bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Preoperative Opioid Use and Prolonged Postoperative Opioid Use Following Total Ankle Arthroplasty
Authors: DeMik David E. , Cychosz Chris C. , Bedard Nicholas A. , Barton Cameron , An Qiang , Duchman Kyle R. 
Published: January 2020

Background: Perioperative opioid consumption has received a great deal of recent attention. However, perioperative opioid utilization in the total ankle arthroplasty (TAA) population has not been well studied. We sought to identify factors associated with postoperative opioid use following TAA. Methods: The PearlDiver Research Program was used to query the Humana, Inc, administrative claims database from 2007 to 2017 for patients undergoing TAA. Additional variables of interest were identified using ICD-9 and ICD-10 codes. Preoperative opioid use was defined as having filled an opioid prescription in the 3 months before TAA. Prescription opioid claims data were tracked for 12 months postoperatively. Risk ratios (RRs) were calculated and multivariate analysis was performed at 3, 6, and 12 months postoperatively. Results: A total of 544 patients who underwent TAA were identified, with 180 (33.1%) filling an opioid prescription preoperatively. Those filling prescriptions preoperatively had a significantly greater risk for postoperative opioid use compared to those not taking opioids (RR: 4.36 [95% confidence interval (CI): 2.80-6.80] at 12 months). Anxiety or depression (RR: 2.27 [1.44-3.59]), low back pain (LBP) (RR: 2.27 [1.50-3.42]), and fibromyalgia (RR: 2.15 [1.42-3.28]) were also found to increase the risk of taking opioids at 12 months postoperatively. Multivariate analysis found preoperative opioid use to be the strongest predictor of postoperative opioid use. Conclusions: Nearly one-third of patients filled an opioid prescription within 3 months of TAA, and filling a prescription preoperatively was the strongest factor associated with postoperative opioid use. Fibromyalgia, depression or anxiety, and LBP were also associated with an increased likelihood of postoperative opioid use. Level of Evidence: Level III, retrospective cohort study.
Dnmt3a loss and Idh2 neomorphic mutations mutually potentiate malignant hematopoiesis
Authors: Zhang Xiaotian , Wang Xinyu , Wang Xue Qing David , Su Jianzhong , Putluri Nagireddy , Zhou Ting , Qu Ying , Jeong Mira , Guzman Anna , Rosas Carina , Huang Yun , Sreekumar Arun , Li Wei , Goodell Margaret A. 
Published: January 2020

Abstract
Mutations in the epigenetic regulators DNMT3A and IDH1/2 co-occur in patients with acute myeloid leukemia and lymphoma. In this study, these 2 epigenetic mutations cooperated to induce leukemia. Leukemia-initiating cells from Dnmt3a−/− mice that express an IDH2 neomorphic mutant have a megakaryocyte-erythroid progenitor–like immunophenotype, activate a stem-cell–like gene signature, and repress differentiated progenitor genes. We observed an epigenomic dysregulation with the gain of repressive H3K9 trimethylation and loss of H3K9 acetylation in diseased mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). HDAC inhibitors rapidly reversed the H3K9 methylation/acetylation imbalance in diseased mouse HSPCs while reducing the leukemia burden. In addition, using targeted metabolomic profiling for the first time in mouse leukemia models, we also showed that prostaglandin E2 is overproduced in double-mutant HSPCs, rendering them sensitive to prostaglandin synthesis inhibition. These data revealed that Dnmt3a and Idh2 mutations are synergistic events in leukemogenesis and that HSPCs carrying both mutations are sensitive to induced differentiation by the inhibition of both prostaglandin synthesis and HDAC, which may reveal new therapeutic opportunities for patients carrying IDH1/2 mutations.
von Willebrand factor binding to myosin assists in coagulation
Authors: Flood Veronica H. , Slobodianuk Tricia L. , Keesler Daniel , Lohmeier Hannah K. , Fahs Scot , Zhang Liyun , Simpson Pippa , Montgomery Robert R. 
Published: January 2020

Abstractvon Willebrand factor (VWF) binds to platelets and collagen as a means of facilitating coagulation at sites of injury. Recent evidence has shown that myosin can serve as a surface for thrombin generation and binds to activated factor V and factor X. We studied whether VWF can also bind myosin as a means of bringing factor VIII (FVIII) to sites of clot formation. A myosin-binding assay was developed using skeletal muscle myosin to measure VWF binding, and plasma-derived and recombinant VWF containing molecular disruptions at key VWF sites were tested. Competition assays were performed using anti-VWF antibodies. FVIII binding to myosin was measured using a chromogenic FVIII substrate. Thrombin generation was measured using a fluorogenic substrate with and without myosin. Wild-type recombinant VWF and human plasma VWF from healthy controls bound myosin, whereas plasma lacking VWF exhibited no detectable myosin binding. Binding was multimer dependent and blocked by anti-VWF A1 domain antibodies or A1 domain VWF variants. The specific residues involved in myosin binding were similar, but not identical, to those required for collagen IV binding. FVIII did not bind myosin directly, but FVIII activity was detected when VWF and FVIII were bound to myosin. Myosin enhanced thrombin generation in platelet-poor plasma, although no difference was detected with the addition of myosin to platelet-rich plasma. Myosin may help to facilitate delivery of FVIII to sites of injury and indirectly accelerate thrombin generation by providing a surface for VWF binding in the setting of trauma and myosin exposure.
Undetectable peripheral blood MRD should be the goal of venetoclax in CLL, but attainment plateaus after 24 months
Authors: Lew Thomas E. , Anderson Mary Ann , Lin Victor S. , Handunnetti Sasanka M. , Came Neil A. , Blombery Piers , Westerman David A. , Wall Meaghan , Tam Constantine S. , Roberts Andrew W. , Seymour John F. 
Published: January 2020

Abstract
The highly selective BCL2 inhibitor venetoclax achieves deep responses in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including undetectable minimal residual disease (uMRD). We retrospectively reviewed 62 patients with CLL treated with venetoclax to investigate the performance of peripheral blood (PB) compared with bone marrow (BM) assessment of MRD; the kinetics, clinicopathological associations, and longer-term outcomes of uMRD attainment and recrudescence; and the ability of venetoclax dose escalation to deepen responses. Among 16 patients who achieved PB uMRD and had contemporaneous BM assessments, 13 (81%) had confirmed BM uMRD, and patients with PB uMRD had outcomes at least as favorable as those with BM uMRD for time to progression, overall survival, and MRD recrudescence. Excluding 2 patients lacking earlier assessment, the median time to PB uMRD was 18 (range, 5-26) months, with 90% of instances achieved by 24 months. There was no new PB uMRD attainment after 24 months without treatment intensification. The dominant association with earlier attainment of uMRD was concurrent rituximab (P = .012). Complex karyotype was associated with inferior uMRD attainment after 12 months of therapy (P = .015), and patients attaining uMRD whose disease harbored TP53 abnormalities demonstrated a trend toward earlier recrudescence (P = .089). Of patients who received venetoclax dose escalations, 4 (27%) of 15 achieved improvements in response. For patients with R/R CLL receiving venetoclax, PB uMRD commonly correlates with BM uMRD and is associated with a comparable longer-term prognosis. Concurrent rituximab augments uMRD attainment, but dose escalation and further treatment beyond 24 months infrequently deepen responses.
Automatic construction of metabolic models with enzyme constraints
Authors: Bekiaris Pavlos Stephanos , Klamt Steffen 
Published: January 2020

Abstract
Background
In order to improve the accuracy of constraint-based metabolic models, several approaches have been developed which intend to integrate additional biological information. Two of these methods, MOMENT and GECKO, incorporate enzymatic (kcat) parameters and enzyme mass constraints to further constrain the space of feasible metabolic flux distributions. While both methods have been proven to deliver useful extensions of metabolic models, they may considerably increase size and complexity of the models and there is currently no tool available to fully automate generation and calibration of such enzyme-constrained models from given stoichiometric models.

Results
In this work we present three major developments. We first conceived short MOMENT (sMOMENT), a simplified version of the MOMENT approach, which yields the same predictions as MOMENT but requires significantly fewer variables and enables direct inclusion of the relevant enzyme constraints in the standard representation of a constraint-based model. When measurements of enzyme concentrations are available, these can be included as well leading in the extreme case, where all enzyme concentrations are known, to a model representation that is analogous to the GECKO approach. Second, we developed the AutoPACMEN toolbox which allows an almost fully automated creation of sMOMENT-enhanced stoichiometric metabolic models. In particular, this includes the automatic read-out and processing of relevant enzymatic data from different databases and the reconfiguration of the stoichiometric model with embedded enzymatic constraints. Additionally, tools have been developed to adjust (kcat and enzyme pool) parameters of sMOMENT models based on given flux data. We finally applied the new sMOMENT approach and the AutoPACMEN toolbox to generate an enzyme-constrained version of the E. coli genome-scale model iJO1366 and analyze its key properties and differences with the standard model. In particular, we show that the enzyme constraints improve flux predictions (e.g., explaining overflow metabolism and other metabolic switches) and demonstrate, for the first time, that these constraints can markedly change the spectrum of metabolic engineering strategies for different target products.

Conclusions
The methodological and tool developments presented herein pave the way for a simplified and routine construction and analysis of enzyme-constrained metabolic models.
Downregulation of lncRNA DANCR promotes osteogenic differentiation of periodontal ligament stem cells
Authors: Wang Zhuo , Huang Yuanliang , Tan Luanjun 
Published: January 2020

Abstract
Background
Long non-coding RNAs (lncRNAs) have been widely known to have an appreciable effect in physiology and pathology. In tooth regeneration, periodontal ligament stem cells (PDLSCs) are regarded as a key effector, whereas, how lncRNA acts in the osteogenic differentiation of PDLSCs have not been completely understood. This study aims to find out the relationship between lncRNA DANCR and the proliferation and osteogenic differentiation of PDLSCs.

Methods
Microarray was used to observe the different expression of lncRNAs in differentiated and undifferentiated PDLSCs. And then osteogenic-related lncRNA, DANCR was screened out. Its effects on proliferation and osteogenic differentiation was explored by constructing an overexpression and inhibition model. qRT-PCR was used to detect the mRNA expression of osteogenesis related genes. MTT assay was performed to assess the effects of DANCR on cell growth curve. To quantify the effects of DANCR on osteogenic differentiation of PDLSCs, ALP staining and alizarin red was performed in basic culture medium and osteogenic medium. Data were statistically processed.

Results
Compared with the undifferentiated PDLSCs, the alizarin red staining level was higher in differentiated PDLSCs. And the expressions of osteogenic differentiation marker genes Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein (BMP-2) were significantly increased in the differentiated PDLSCs. Furthermore, we noticed that comparing with control groups, the expression of lncRNA DANCR decreases markedly in osteogenically induced PDLSCs. DANCR promoted proliferation of PDLSCs, as evidenced by cell viability. Further investigation has proven that the downregulation of DANCR shows in the calcium sediment forming, alkaline phosphatase (ALP) activation and some osteogenic-related gene markers’ upregulation including Runx2, OCN and BMP-2, which finally results in the osteogenic differentiation of PDLSCs following the transfection and induction. Conversely, DANCR upregulation was shown to repress the osteogenic differentiation potential of PDLSCs.

Conclusions
The osteogenic differentiation of PDLSCs has proven to related to the down regulation of lncRNA DANCR. And this paper throws light on the effects of DANCR in the process of PDLSCs’ osteogenic differentiation.
Changes in life history traits and transcriptional regulation of Coccinellini ladybirds in using alternative prey
Authors: Chen Mei-Lan , Huang Yu-Hao , Qiu Bo-Yuan , Chen Pei-Tao , Du Xue-Yong , Li Hao-Sen , Pang Hong 
Published: January 2020

Abstract
Background
Ladybird beetles (Coleoptera, Coccinellidae) are highly diverse in their feeding habits. Most of them are specialist feeders, while some can have a broad spectrum of prey. As a representative group of generalists, the tribe Coccinellini includes many aphidophagous species, but members of this tribe also feed on other hemipterous insects including coccids, psyllids and whiteflies. As a result, several species are effective biological control agents or invasive species with serious non-target effects. Despite their economic importance, relatively little is known about how they adapt to new prey.

Results
In this study, comparisons of the life history traits and transcriptomes of ladybirds fed initial (aphids) and alternative prey (mealybugs) were performed in three Coccinellini species. The use of alternative prey greatly decreased performance, implied by the significantly prolonged development time and decreased survival rate and adult weight. Prey shifts resulted in a set of differentially expressed genes encoding chemosensory proteins and digestive and detoxifying enzymes.

Conclusions
Our results suggest that these generalists do not perform well when they use alternative prey as the sole nutrition source. Although their capacity for predation might have created an opportunity to use varied prey, they must adapt to physiological obstacles including chemosensing, digestion and detoxification in response to a prey shift. These findings challenge the effect of Coccinellini predators on the biological control of non-aphid pests and suggest the possibility of non-target attacks by so-called specialists.
miRNA and circRNA expression patterns in mouse brain during toxoplasmosis development
Authors: Zhou Chun-Xue , Ai Kang , Huang Cui-Qin , Guo Jing-Jing , Cong Hua , He Shen-Yi , Zhu Xing-Quan 
Published: January 2020

AbstractBackgroundIncreasing evidence has shown that circular RNAs (circRNAs) are involved in neurodegenerative disorders, but their roles in neurological toxoplasmosis are yet to know. This study examined miRNA and circRNA expressions in mouse brain following oral infection withT. gondiiPru strain.ResultsTotal RNA extracted from acutely infected (11 days post infection (DPI)), chronically infected (35 DPI) and uninfected mouse brain samples were subjected to genome-wide small RNA sequencing. In the acutely infected mice, 9 circRNAs and 20 miRNAs were upregulated, whereas 67 circRNAs and 28 miRNAs were downregulated. In the chronically infected mice, 2 circRNAs and 42 miRNAs were upregulated, whereas 1 circRNA and 29 miRNAs were downregulated. Gene ontology analysis predicted that the host genes that produced the dysregulated circRNAs in the acutely infected brain were primarily involved in response to stimulus and ion binding activities. Furthermore, predictive interaction networks of circRNA-miRNA and miRNA-mRNA were constructed based on genome-wide transcriptome sequencing and computational analyses, which might suggest the putative functions of miRNAs and circRNAs as a large class of post-transcriptional regulators.ConclusionsThese findings will shed light on circRNA-miRNA interactions during the pathogenesis of toxoplasmosis, and they will lay solid foundation for studying the potential regulation roles of miRNAs and circRNAs inT. gondiiinduced pathogenesis.
Comparisons of microbiological characteristics and antibiotic resistance of Klebsiella pneumoniae isolates from urban rodents, shrews, and healthy people
Authors: Zhong Xue-shan , Li Yong-zhi , Ge Jing , Xiao Gang , Mo Yun , Wen Yu-qi , Liu Jing-ping , Xiong Yi-quan , Qiu Min , Huo Shu-ting , Cheng Ming-ji , Chen Qing 
Published: January 2020

Abstract
Background
The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people.

Results
K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum β-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult.

Conclusions
Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.
Comparative study of Revogene GBS LB assay and GeneXpert GBS LB assay for the detection of group B Streptococcus in prenatal screening samples
Authors: Choera Tsokyi , Jung-Hynes Brittney , Chen Derrick J. 
Published: January 2020

Abstract
Background
Group B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC therefore recommends GBS screening for all pregnant women at 35–37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women.

Method
In this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, Revogene GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsin’s clinical microbiology laboratory for GBS testing.

Results
We found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with a positive percent agreement of 98.0% and a negative percent agreement of 96.5% between the Revogene GBS LB assay and the GeneXpert GBS LB assay.

Conclusion
Overall, we report that both assays perform well for the detection of GBS colonization in pregnant women.
Provider volume and maternal complications after Caesarean section: results from a population-based study
Authors: Leonard Philip S. J. , Crouse Dan L. , Boudreau Jonathan G. , Gupta Neeru , McDonald James T. 
Published: January 2020

Abstract
Background
A large literature search suggests a relationship between hospital/surgeon caseload volume and surgical complications. In this study, we describe associations between post-operative maternal complications following Caesarean section and provider caseload volume, provider years since graduation, and provider specialization, while adjusting for hospital volumes and patient characteristics.

Methods
Our analysis is based on population-based discharge abstract data for the period of April 2004 to March 2014, linked to patient and physician universal coverage registry data. We consider all hospital admissions (N = 20,914) in New Brunswick, Canada, where a Caesarean Section surgery was recorded, as identified by a Canadian Classification of Health Intervention code of 5.MD.60.XX. We ran logistic regression models to identify the odds of occurrence of post-surgical complications during the hospital stay.

Results
Roughly 2.6% of admissions had at least one of the following groups of complications: disseminated intravascular coagulation, postpartum sepsis, postpartum hemorrhage, and postpartum infection. The likelihood of complication was negatively associated with provider volume and provider years of experience, and positively associated with having a specialization other than maternal-fetal medicine or obstetrics and gynecology.

Conclusions
Our results suggest that measures of physician training and experience are associated with the likelihood of Caesarean Section complications. In the context of a rural province deciding on the number of rural hospitals to keep open, this suggests a trade off between the benefits of increased volume versus the increased travel time for patients.
Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?
Authors: Moore Assaf , Hikri Elad , Goshen-Lago Tal , Barkan Tamar , Morgenstern Sara , Brook Elena , Maderer Annett , Roth Wilfried , Gordon Noa , Kashtan Hanoch , Brenner Baruch , Moehler Markus , Aharon Irit Ben 
Published: January 2020

Abstract
Objective
Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC.

Methods
Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records.

Results
Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002).

Conclusion
Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.