bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of SF3B1/DNMT3A Comutations With DNMT3A or SF3B1 Mutation Alone in Myelodysplastic Syndrome and Clonal Cytopenia of Undetermined Significance
Authors: Song Jinming , Hussaini Mohammad , Qin Dahui , Zhang Xiaohui , Shao Haipeng , Zhang Ling , Gajzer David , Basra Pukhraz , Moscinski Lynn , Zhang Hailing 
Published: January 2020

Abstract

Objectives
To compare the clinical significance of SF3B1/DNMT3A Comutations with SF3B1 or DNMT3A mutation alone in myelodysplastic syndrome (MDS) and clonal cytopenia of undetermined significance (CCUS).

Methods
We identified and compared 31 patients with only DNMT3A mutation, 48 patients with only SF3B1 mutation, and 16 patients with only SF3B1/DNMT3A comutations.

Results
SF3B1/DNMT3A comutations were found to be more common in MDS, whereas DNMT3A mutation alone was more common in CCUS. The patients with SF3B1/DNMT3A comutations were less likely to have poor cytogenetics than patients with DNMT3A mutation alone. Patients with SF3B1/DNMT3A comutations showed significantly longer median survival time and better overall survival than patients with DNMT3A mutation alone.

Conclusions
Patients with SF3B1/DNMT3A comutations appear to have better clinical outcomes than patients with isolated DNMT3A mutation. These findings suggest that the favorable prognosis of SF3B1 mutation in is not abrogated by the concurrent presence of a DNMT3A mutation.
Therapeutic Phlebotomy for Testosterone-Induced Polycythemia
Authors: Van Buren Nancy L , Hove Anita J , French Tracy A , Gorlin Jed B 
Published: January 2020

Abstract

Objectives
To evaluate therapeutic phlebotomy (TP) requests for testosterone replacement therapy (TRT) and to highlight the impact to a blood center (BC) or service that provides TP for individuals on TRT.

Methods
Review of TP requests for individuals on TRT at our BC over a 3-year period from 2014 through 2016, as well as the total number of TP collections.

Results
Total TPs during 2014, 2015, and 2016 were 475, 500, and 569, respectively. Annual TP collections for patients on TRT were 193, 212, and 239, respectively. TRT patients with TP orders increased 71.4% during this period. After discontinuation of TP services for TRT at our BC, 32% continued to donate as volunteer blood donors at our BC.

Conclusions
Our BC observed increased TP requests for patients on TRT from 2014 through 2016. Our findings suggest that individuals on TRT may be presenting to BCs as volunteer blood donors to avoid charges for TP.
Evaluation of burnout among hospital and health-system pharmacists in North Carolina
Authors: Kang Kai , Absher Randy , Granko Robert P 
Published: January 2020

AbstractPurposeTo assess the current state of burnout among pharmacists who work in hospital and health-system settings in North Carolina.MethodsThe Maslach Burnout Inventory-Human Services Survey for Medical Professionals was used to assess burnout in this study. This survey measures 3 subscales of burnout: emotional exhaustion, depersonalization, and personal accomplishment. In addition to the Maslach Burnout Inventory, the survey asked questions addressing various modifiable and nonmodifiable demographic factors. To distribute the survey, an email listserv of all pharmacists licensed in the state was obtained from the North Carolina Board of Pharmacy. The survey was distributed through email in June 2018. A follow-up email encouraging participation in the survey was sent 2 weeks later. The survey was open for a total of 4 weeks.ResultsThe survey was delivered to 2,524 pharmacists; 380 responses were received (15.1% response rate). Of the 380 individuals who responded, 357 completed the entire survey (93.9% completion rate), and 198 pharmacists (55.5%) were at risk for burnout. Following multivariate logistic regression, 3 factors were significantly associated with increased risk of burnout: female gender, working in a primarily distribution role, and longer hours worked per week. Two factors were significantly associated with decreased risk of burnout: being aware of burnout resources and working 4 to 6 months with learners.ConclusionThe results of this statewide survey revealed that more than half of hospital and health system–based pharmacists are at risk for burnout.
Transcompp: understanding phenotypic plasticity by estimating Markov transition rates for cell state transitions
Authors: Jagannathan N Suhas , Ihsan Mario O , Kin Xiao Xuan , Welsch Roy E , Clément Marie-Véronique , Tucker-Kellogg Lisa 
Published: January 2020

Abstract

Motivation
Gradual population-level changes in tissues can be driven by stochastic plasticity, meaning rare stochastic transitions of single-cell phenotype. Quantifying the rates of these stochastic transitions requires time-intensive experiments, and analysis is generally confounded by simultaneous bidirectional transitions and asymmetric proliferation kinetics. To quantify cellular plasticity, we developed Transcompp (Transition Rate ANalysis of Single Cells to Observe and Measure Phenotypic Plasticity), a Markov modeling algorithm that uses optimization and resampling to compute best-fit rates and statistical intervals for stochastic cell-state transitions.

Results
We applied Transcompp to time-series datasets in which purified subpopulations of stem-like or non-stem cancer cells were exposed to various cell culture environments, and allowed to re-equilibrate spontaneously over time. Results revealed that commonly used cell culture reagents hydrocortisone and cholera toxin shifted the cell population equilibrium toward stem-like or non-stem states, respectively, in the basal-like breast cancer cell line MCF10CA1a. In addition, applying Transcompp to patient-derived cells showed that transition rates computed from short-term experiments could predict long-term trajectories and equilibrium convergence of the cultured cell population.

Availability and implementation
Freely available for download at http://github.com/nsuhasj/Transcompp.

Supplementary information
Supplementary data are available at Bioinformatics online.
Transfer index, NetUniFrac and some useful shortest path-based distances for community analysis in sequence similarity networks
Authors: Xing Henry , Kembel Steven W , Makarenkov Vladimir 
Published: January 2020

Abstract

Motivation
Phylogenetic trees and the methods for their analysis have played a key role in many evolutionary, ecological and bioinformatics studies. Alternatively, phylogenetic networks have been widely used to analyze and represent complex reticulate evolutionary processes which cannot be adequately studied using traditional phylogenetic methods. These processes include, among others, hybridization, horizontal gene transfer, and genetic recombination. Nowadays, sequence similarity and genome similarity networks have become an efficient tool for community analysis of large molecular datasets in comparative studies. These networks can be used for tackling a variety of complex evolutionary problems such as the identification of horizontal gene transfer events, the recovery of mosaic genes and genomes, and the study of holobionts.

Results
The shortest path in a phylogenetic tree is used to estimate evolutionary distances between species. We show how the shortest path concept can be extended to sequence similarity networks by defining five new distances, NetUniFrac, Spp, Spep, Spelp and Spinp, and the Transfer index, between species communities present in the network. These new distances can be seen as network analogs of the traditional UniFrac distance used to assess dissimilarity between species communities in a phylogenetic tree, whereas the Transfer index is intended for estimating the rate and direction of gene transfers, or species dispersal, between different phylogenetic, or ecological, species communities. Moreover, NetUniFrac and the Transfer index can be computed in linear time with respect to the number of edges in the network. We show how these new measures can be used to analyze microbiota and antibiotic resistance gene similarity networks.

Availability and implementation
Our NetFrac program, implemented in R and C, along with its source code, is freely available on Github at the following URL address: https://github.com/XPHenry/Netfrac.

Supplementary information
Supplementary data are available at Bioinformatics online.
Genome-wide analysis of alternative splicing differences between oocyte and zygote†
Authors: Cheng Rui , Zheng Xiaoman , Wang Yingmei , Wang Mengyun , Zhou Chuan , Liu Jun , Zhang Yong , Quan Fusheng , Liu Xu 
Published: January 2020

Abstract
Alternative splicing (AS) of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, significantly expanding the information content and regulatory possibilities of higher eukaryotic genomes. During mammalian development, AS drives certain decisive changes in different physiological processes. As development progresses, the maternal-to-zygotic transition (MZT) will trigger two processes: elimination of a subset of maternal mRNA and transcription of the zygote genome begins. Recent high-throughput technological advancements have facilitated genome-wide AS, whereas its analysis in mouse oocyte transition to the zygote stage has not been reported. We present a high-resolution global analysis of AS transitions and discovered extensive AS transitions between mouse oocyte and zygote. The difference of AS patterns was further confirmed using reverse transcription-polymerase chain reaction analysis. Many genes with specific AS events in mouse oocytes are differentially expressed between oocyte and zygote, but only a few genes with specific AS events in zygote are differentially expressed between oocyte and zygote. We provide a landscape of AS events in mouse oocyte and zygote. Our results advance the understanding of AS transitions during mouse fertilization and its potential functions for MZT and further development.
On The (k,t)-Metric Dimension Of Graphs
Authors: Estrada-Moreno A , Yero I G , Rodríguez-Velázquez J A 
Published: January 2020

Abstract
Let $(X,d)$ be a metric space. A set $S\subseteq X$ is said to be a $k$-metric generator for $X$ if and only if for any pair of different points $u,v\in X$, there exist at least $k$ points $w_1,w_2, \ldots w_k\in S$ such that $d(u,w_i)\ne d(v,w_i),\; \textrm{for all}\; i\in \{1, \ldots k\}.$ Let $\mathcal{R}_k(X)$ be the set of metric generators for $X$. The $k$-metric dimension $\dim _k(X)$ of $(X,d)$ is defined as $$\begin{equation*}\dim_k(X)=\inf\{|S|:\, S\in \mathcal{R}_k(X)\}.\end{equation*}$$Here, we discuss the $k$-metric dimension of $(V,d_t)$, where $V$ is the set of vertices of a simple graph $G$ and the metric $d_t:V\times V\rightarrow \mathbb{N}\cup \{0\}$ is defined by $d_t(x,y)=\min \{d(x,y),t\}$ from the geodesic distance $d$ in $G$ and a positive integer $t$. The case $t\ge D(G)$, where $D(G)$ denotes the diameter of $G$, corresponds to the original theory of $k$-metric dimension, and the case $t=2$ corresponds to the theory of $k$-adjacency dimension. Furthermore, this approach allows us to extend the theory of $k$-metric dimension to the general case of non-necessarily connected graphs. Finally, we analyse the computational complexity of determining the $k$-metric dimension of $(V,d_t)$ for the metric $d_t$.
Role of atrial arrhythmia and ventricular response in atrial fibrillation induced atrial remodelling
Authors: Guichard Jean-Baptiste , Xiong Feng , Qi Xiao-Yan , L’Heureux Nathalie , Hiram Roddy , Xiao Jiening , Naud Patrice , Tardif Jean-Claude , Da Costa Antoine , Nattel Stanley 
Published: January 2020

Abstract

Aims
No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial vs. associated ventricular arrhythmia to remodelling. This study assessed the roles of atrial arrhythmia vs. high ventricular rate in AF-associated remodelling.

Methods and results
Four primary dog-groups (12/group) were subjected to 3-week pacing: 600-b.p.m. atrial tachypacing maintaining AF [AF w/o- atrioventricular block (AVB)]; atrial tachypacing with atrioventricular-node ablation (AF+AVB) and ventricular-demand pacing (80 b.p.m.); 160-b.p.m. ventricular-tachypacing (V160) reproducing the response rate during AF; and sinus rhythm with AVB/ventricular-pacing at 80-b.p.m. (control group). At terminal study, left-atrial (LA) effective refractory period (ERP) was reduced equally in both AF groups (w/o-AVB and AF+AVB). AF-inducibility was increased strongly in AF groups (w/o-AVB and AF+AVB) and modestly in V160. AF duration was significantly increased in AF w/o-AVB but not in AF+AVB or V160. Conduction velocity was decreased in AF w/o-AVB, to a greater extent than in AF+AVB and V160. Atrial fibrous-tissue content was increased in AF w/o-AVB, AF+AVB and V160, with collagen-gene up-regulation only in AF w/o-AVB. Connexin43 gene expression was reduced only in AF w/o-AVB. An additional group of 240-b.p.m. ventricular tachypacing dogs (VTP240; to induce heart failure) was studied: vs. other tachypaced groups, VTP240 caused greater fibrosis, but no change in LA-ERP or AF-inducibility. VTP240 also increased AF duration, strongly decreased left ventricular ejection fraction, and was the only group with LA natriuretic-peptide activation.

Conclusion
The atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodelling; both contribute to the arrhythmogenic substrate, providing new insights into AF-related remodelling and novel considerations for ventricular rate-control.
OP03 Reduced need for surgery and medical therapy after early ileocaecal resection for Crohn’s disease: Long-term follow-up of the LIR!C trial
Authors: Stevens T , Haasnoot L , D’Haens G , Buskens C , de Groof E J , Eshuis E , Gardenbroef T , Mol B , Stokkers P , Bemelman W , Ponsioen C 
Published: January 2020

Abstract

Background
The LIR!C trial showed that laparoscopic ileocaecal resection is at least as good as anti-TNF in terms of quality of life and is cost-saving. Current aims were to compare the long-term outcome of both interventions and to identify factors associated with the failure of the initial therapeutic strategy.

Methods
Long-term data were retrospectively collected for patients who participated in the LIR!C trial, a multicentre, randomised controlled trial that compared a laparoscopic ileocaecal resection with infliximab for adult patients with non-stricturing and immunomodulator refractory ileocaecal Crohn’s disease. Outcomes of interest needed for (re-)surgery or anti-TNF, duration of treatment effect as well as the identification of factors associated with sustained treatment effect. The treatment effect was defined as the time without the need for additional Crohn-related treatment. Potential factors were defined a priori and analysed by multivariable Cox regression analysis.

Results
Median follow-up time was 63.5 [IQR 39 – 94.5] months. In the resection group, 18 (26.1%) patients started anti-TNF treatment while none of the patients required a second resection (Figure 1). Twenty-nine (42%) patients did not require additional Crohn-related treatment. In contrast, in the infliximab group, 31 (47.7%) patients underwent a Crohn-related resection. Duration of treatment effect was similar with a median (95% CI) time without additional treatment of 33 (15.1–50.9) and 34 (0–69.3) months in the resection and infliximab group respectively (log-rank p = 0.521). In both groups, prophylactic immunomodulators decreased the risk of additional treatment (HR 0.34 95% CI (0.16–0.69) and HR 0.49 95% CI (0.26–0.93), respectively).

Conclusion
This long-term follow-up study of the LIR!C trial showed that after a median follow-up of 5 years the majority of patients who underwent resection were free of anti-TNF treatment, none required a second resection and almost half were free of any additional medical treatment for disease flares. Conversely, almost half of the patients in the infliximab group moved on to a Crohn-related resection. These data support early ileocaecal resection in Crohn’s disease patients not responding to conventional treatment.
OP07 The epidemiology of inflammatory bowel diseases among immigrants to Denmark: A population-based cohort study
Authors: Agrawal M , Shrestha S , Corn G , Nielsen N M , Frisch M , Colombel J F , Jess T 
Published: January 2020

Abstract

Background
The incidence of inflammatory bowel diseases (IBDs) among immigrants and in countries with historically low IBD risk is rising, implicating environmental risk factors in IBD pathogenesis. The purpose of our study was to determine the incidence rates of Crohn’s disease (CD) and ulcerative colitis (UC), among immigrants to Denmark, a high IBD incidence country, according to the country of birth and age at immigration, in comparison with the corresponding incidence rates in the Danish host population.

Methods
Using the Danish Civil Registration System, we identified all residents in Denmark with a known country of birth between January 1977 and December 2018. First-generation immigrants were persons who, along with parents, were born outside Denmark; second-generation immigrants were Danish-born persons whose parents were born outside Denmark. We recorded immigrants’ (or parents’) country of birth, age at immigration and duration of stay in Denmark. Study participants were followed for CD and UC diagnosis in the Danish National Patient Registry. Incidence rate ratios (IRRs) according to immigration status were estimated using log-linear Poisson regression analysis, and stratified by IBD prevalence in the country of birth (low, intermediate and high), and among first-generation immigrants, by age at immigration and duration of stay in Denmark.

Results
In this cohort of 9,038,025 subjects, among 1,295,518 first-generation and 208,826 second-generation immigrants eligible for inclusion, 4,805 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. The risk of IBD among first-generation immigrants reflected risk in the country of birth (low, intermediate or high, Table 1), and increased with &gt;20 years stay in Denmark (Table 2). Among second-generation immigrants, the risk of CD and UC was comparable to that in Danish natives (Table 1). Younger age at immigration did not impact IBD risk.

Conclusion
In this population-based study, the risk of IBD among first-generation immigrants reflected that in their country of birth, and increased with &gt;20 years stay in Denmark. Among second-generation immigrants, the risk was comparable to native Danes. These findings underscore the role of environmental risk factors in the aetiology of IBD. Further studies to determine risk factors for IBD among immigrants to Denmark are ongoing.
OP09 Immunomodulatory mechanisms of faecal microbiota transplantation are associated with clinical response in ulcerative colitis: early results from STOP-Colitis
Authors: Quraishi M N , Oo Y H , Beggs A , Withers D , Acharjee A , Sharma N , Manzoor S , Hart A L , Gaya D R , Loman N J , Hawkey P M , Gerasimidis K , Hansen R , Gkoutous G , Iqbal T H 
Published: January 2020

Abstract

Background
Studies of faecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. Mechanisms by which FMT modulates inflammation, however, remain unexplored. Through a prospective, open-label pilot of FMT in UC (STOP-Colitis) we conducted a sub-study to explore changes in host colonic mucosal immune cell subsets and gene expression following FMT.

Methods
Patients in this study received eight infusions of FMT over an 8-week period. Colon biopsies and blood were obtained at baseline and at the end of the study. Immunophenotyping of colonic lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) was conducted. RNA sequencing was performed on colon biopsies for differential gene expression analysis followed by multi-omic integration.

Results
Seventeen patients were recruited to this sub-study; of which, 12 completed 8 weeks of FMT per protocol. Response (reduction in MAYO score) was seen in 67% (8/12) of patients. Analysis of colonic LPMC populations revealed a significant increase in regulatory T cells (Tregs, CD4+CD25+CD127lowFoxP3+; Δ 5.02%; p &lt; 0.01), especially effector memory Treg subset (CD4+CD25+CD127-CCR7-CD45RA-; Δ 12%; p &lt; 0.001), gut homing Tregs (CD4+CD25+CD127-CCR7-CD45RA-α4+; Δ 18.55%; p &lt; 0.01) and IL-10 producing CD4 cells (Δ 2.16%; p = 0.04) in responders following FMT. Along with this, there was a significant reduction in mucosal Th17 cell (CD4+CD161+CCR6+; Δ −7.61%; p = 0.017), IL-17 producing CD4 cell (Δ −7.69%; p = 0.05) and CD8 cell (Δ -5.18%; p = 0.04) populations in FMT responders. Colonic mucosal gene expression and pathway analysis demonstrated that response to FMT was associated with significant downregulation of host antimicrobial defence response mainly REG and defensin family of anti-microbial peptides, pathogen-associated molecular pattern binding receptors, proteases, multiple MHC class II genes associated with antigen presentation and proinflammatory immune pathways. There was a significant upregulation of butanoate and propionate metabolic pathways in FMT responders. Analysis of PBMC revealed a significant increase in IL-10 producing CD4 cells suggesting that induction of peripheral immune tolerance is preferentially compartmentalised to the gut mucosa.

Conclusion
Response to FMT is associated with a significant increase in mucosal gut homing Tregs and butanoate metabolism along with a reduction in Th17 cells and multiple anti-microbial defence and proinflammatory pathways. FMT induces change in immune balance in local milieu which leads to clinical response in UC. Exploring microbial mediators in FMT which influence immunometabolism is now under investigation to underpin novel biotherapeutic approaches.