bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Flt3 ligand is biomarker of progenitor cell mass and prognosis in acute myeloid leukemia
Authors: Milne Paul , Wilhelm-Benartzi Charlotte , Grunwald Michael R. , Bigley Venetia , Publicover Amy , Pagan Sarah , Marr Helen , Jones Gail , Dickinson Anne , Grech Angela , Burnett Alan , Russell Nigel , Levis Mark , Knapper Steven , Collin Matthew 
Published: March 2019

AbstractFms-like tyrosine kinase 3 (Flt3) is a hematopoietic growth factor receptor expressed on lymphomyeloid progenitors and frequently, by AML blasts. Its ligand, Flt3L, has non-hematopoietic and lymphoid origins, is detectable during homeostasis and increases to high levels in states of hypoplasia due to genetic defects or treatment with cytoreductive agents. Measurement of Flt3L by ELISA reveals that Flt3+AML, is associated with depletion of Flt3L to undetectable levels. After induction chemotherapy, Flt3L is restored in patients entering CR, but remains depressed in those with refractory disease. Weekly sampling reveals marked differences in the kinetics of Flt3L response during the first 6 weeks of treatment, proportionate to the clearance of blasts and cellularity of the BM. In the UK NCRI AML17 trial, Flt3L was measured at day 26 in a subgroup of 135 patients with Flt3 mutation randomized to the tyrosine kinase inhibitor lestaurtinib. In these patients, attainment of CR was associated with higher Flt3L at day 26 (Mann-Whitney p < 0.0001). Day 26 Flt3L was also associated with survival: Flt3L ≤ 291pg/ml was associated with inferior event-free survival; and, Flt3L >1185pg/ml was associated with higher overall survival (p = 0.0119). Serial measurement of Flt3L in patients who had received a hematopoietic stem cell transplant for AML further illustrated the potential value of declining Flt3L to identify relapse. Together these observations suggest that measurement of Flt3L provides a non-invasive estimate of progenitor cell mass in most patients with AML, with the potential to inform clinical decisions.Graphical abstract
tailfindr: Alignment-free poly(A) length measurement for Oxford Nanopore RNA and DNA sequencing
Authors: Krause Maximilian , Niazi Adnan M. , Labun Kornel , Torres Cleuren Yamila N. , Müller Florian S. , Valen Eivind 
Published: March 2019

Polyadenylation at the 3’-end is a major regulator of messenger RNA and its length is known to affect nuclear export, stability and translation, among others. Only recently, strategies have emerged that allow for genome-wide poly(A) length assessment. These methods identify genes connected to poly(A) tail measurements indirectly by short-read alignment to genetic 3’-ends. Concurrently Oxford Nanopore Technologies (ONT) established full-length isoform RNA sequencing containing the entire poly(A) tail. However, assessing poly(A) length through basecalling has so far not been possible due the inability to resolve long homopolymeric stretches in ONT sequencing.Here we presenttailfindr, an R package to estimate poly(A) tail length on ONT long-read sequencing data.tailfindroperates on unaligned, basecalled data. It measures poly(A) tail length from both native RNA and DNA sequencing, which makes poly(A) tail studies by full-length cDNA approaches possible for the first time. We assesstailfindr’sperformance across different poly(A) lengths, demonstrating thattailfindris a versatile tool providing poly(A) tail estimates across a wide range of sequencing conditions.
Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes
Authors: McGlinchey Aidan , Sinioja Tim , Lamichhane Santosh , Sen Partho , Bodin Johanna , Siljander Heli , Dickens Alex M. , Geng Dawei , Carlsson Cecilia , Duberg Daniel , Ilonen Jorma , Virtanen Suvi M. , Dirven Hubert , Berntsen Hanne Friis , Zimmer Karin , Nygaard Unni C. , Orešič Matej , Knip Mikael , Hyötyläinen Tuulia 
Published: March 2019

AbstractIn the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.
Ontogeny and expression profiles of steroid hormone receptors in a mouse model of endometriosis
Authors: Mishra Anuradha , Galvankar Mosami , Singh Neha , Vaidya Shantashri , Chaudhari Uddhav , Modi Deepak 
Published: March 2019

ABSTRACTEndometriosis is a chronic incurable disorder of unknown etiology affecting a large proportion of women in reproductive age. In order to understand the pathogenesis and preclinical testing of drugs,animal models that recapitulate the key features of the disorder are highly desirous. Herein, we describe the ontogeny of the ectopic endometrial lesion in a mouse model where uterine tissue was ligated to the intestinal mesentery and the animals were followed up from day 5 to day 60 post-surgery. Out of 60 animals that underwent surgery, 58 developed endometriosis using this strategy. Most lesions were pale, fluid filled while red lesions were seen in ~10% of animals. Histologically, in most animals there was one large cystic gland with well differentiated epithelium, in 13% of animals there was mixed phenotype (well and poorly differentiated). There was extensive stromal compaction and increased number of macrophages in ectopic lesions. During the course of endometriosis, there was an increase in number of PCNA positive epithelial and stromal cells. The epithelial cells at all the time point were cytokeratin positive and the stroma was vimentin positive. However, at day 30 and 60, the stromal cells were also cytokeratin positive. The mRNA levels of estrogen receptorsEsr1andGper1were reduced while those ofEsr2were elevated as compared to normal endometrium, the levels of progesterone receptor (Pgr) were found to be downregulated in ectopic lesions as compared to control. However, these differences were not statistically significant due to high biological variability. Low abundance ofCyp19a1transcripts (aromatase gene) were only detected in the ectopic endometrium. Immunohistochemically, the expression of ERα and ERβ was significantly reduced only in stromal cells; the epithelial cell staining was maintained. GPER1 and PR immunoreactivity was significantly low in both epithelial and stromal cells. The immunostaining of all the steroid receptors was highly heterogeneous in the ectopic tissues with some areas of sections had stained intensely while others had negligible staining. We propose that temporal and spatial difference in the expression of steroid hormone receptors during the course of endometriosis development coupled with micro-heterogeneity may alter the effectiveness of steroid hormone analogues resulting in variable outcomes and often failure of therapy.
AluMine: alignment-free method for the discovery of polymorphic Alu element insertions
Authors: Puurand Tarmo , Kukuškina Viktoria , Pajuste Fanny-Dhelia , Remm Maido 
Published: March 2019

ABSTRACTBackgroundRecently, alignment-free sequence analysis methods have gained popularity in the field of personal genomics. These methods are based on counting frequencies of short k-mer sequences, thus allowing faster and more robust analysis compared to traditional alignment-based methods.ResultsWe have created a fast alignment-free method, AluMine, to analyze polymorphic insertions of Alu elements in the human genome. We tested the method on 2,241 individuals from the Estonian Genome Project and identified 28,962 potential polymorphic Alu element insertions. Each tested individual had on average 1,574 Alu element insertions that were different from those in the reference genome. In addition, we propose an alignment-free genotyping method that uses the frequency of insertion/deletion-specific 32-mer pairs to call the genotype directly from raw sequencing reads. Using this method, the concordance between the predicted and experimentally observed genotypes was 98.7%. The running time of the discovery pipeline is approximately 2 hours per individual. The genotyping of potential polymorphic insertions takes between 0.4 and 4 hours per individual, depending on the hardware configuration.ConclusionsAluMine provides tools that allow discovery of novel Alu element insertions and/or genotyping of known Alu element insertions from personal genomes within few hours.
Structural and mutational analysis of the ribosome-arresting human XBP1u
Authors: Shanmuganathan Vivekanandan , Schiller Nina , Magoulopoulou Anastasia , Cheng Jingdong , Braunger Katharina , Cymer Florian , Berninghausen Otto , Beatrix Birgitta , Kohno Kenji , von Heijne Gunnar , Beckmann Roland 
Published: March 2019

AbstractXBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 Å cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the upper part of the ribosomal exit tunnel and causes a subtle distortion of the peptidyl transferase center, explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 10 out of 21 mutagenized positions in the XBP1u AP are optimal with respect to translational arrest activity. Thus, XBP1u has evolved to induce an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel and thereby serving its central function in the UPR.
Study on the Health Communication Behavior of Chinese Doctors on Network Media——Based on the Empirical Investigation of 119 Chinese Doctors
Authors: Fangyuan Hu , Pu Wang 
Published: March 2019

AbstractIntroductionIn order to reduce the perceived risk of medical decision-making, Chinese patients tend to spend time and energy to understand relevant medical knowledge. After comparing online reviews and news reports of Chinese doctors, they carefully choose doctors. It is precisely because of the patient’s treatment habits that many doctors have spread health information through their own microblogs, WeChat public numbers, websites, videos and other means. Therefore, doctors’ speeches in cyberspace often play a dominant role in the development of health communication and guide the risk communication. This paper studies the influencing factors of Chinese doctors’ healthy communication behavior in online media. This has positive reference value for improving the health literacy of the whole people and the crisis management and guidance of public events.MethodsIn order to maximize the representativeness of the sample, the universality of the problems reflected in the survey data, and the adaptability of the purpose and method of the research questions, this paper adopts a multi-stage sampling method. In each region, a medical institution is selected according to a simple random sampling method in three types of hospitals: public hospitals, social hospitals, and primary medical institutions. A total of 10-11 medical institutions were selected in each region, and a total of 32 hospitals were selected from the three regions. According to the PPS sampling method, a corresponding number of working doctors are drawn in each hospital. Statistical analysis of the data was performed using SPSS 21.0 statistical software.AnalysisThe study found that doctors’ transmission of health-related content on online media is still at a lower level of involvement, and the frequency of transmission is significantly lower than the general level. There are also significant differences in the health transmission of doctors from different backgrounds on the Internet. In the context of control hospital background, continue to examine the impact of Media usage and occupational psychology on doctors’ dissemination of health-related content. The results show that the influence of Media usage on the health communication behavior of doctors on the Internet media, to a certain extent, verifies that the rise of online media plays a significant role in putting doctors into health science. This also shows that the media has fostered the doctor’s communication behavior. In addition, the higher the self-efficacy of doctors in the workplace, the more cautious they are about their words and deeds, the more they care about the impact of their speech on interpersonal communication.
Extensive adaptive immune response of AAVs and Cas proteins in non-human primates
Authors: Xiao Puhao , Bai Raoxian , Zhang Ting , Zhou Yin , Zhou Zhigang , Zhuo Yan , Gong Nannan , Liu Jie , Ren Shuaiwei , Wu Ruo , Shen Bin , Li Shangang , Niu Yuyu , Ji Weizhi , Chen Yongchang 
Published: March 2019

AbstractThe CRISPR-mediated Cas system is the most widely used tool in gene editing and gene therapy for its convenience and efficiency. Delivery of the CRISPR system by adeno-associated viruses (AAVs) is currently the most promising approach to gene therapy. However, pre-existing adaptive immune responses against CRISPR nuclease (PAIR-C) and AAVs has been found in human serum, indicating that immune response is a problem that cannot be ignored, especially for in vivo gene correction. Non-human primates (NHPs) share many genetic and physiological traits with human, and are considered as the bridge for translational medicine. However, whether NHPs have same PAIR-C status with human is still unknown. Here, macaques (rhesus and cynomolgus), including normal housed and CRISPR-SpCas9 or TALENs edited individuals, were used to detect PAIR-C which covered SaCas9, SpCas9, AsCas12a and LbCas12a. Dogs and mice were also detected to expand the range of species. In addition, pre-existing adaptive antibodies to AAV8 and AAV9 were performed against macaques of different ages. The results showed that adaptive immunity was pre-existing in the macaques regardless of Cas proteins and AAVs. These findings indicate that the pre-existing adaptive immune of AAV-delivered CRISPR construction and correction system should be concerned for in vivo experiments.
MgO nanoparticles coated with Polyethylene Glycol as carrier for 2-Methoxyestradiol anticancer drug
Authors: Alfaro Aline , León Andrea , Guajardo Eduardo , Reuquen Patricia , Torres Francisco , Mery Mario , Segura Rodrigo , Zapata Paula A. , Orihuela Pedro A. 
Published: March 2019

AbstractNovel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer poliethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy.
Emotional intelligence, emotional labor strategies and satisfaction of secondary teachers in Pakistan
Authors: Pervaiz Sonia , Ali Amjad , Asif Muhammad 
Published: March 2019

PurposeEmotional intelligence (EI) is crucial to determine the emotional labor (EL) strategies and satisfaction of teachers. The purpose of this paper is to investigate the relationships of EI with EL strategies, emotional exhaustion and teaching satisfaction (TS) of secondary teachers in private schools.Design/methodology/approachA self-administered questionnaire was used to collect data conveniently from 322 secondary teachers working in 22 private schools.FindingsResults indicate that teachers’ EI positively affect surface acting, expression of naturally felt emotions (ENFE) and TS. Surface acting and ENFE are positively related with TS. Deep acting and ENFE exhibit positive relations with emotional exhaustion of teachers. The study also confirms direct as well as indirect effects of EI on TS through surface acting and ENFE.Practical implicationsThis study recommends teachers to make a higher use of surface acting and ENFE because they produce the most TS and the least emotional exhaustion.Originality/valueThis is the first study that examines the mediating role of EL strategies for EI and TS.
Thinking about service encounters boosts talking about them
Authors: Söderlund Magnus , Mattsson Jan 
Published: March 2019

Purpose
This paper aims to examine the impact of thinking about an event as an antecedent to subsequent talk about this event with others (i.e. word-of-mouth). Thinking has been a neglected variable in word-of-mouth research, despite the fact that several conceptual arguments indicate that thinking is likely to enhance talking. Here, the thinking–talking association is examined in the context of service encounters.

Design/methodology/approach
Data were collected with a critical incident method, and the main variables were measured with questionnaire items.

Findings
Thinking about a service encounter – after it has been completed – had a positive influence on subsequent talk to others about the encounter. The association was mediated by the memorability of the service encounter and the extent to which what had happened had been subject to rehearsal with the purpose of telling others about it. In addition, with respect to antecedents of consumer thinking, the results indicate that service encounter incongruity had a special role in why the consumer thinks about encounters after they have been completed.

Originality/value
The findings should be seen in relation to the dominant position of customer satisfaction as an antecedent to word-of-mouth in the existing literature. The present results, however, indicate that satisfaction’s contribution to the variation in talking about the encounter was modest.
Disentangling serology to elucidate henipa‐ and filovirus transmission in Madagascar fruit bats
Authors: Brook Cara E. , Ranaivoson Hafaliana C. , Broder Christopher C. , Cunningham Andrew A. , Héraud Jean‐Michel , Peel Alison J. , Gibson Louise , Wood James L. N. , Metcalf C. Jessica , Dobson Andrew P. 
Published: March 2019

Abstract

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food.

We aimed to (a) document the extent of henipa‐ and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data.

To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa‐ and filovirus dynamics in three Madagascar fruit bat species.

We uncovered serological evidence of exposure to Hendra‐/Nipah‐related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar‐related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola‐related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population‐level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age‐structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult‐age bats.

Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population‐level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.
Non‐random loss of phylogenetically distinct rare species degrades phylogenetic diversity in semi‐natural grasslands
Authors: Uchida Kei , Hiraiwa Masayoshi K. , Cadotte Marc W. 
Published: March 2019

Abstract

Although biodiversity loss is a critically important topic, our understanding of how both land abandonment and land‐use intensification in semi‐natural grasslands alters the community diversity and assembly mechanisms is very limited. Large‐scale economic drivers of land‐use change might inadvertently result in the loss of vulnerable species and reduce ecosystem service provisioning.

In this study, we assessed non‐random community change by examining patterns of low‐abundance species loss, and community assembly in semi‐natural grasslands due to land abandonment and intensification in southwest Japan. We analysed relationships between evolutionary distinctiveness and abundance for each species. In addition, we used metrics of species and phylogenetic diversity and phylogenetic structure to assess patterns of non‐random biodiversity loss due to both abandoned and intensified land‐use.

We demonstrated that low‐abundance species were more evolutionarily distinct compared to high‐abundance (i.e. dominant) species. Furthermore, land‐use intensification resulted in further declines in low‐abundance species, whereas land abandonment resulted in declines in all species, regardless of their initial abundance.

We found that both forms of land‐use change (abandonment and intensification) resulted in non‐random patterns of community change, with traditional land‐use maintaining the highest biodiversity and land‐use change coinciding with decreased species and phylogenetic diversity measures. Intensified land‐use caused phylogenetic community structure to be more closely related than expected by chance, whereas the metrics of how distant species are from one another on average based on phylogenetic tree (i.e. mean pairwise phylogenetic distance) did not change from land abandonment.

Synthesis and applications. We show that the loss of phylogenetic diversity, and especially of low‐abundance species with high value of phylogenetic distinctiveness, resulted in non‐random community disassembly. Our results argue that in order to maintain biodiversity in these semi‐natural grasslands, traditional management practices should be encouraged over intensification and simple abandonment. Government agencies should adopt policies or provide incentives that encourage the maintenance of traditional practices in rural Japan, and elsewhere where the combination of land consolidation and abandonment are important conservation issues.