Results
Overall, 928 patients were included to the study and 101 (10.88%) patients were admitted to the ED more than once during three-month period. Patients visiting ED repeatedly were older (p = 0.03) and more likely to be hospitalized (p < 0.01) compared to single-visit patients. Patients during their subsequent visits spent more time in the ED (p = 0.01), had greater chance to repeat their appointment (p = 0.04), be admitted to the hospital (p < 0.01) and were more likely diagnosed with cholelithiasis (p = 0.03) compared to patients on their initial visit. If admitted to the surgical department they were also more often qualified for surgical procedure than patients on their first visit (p < 0.01). In a group of patients admitted to the surgical department there were no significant differences in rates of conversion, postoperative complications and mortality between subgroups.

Conclusions
Readmissions among patients presenting with abdominal pain are a common phenomenon with prevalence of 10.88%. They are most commonly associated with cholelithiasis and occur more frequently among older patients, which suggests, that elderly require more attention during ED managements.