bluuebunny/crossref_metadata_2025_split huggingface dataset:
“¿Tú tienes una little pumpkin?” Mixed noun phrases in Spanish-English bilingual children and adults
Authors: Ramírez Urbaneja Desirée 
Published: December 2019

Objectives: This study investigates the switching of a noun or a determiner in mixed noun phrases, such as “ una little pumpkin,” to test predictions from two theoretical frameworks, the Matrix Language Frame model (MLF) and the Minimalist Approach (MA) and examines whether there is a difference between child and adult code-switching (CS) patterns in order to understand children’s acquisition of grammatical patterns in general. Methodology: All tokens of mixed noun phrases (NPs) were extracted from three bilingual child corpora and one bilingual adult corpus. The finite verb (matrix language) of each utterance was also analyzed to test predictions. Data and analysis: Four hundred sixty-one mixed NPs were extracted from 15 Spanish-English bilingual children and 14 Spanish-English bilingual adults. Findings: Results support both the MLF and the MA since in more than 80% of our data, the language of the determiner matched the language of the finite verb morphology and the language with the most phi features. Originality: This is the first study to compare children’s and adults’ mixed NPs, testing predictions from the MLF and MA theories. It also provides new evidence for the acquisition of CS constraints in early bilingual language development. Implications: This study demonstrates that, like adults, children’s mixed NPs are subject to grammatical constraints. Some examples show that children produce mixed NPs immediately after hearing their caregivers produce the same NP, but in one language only. This supports the conclusion that children’s mixed NP patterns follow generalized constraints and are not item-based imitations of what they hear. Limitations: Future research should more carefully examine the CS patterns of caregivers and members of the community with whom children interact to decipher the role of input. This would help answer the question of how children acquire CS patterns.
Treatment of Displaced Olecranon Fractures: A Systematic Review
Authors: Rantalaiho I. K. , Miikkulainen A. E. , Laaksonen I. E. , Äärimaa V. O. , Laimi K. A. 
Published: December 2019

Background and Aims: The incidence of olecranon fractures is rising. Displaced fractures are usually operated either by tension band wiring or plate fixation. The aim of this review is to evaluate the best current evidence on the management of displaced olecranon fractures. Materials and Methods: Randomized controlled trials were systematically gathered in May 2018 from CENTRAL, MEDLINE, Embase, CINAHL, Scopus, and PEDro databases. The methodological quality of articles was assessed according to the Cochrane Collaboration’s domain-based framework. Prospero database registration number: CRD42018096650. Results: Of 1518 identified records, finally, 5 were relevant. Four trials were found on tension band wiring: two compared tension band wiring with plate fixation (n = 108), one compared plate fixation with an olecranon memory connector (n = 40), and one trial compared tension band wiring with a modified tension band wiring called Cable Pin System (n = 62). In addition, one trial compared operative and conservative treatment in elderly (n = 19). The risk of bias was considered low in two and high in three of the trials. The follow-up time was 5–36 months, and outcome measures varied from patient-rated and physician-rated measures to radiological outcomes. In the analysis, there was no difference between tension band wiring and plate fixation. The data were insufficient for further quantitative analysis. Conclusion: No differences were found in clinical or patient-rated outcome measures between the two most frequent fixation methods (tension band wiring and plate fixation) of displaced olecranon fractures. Current data are not sufficient to evaluate other treatment methods; however, conservative treatment might serve as an option for selected patients in the elderly population.
Genome-Wide Identification of a Novel Autophagy-Related Signature for Colorectal Cancer
Authors: Huang Zhi , Liu Jie , Luo Liang , Sheng Pan , Wang Biao , Zhang Jun , Peng Sha-sha 
Published: December 2019

Background: Plenty of evidence has suggested that autophagy plays a crucial role in the biological processes of cancers. This study aimed to screen autophagy-related genes (ARGs) and establish a novel a scoring system for colorectal cancer (CRC). Methods: Autophagy-related genes sequencing data and the corresponding clinical data of CRC in The Cancer Genome Atlas were used as training data set. The GSE39582 data set from the Gene Expression Omnibus was used as validation set. An autophagy-related signature was developed in training set using univariate Cox analysis followed by stepwise multivariate Cox analysis and assessed in the validation set. Then we analyzed the function and pathways of ARGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, a prognostic nomogram combining the autophagy-related risk score and clinicopathological characteristics was developed according to multivariate Cox analysis. Results: After univariate and multivariate analysis, 3 ARGs were used to construct autophagy-related signature. The KEGG pathway analyses showed several significantly enriched oncological signatures, such as p53 signaling pathway, apoptosis, human cytomegalovirus infection, platinum drug resistance, necroptosis, and ErbB signaling pathway. Patients were divided into high- and low-risk groups, and patients with high risk had significantly shorter overall survival (OS) than low-risk patients in both training set and validation set. Furthermore, the nomogram for predicting 3- and 5-year OS was established based on autophagy-based risk score and clinicopathologic factors. The area under the curve and calibration curves indicated that the nomogram showed well accuracy of prediction. Conclusions: Our proposed autophagy-based signature has important prognostic value and may provide a promising tool for the development of personalized therapy.
Successful endovascular management of multiple mycotic aneurysms after liver transplantation – A case report and review of the literature
Authors: Ng Jun Jie , Tan Jarrod Kah Hwee , Wong Julian Chi Leung , Wee Bernard Boon Kee , Shridhar Iyer Ganpathi , Kow Alfred Wei Chieh , Madhavan Krishnakumar , Mangat Kamarjit Singh , Bonney Glenn Kunnath 
Published: December 2019

Background Mycotic vascular complications after liver transplantation are rare but can be pose a serious threat to the liver graft and the patient’s life. Mycotic complications can present as an incidental finding on routine imaging, or as haemorrhagic shock. Traditionally, these mycotic vascular complications were managed with open surgery. Method/results In this case report, we describe a patient who had developed multiple sequential mycotic aneurysms after liver transplantation which were managed successfully using endovascular and percutaneous techniques. Conclusion An endovascular approach is minimally invasive and will be the way forward in managing these mycotic vascular complications.
Key Service Improvements After the Introduction of an Integrated Orthogeriatric Service
Authors: Murphy R. P. , Reddin C. , Murphy E. P. , Waters R. , Murphy C. G. , Canavan M. 
Published: December 2019

Introduction: Models of orthogeriatric care have been shown to improve functional outcomes for patients after hip fractures and can improve compliance with best practice guidelines for hip fracture care. Methods: We evaluated improvements to key performance indicators in hip fracture care after implementation of a formal orthogeriatric service. Compliance with Irish Hip Fracture standards of care was reviewed, and additional outcomes such as length of stay, access to rehabilitation, and discharge destination were evaluated. Results: Improvements were observed in all of the hip fracture standards of care. Mean length of stay decreased from 19 to 15.5 days (mean difference 3.5 days; P < .05). A higher proportion of patients were admitted to rehabilitation (16.7% vs 7.9%, P < .05), and this happened in a timelier fashion (17.8 vs 24.8 days, P < .05). We found that less patients required convalescence post-hip fracture. Discussion: A standardized approach to integrated post-hip fracture care with orthogeriatrics has improved standards of care for patients. Conclusion: Introduction of orthogeriatric services has resulted in meaningful improvements in clinical outcomes for older people with hip fractures.
Efficacy and complications after delayed fixation of femoral neck fractures in children
Authors: Wu Chunxing , Ning Bo , Xu Ping , Song Jun , Wang Dahui 
Published: December 2019

Objective: This study evaluated the efficacy of surgery for femoral neck fractures in children after a 24-h delay and the factors affecting the risk of complications. Methods: The study included 16 children who underwent surgery after the first 24 h for femoral neck fractures. According to Delbet’s classification, there were 2 type I, 11 type II, and 3 (four hips) type III cases. The mean time from injury to surgery was 85 h (range 27–240 h). According to Garden’s classification, there were 1 type II, 14 type III, and 1 type IV (two hips) cases. Initial surgery consisted of closed reduction and hematocele drainage with a 20-mL needle tube. If the procedure failed, open reduction was performed. Internal fixation (K-wire pinning, screw) was performed after closed ( n = 9) or open ( n = 8) reduction. The results were assessed using the Ratliff criteria after a mean follow-up of 23.2 months. Patient age, type of fracture, complications, treatment, and avascular necrosis (AVN) were evaluated. Results: The results were good in 15 hips (88.2%) and fair in 2 hips (11.8%, one type II case with closed reduction and one type I case with open reduction). The most frequent complication was AVN (4 of 17; 23.5%; three Ratliff good and one fair), which was significantly related to poor outcomes. AVN occurred in one hip in the closed reduction group (Delbet’s type II, 12.5%) and in three in the open reduction group (one Delbet’s type I, 50%; two Delbet’s type II, 66.7%). There were no significant differences in the time from injury to operation (27, 54, 64, and 116 h) and AVN incidence or Ratliff criteria. Conclusions: The efficacy of delayed reduction fixation of the femoral neck was better in the closed reduction group than in the open reduction group. Fracture location closer to the femoral head and older age affected the incidence of AVN.
Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia
Authors: Döhner Konstanze , Thiede Christian , Jahn Nikolaus , Panina Ekaterina , Gambietz Agnes , Larson Richard A. , Prior Thomas W. , Marcucci Guido , Jones Dan , Krauter Jürgen , Heuser Michael , Voso Maria Teresa , Ottone Tiziana , Nomdedeu Josep F. , Mandrekar Sumithra J. , Klisovic Rebecca B. , Wei Andrew H. , Sierra Jorge , Sanz Miguel A. , Brandwein Joseph M. , de Witte Theo , Jansen Joop H. , Niederwieser Dietger , Appelbaum Frederick R. , Medeiros Bruno C. , Tallman Martin S. , Schlenk Richard F. , Ganser Arnold , Serve Hubert , Ehninger Gerhard , Amadori Sergio , Gathmann Insa , Benner Axel , Pallaud Celine , Stone Richard M. , Döhner Hartmut , Bloomfield Clara D. 
Published: December 2019

AbstractPatients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P &lt; .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.
Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation?
Authors: Ciurea Stefan O. , Kongtim Piyanuch , Varma Ankur , Rondon Gabriela , Chen Julianne , Srour Samer , Bashir Qaiser , Alousi Amin , Mehta Rohtesh , Oran Betul , Popat Uday , Hosing Chitra , Olson Amanda , Daver Naval , Konopleva Marina , Champlin Richard E. 
Published: December 2019

Abstract
The optimal conditioning regimen for older patients with acute myeloid leukemia (AML) remains unclear. In this study, we compared outcomes of AML patients &gt;60 years of age undergoing allogenic hematopoietic stem cell transplantation at our institution. All 404 consecutively treated patients received 1 of the following conditioning regimens: (1) fludarabine+melphalan 100 mg/m2 (FM100), (2) fludarabine+melphalan 140 mg/m2 (FM140), (3) fludarabine+IV busulfan AUC ≥ 5000/d × 4 d (Bu≥20000), and (4) fludarabine+IV busulfan AUC 4000/d × 4 d (Bu16000). A propensity score analysis (PSA) was used to compare outcomes between these 4 groups. Among the 4 conditioning regimens, the FM100 group had a significantly better long-term survival with 5-year progression-free survival of 49% vs 30%, 34%, and 23%, respectively. The benefit of the FM100 regimen resulted primarily from the lower nonrelapse mortality associated with this regimen, an effect more pronounced in patients with lower performance status. The PSA confirmed that FM100 was associated with better posttransplantation survival, whereas no significant differences were seen between the other regimen groups. In summary, older patients with AML benefited from a reduced-intensity conditioning regimen with lower melphalan doses (FM100), which was associated with better survival, even though it was primarily used in patients who could not receive a more intense conditioning regimen.
Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study
Authors: Guidet Bertrand , Martinet Olivier , Boulain Thierry , Philippart Francois , Poussel Jean François , Maizel Julien , Forceville Xavier , Feissel Marc , Hasselmann Michel , Heininger Alexandra , Van Aken Hugo 
Published: December 2019

Abstract
Introduction
Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients.

Methods
In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units.

Results
174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation.

Conclusion
Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups.

ClinicalTrials.gov
NCT00464204
Structure-guided mutagenesis of active site residues in the dengue virus two-component protease NS2B-NS3
Authors: Salaemae Wanisa , Junaid Muhammad , Angsuthanasombat Chanan , Katzenmeier Gerd 
Published: December 2019

AbstractBackgroundThe dengue virus two-component protease NS2B/NS3 mediates processing of the viral polyprotein precursor and is therefore an important determinant of virus replication. The enzyme is now intensively studied with a view to the structure-based development of antiviral inhibitors. Although 3-dimensional structures have now been elucidated for a number of flaviviral proteases, enzyme-substrate interactions are characterized only to a limited extend. The high selectivity of the dengue virus protease for the polyprotein precursor offers the distinct advantage of designing inhibitors with exquisite specificity for the viral enzyme. To identify important determinants of substrate binding and catalysis in the active site of the dengue virus NS3 protease, nine residues, L115, D129, G133, T134, Y150, G151, N152, S163 and I165, located within the S1 and S2 pockets of the enzyme were targeted by alanine substitution mutagenesis and effects on enzyme activity were fluorometrically assayed.MethodsAlanine substitutions were introduced by site-directed mutagenesis at residues L115, D129, G133, T134, Y150, G151, N152, S163 and I165 and recombinant proteins were purified from overexpressingE. coli. Effects of these substitutions on enzymatic activity of the NS3 protease were assayed by fluorescence release from the synthetic model substrate GRR-amc and kinetic parametersKm,kcatandkcat/Kmwere determined.ResultsKinetic data for mutant derivatives in the active site of the dengue virus NS3 protease were essentially in agreement with a functional role of the selected residues for substrate binding and/or catalysis. Only the L115A mutant displayed activity comparable to the wild-type enzyme, whereas mutation of residues Y150 and G151 to alanine completely abrogated enzyme activity. A G133A mutant had an approximately 10-fold reduced catalytic efficiency thus suggesting a critical role for this residue seemingly as part of the oxyanion binding hole.ConclusionsKinetic data obtained for mutants in the NS3 protease have confirmed predictions for the conformation of the active site S1 and S2 pockets based on earlier observations. The data presented herein will be useful to further explore structure-activity relationships of the flaviviral proteases important for the structure-guided design of novel antiviral therapeutics.
Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression
Authors: Xu Xiaojiang , Hoang Stephen , Mayo Marty W , Bekiranov Stefan 
Published: December 2019

AbstractBackgroundIn the last decade, biochemical studies have revealed that epigenetic modifications including histone modifications, histone variants and DNA methylation form a complex network that regulate the state of chromatin and processes that depend on it including transcription and DNA replication. Currently, a large number of these epigenetic modifications are being mapped in a variety of cell lines at different stages of development using high throughput sequencing by members of the ENCODE consortium, the NIH Roadmap Epigenomics Program and the Human Epigenome Project. An extremely promising and underexplored area of research is the application of machine learning methods, which are designed to construct predictive network models, to these large-scale epigenomic data sets.ResultsUsing a ChIP-Seq data set of 20 histone lysine and arginine methylations and histone variant H2A.Z in human CD4+T-cells, we built predictive models of gene expression as a function of histone modification/variant levels using Multilinear (ML) Regression and Multivariate Adaptive Regression Splines (MARS). Along with extensive crosstalk among the 20 histone methylations, we found H4R3me2 was the most and second most globally repressive histone methylation among the 20 studied in the ML and MARS models, respectively. In support of our finding, a number of experimental studies show that PRMT5-catalyzed symmetric dimethylation of H4R3 is associated with repression of gene expression. This includes a recent study, which demonstrated that H4R3me2 is required for DNMT3A-mediated DNA methylation--a known global repressor of gene expression.ConclusionIn stark contrast to univariate analysis of the relationship between H4R3me2 and gene expression levels, our study showed that the regulatory role of some modifications like H4R3me2 is masked by confounding variables, but can be elucidated by multivariate/systems-level approaches.
Predicting enzyme targets for cancer drugs by profiling human Metabolic reactions in NCI-60 cell lines
Authors: Li Limin , Zhou Xiaobo , Ching Wai-Ki , Wang Ping 
Published: December 2019

Abstract

Background
Drugs can influence the whole metabolic system by targeting enzymes which catalyze metabolic reactions. The existence of interactions between drugs and metabolic reactions suggests a potential way to discover drug targets.

Results
In this paper, we present a computational method to predict new targets for approved anti-cancer drugs by exploring drug-reaction interactions. We construct a Drug-Reaction Network to provide a global view of drug-reaction interactions and drug-pathway interactions. The recent reconstruction of the human metabolic network and development of flux analysis approaches make it possible to predict each metabolic reaction's cell line-specific flux state based on the cell line-specific gene expressions. We first profile each reaction by its flux states in NCI-60 cancer cell lines, and then propose a kernel k-nearest neighbor model to predict related metabolic reactions and enzyme targets for approved cancer drugs. We also integrate the target structure data with reaction flux profiles to predict drug targets and the area under curves can reach 0.92.

Conclusions
The cross validations using the methods with and without metabolic network indicate that the former method is significantly better than the latter. Further experiments show the synergism of reaction flux profiles and target structure for drug target prediction. It also implies the significant contribution of metabolic network to predict drug targets. Finally, we apply our method to predict new reactions and possible enzyme targets for cancer drugs.