bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting
Authors: Takeda Kazuyoshi , Nakayama Masafumi , Hayakawa Yoshihiro , Kojima Yuko , Ikeda Hiroaki , Imai Naoko , Ogasawara Kouetsu , Okumura Ko , Thomas David M. , Smyth Mark J. 
Published: February 2017

AbstractGenetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution.
MnGa-based fully perpendicular magnetic tunnel junctions with ultrathin Co2MnSi interlayers
Authors: Mao Siwei , Lu Jun , Zhao Xupeng , Wang Xiaolei , Wei Dahai , Liu Jian , Xia Jianbai , Zhao Jianhua 
Published: February 2017

AbstractBecause tetragonal structured MnGa alloy has intrinsic (not interface induced) giant perpendicular magnetic anisotropy (PMA), ultra-low damping constant and high spin polarization, it is predicted to be a kind of suitable magnetic electrode candidate in the perpendicular magnetic tunnel junction (p-MTJ) for high density spin transfer torque magnetic random access memory (STT-MRAM) applications. However, p-MTJs with both bottom and top MnGa electrodes have not been achieved yet, since high quality perpendicular magnetic MnGa films can hardly be obtained on the MgO barrier due to large lattice mismatch and surface energy difference between them. Here, a MnGa-based fully p-MTJ with the structure of MnGa/Co2MnSi/MgO/Co2MnSi/MnGa is investigated. As a result, the multilayer is with high crystalline quality, and both the top and bottom MnGa electrodes show well PMA. Meanwhile, a distinct tunneling magnetoresistance (TMR) ratio of 65% at 10 K is achieved. Ultrathin Co2MnSi films are used to optimize the interface quality between MnGa and MgO barrier. A strong antiferromagnetic coupling in MnGa/Co2MnSi bilayer is confirmed with the interfacial exchange coupling constant of −5erg/cm2. This work proposes a novel p-MTJ structure for the future STT-MRAM progress.
Genome-wide screening and characterization of long non-coding RNAs involved in flowering development of trifoliate orange (Poncirus trifoliata L. Raf.)
Authors: Wang Chen-Yang , Liu Sheng-Rui , Zhang Xiao-Yu , Ma Yu-Jiao , Hu Chun-Gen , Zhang Jin-Zhi 
Published: February 2017

AbstractLong non-coding RNAs (lncRNAs) have been demonstrated to play critical regulatory roles in post-transcriptional and transcriptional regulation in Arabidopsis. However, lncRNAs and their functional roles remain poorly characterized in woody plants, including citrus. To identify lncRNAs and investigate their role in citrus flowering, paired-end strand-specific RNA sequencing was performed for precocious trifoliate orange and its wild-type counterpart. A total of 6,584 potential lncRNAs were identified, 51.6% of which were from intergenic regions. Additionally, 555 lncRNAs were significantly up-regulated and 276 lncRNAs were down-regulated in precocious trifoliate orange, indicating that lncRNAs could be involved in the regulation of trifoliate orange flowering. Comparisons between lncRNAs and coding genes indicated that lncRNAs tend to have shorter transcripts and lower expression levels and that they display significant expression specificity. More importantly, 59 and 7 lncRNAs were identified as putative targets and target mimics of citrus miRNAs, respectively. In addition, the targets of Pt-miR156 and Pt-miR396 were confirmed using the regional amplification reverse-transcription polymerase chain reaction method. Furthermore, overexpression of Pt-miR156a1 and Pt-miR156a1 in Arabidopsis resulted in an extended juvenile phase, short siliques, and smaller leaves in transgenic plants compared with control plants. These findings provide important insight regarding citrus lncRNAs, thus enabling in-depth functional analyses.
Transcriptional mechanism of vascular endothelial growth factor-induced expression of protein kinase CβII in chronic lymphocytic leukaemia cells
Authors: Al-Sanabra Ola , Duckworth Andrew D. , Glenn Mark A. , Brown Benjamin R. B. , Angelillo Piera , Lee Kelvin , Herbert John , Falciani Francesco , Kalakonda Nagesh , Slupsky Joseph R. 
Published: February 2017

AbstractA key feature of chronic lymphocytic leukaemia (CLL) cells is overexpressed protein kinase CβII (PKCβII), an S/T kinase important in the pathogenesis of this and other B cell malignancies. The mechanisms contributing to enhanced transcription of the gene coding for PKCβII, PRKCB, in CLL cells remain poorly described, but could be important because of potential insight into how the phenotype of these cells is regulated. Here, we show that SP1 is the major driver of PKCβII expression in CLL cells where enhanced association of this transcription factor with the PRKCB promoter is likely because of the presence of histone marks permissive of gene activation. We also show how vascular endothelial growth factor (VEGF) regulates PRKCB promoter function in CLL cells, stimulating PKCβ gene transcription via increased association of SP1 and decreased association of STAT3. Taken together, these results are the first to demonstrate a clear role for SP1 in the up regulation of PKCβII expression in CLL cells, and the first to link SP1 with the pathogenesis of this and potentially other B cell malignancies where PKCβII is overexpressed.
An upper limit of Cr-doping level to Retain Zero-strain Characteristics of Li4Ti5O12 Anode Material for Li-ion Batteries
Authors: Song Hannah , Jeong Tae-Gyung , Yun Su-Won , Lee Eun-Kyung , Park Shin-Ae , Kim Yong-Tae 
Published: February 2017

AbstractSince Li4Ti5O12 as a promising anode material in lithium-ion batteries (LIBs) has a poor rate performance due to low electronic conductivity, a doping of Li4Ti5O12 with heterogeneous atoms has been considered to overcome this problem. Herein, we report that there is an upper limit of doping level to maintain the zero strain characteristics of Li4Ti5O12 lattice during charge/discharge process. By using synchrotron studies, it was revealed that the Li+ diffusivity was maximized at a certain doping level for which the conductivity was markedly increased with maintaining the zero strain characteristics. However, with more doses of dopants over the upper limit, the lattice shrank and therefore the Li+ diffusivity decreased, although the electronic conductivity was further increased in comparison with the optimal doping level.
High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence
Authors: Nordby Yngve , Richardsen Elin , Rakaee Mehrdad , Ness Nora , Donnem Tom , Patel Hiten R. H. , Busund Lill-Tove , Bremnes Roy M. , Andersen Sigve 
Published: February 2017

AbstractDue to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.
The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization
Authors: Romero-López Cristina , Barroso-delJesus Alicia , Berzal-Herranz Alfredo 
Published: February 2017

AbstractThe RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3′UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2′-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome.
Surgical Management of Congenital Abdominal Wall Defects in Germany: A Population-Based Study and Comparison with Literature Reports
Authors: Dietrich Janine , Zeidler Jan , Blaser Jochen , Gosemann Jan , Lacher Martin , Ure Benno , Dingemann Carmen 
Published: February 2017

Introduction We aimed to analyze for the first time the characteristics, treatment modalities, and outcomes in infants with congenital abdominal wall defects (CAWDs) in Germany and to compare the results with current literature reports.
Patients and Methods Data of a health insurance covering approximately 10% of the German population were analyzed. Patients who had undergone CAWD closure during a period of nearly 6 years were included. Surgical approach was categorized into primary versus secondary closure. Complications were defined as any reintervention within 1 year after initial treatment.
Results Patients with gastroschisis were treated in 24 centers, newborns with omphalocele in 34 centers. There was no mortality, and the type of surgical approach had no significant impact on the incidence of complications in both gastroschisis and omphalocele. Out of 39 patients with gastroschisis, 72% had undergone primary closure being associated with a shorter duration of ventilation (p = 0.003) and hospitalization (p < 0.001). Out of 54 patients with omphalocele, 54% had undergone secondary closure, whereas modality of management did not affect duration of ventilation and hospitalization. Although heterogeneous, data of the current literature were comparable to those of this study.
Conclusion Unbiased data demonstrate for the first time that the quality of the current surgical management of newborns with CAWD across Germany is excellent. There was no correlation of complications with the method of closure in gastroschisis and omphalocele.
An improved assembly of the loblolly pine mega-genome using long-read single-molecule sequencing
Authors: Zimin Aleksey V. , Stevens Kristian A. , Crepeau Marc W. , Puiu Daniela , Wegrzyn Jill L. , Yorke James A. , Langley Charles H. , Neale David B. , Salzberg Steven L. 
Published: February 2017

Abstract
The 22-gigabase genome of loblolly pine (Pinus taeda) is one of the largest ever sequenced. The draft assembly published in 2014 was built entirely from short Illumina reads, with lengths ranging from 100 to 250 base pairs (bp). The assembly was quite fragmented, containing over 11 million contigs whose weighted average (N50) size was 8206 bp. To improve this result, we generated approximately 12-fold coverage in long reads using the Single Molecule Real Time sequencing technology developed at Pacific Biosciences. We assembled the long and short reads together using the MaSuRCA mega-reads assembly algorithm, which produced a substantially better assembly, P. taeda version 2.0. The new assembly has an N50 contig size of 25 361, more than three times as large as achieved in the original assembly, and an N50 scaffold size of 107 821, 61% larger than the previous assembly.
Draft genome of the honey bee ectoparasitic mite, Tropilaelaps mercedesae, is shaped by the parasitic life history
Authors: Dong Xiaofeng , Armstrong Stuart D. , Xia Dong , Makepeace Benjamin L. , Darby Alistair C. , Kadowaki Tatsuhiko 
Published: February 2017

Abstract
The number of managed honey bee colonies has considerably decreased in many developed countries in recent years and ectoparasitic mites are considered as major threats to honey bee colonies and health. However, their general biology remains poorly understood. We sequenced the genome of Tropilaelaps mercedesae, the prevalent ectoparasitic mite infesting honey bees in Asia, and predicted 15 190 protein-coding genes that were well supported by the mite transcriptomes and proteomic data. Although amino acid substitutions have been accelerated within the conserved core genes of two mites,T. mercedesae and Metaseiulus occidentalis, T. mercedesae has undergone the least gene family expansion and contraction between the seven arthropods we tested. The number of sensory system genes has been dramatically reduced, but T. mercedesae contains all gene sets required to detoxify xenobiotics. T. mercedesae is closely associated with a symbiotic bacterium (Rickettsiella grylli-like) and Deformed Wing Virus, the most prevalent honey bee virus. T. mercedesae has a very specialized life history and habitat as the ectoparasitic mite strictly depends on the honey bee inside a stable colony. Thus, comparison of the genome and transcriptome sequences with those of a tick and free-living mites has revealed the specific features of the genome shaped by interaction with the honey bee and colony environment. Genome and transcriptome sequences of T. mercedesae, as well as Varroa destructor (another globally prevalent ectoparasitic mite of honey bee), not only provide insights into the mite biology, but may also help to develop measures to control the most serious pests of the honey bee.
Meaningful use of health information technology and declines in in-hospital adverse drug events
Authors: Furukawa Michael F , Spector William D , Rhona Limcangco M , Encinosa William E 
Published: February 2017

Abstract
Objective: Nationwide initiatives have promoted greater adoption of health information technology as a means to reduce adverse drug events (ADEs). Hospital adoption of electronic health records with Meaningful Use (MU) capabilities expected to improve medication safety has grown rapidly. However, evidence that MU capabilities are associated with declines in in-hospital ADEs is lacking.
Methods: Data came from the 2010–2013 Medicare Patient Safety Monitoring System and the 2008–2013 Healthcare Information and Management Systems Society (HIMSS) Analytics Database. Two-level random intercept logistic regression was used to estimate the association of MU capabilities and occurrence of ADEs, adjusting for patient characteristics, hospital characteristics, and year of observation.
Results: Rates of in-hospital ADEs declined by 19% from 2010 to 2013. Adoption of MU capabilities was associated with 11% lower odds of an ADE (95% confidence interval [CI], 0.84–0.96). Interoperability capability was associated with 19% lower odds of an ADE (95% CI, 0.67- 0.98). Adoption of MU capabilities explained 22% of the observed reduction in ADEs, or 67,000 fewer ADEs averted by MU.
Discussion: Concurrent with the rapid uptake of MU and interoperability, occurrence of in-hospital ADEs declined significantly from 2010 to 2013. MU capabilities and interoperability were associated with lower occurrence of ADEs, but the effects did not vary by experience with MU. About one-fifth of the decline in ADEs from 2010 to 2013 was attributable to MU capabilities.
Conclusion: Findings support the contention that adoption of MU capabilities and interoperability spurred by the Health Information Technology for Economic and Clinical Health Act contributed in part to the recent decline in ADEs.
Development of an automated assessment tool for MedWatch reports in the FDA adverse event reporting system
Authors: Han Lichy , Ball Robert , Pamer Carol A , Altman Russ B , Proestel Scott 
Published: February 2017

Abstract
Objective: As the US Food and Drug Administration (FDA) receives over a million adverse event reports associated with medication use every year, a system is needed to aid FDA safety evaluators in identifying reports most likely to demonstrate causal relationships to the suspect medications. We combined text mining with machine learning to construct and evaluate such a system to identify medication-related adverse event reports.
Methods: FDA safety evaluators assessed 326 reports for medication-related causality. We engineered features from these reports and constructed random forest, L1 regularized logistic regression, and support vector machine models. We evaluated model accuracy and further assessed utility by generating report rankings that represented a prioritized report review process.
Results: Our random forest model showed the best performance in report ranking and accuracy, with an area under the receiver operating characteristic curve of 0.66. The generated report ordering assigns reports with a higher probability of medication-related causality a higher rank and is significantly correlated to a perfect report ordering, with a Kendall’s tau of 0.24 (P = .002).
Conclusion: Our models produced prioritized report orderings that enable FDA safety evaluators to focus on reports that are more likely to contain valuable medication-related adverse event information. Applying our models to all FDA adverse event reports has the potential to streamline the manual review process and greatly reduce reviewer workload.
Diagnostic and therapeutic considerations in patients with hypogammaglobulinemia after rituximab therapy
Authors: Kado Ruba , Sanders Georgiana , McCune W. Joseph 
Published: February 2017

Purpose of review
There are no established guidelines for evaluating and treating hypogammaglobulinemia in patients with rheumatic disease who receive B-cell depleting agents. The purpose of this article is to review findings in the work-up and treatment of common variable immunodeficiency (CVID) that can guide our evaluation of patients with autoimmune disease who develop hypogammaglobulinemia after rituximab/B-cell depleting therapy.

Recent findings
Infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. However, not all patients who develop hypogammaglobulinemia are at increased risk of developing infection after B-cell depleting therapy. Recent consensus statements have helped refine the diagnosis of impaired immune responses in patients with CVID, and can provide guidance for the diagnostic work-up and therapeutic decision making for patients with secondary drug induced hypogammaglobulinemia.

Summary
Based on findings in studies of CVID, assessment of vaccine response in patients with hypogammglogulinemia after rituximab therapy in the setting of recurrent infections can help predict propensity for infection and thus guide decision making with regards to intravenous immunoglobulin supplementation and retreatment with rituximab.
Growing Rods Are an Effective Fusionless Method of Controlling Early-Onset Scoliosis Associated With Neurofibromatosis Type 1 (NF1): A Multicenter Retrospective Case Series
Authors: Jain Viral V. , Berry Chirag A. , Crawford Alvin H. , Emans John B. , Sponseller Paul D. 
Published: February 2017

Background:
Spinal deformities associated with neurofibromatosis type 1 (NF1) often have an early onset. These curves frequently develop dysplastic features. Rapid progression is common, and is often difficult to control with casting or bracing. Spinal fusion at a young age can potentially interfere with chest and trunk growth. Growing rods (GRs) have been used in early-onset scoliosis (EOS) effectively. The purpose of this study was to evaluate GR use in NF1.

Methods:
Retrospective data collection was performed from a multicenter EOS database with additional patients from our own institute. Each patient had a genetic diagnosis of NF1 and was treated with GR. Results were compared with reported results of GR in EOS in the literature.

Results:
Fourteen patients from 5 centers underwent a total of 71 procedures with an average follow-up of 54 months. Mean age at surgery was 6.8 years. Means of initial and final curves were 74 and 36 degrees, respectively (51% correction). Spine grew at an average of 39 mm (11.2 mm per year). Implant-related complications were the most common (8/14, 57%), including failure of proximal construct (5/14), rod breakage (2/14), and prominent implants (1/14). There was no significant difference between screws and hooks as proximal anchors (Fischer test). Two patients had deep infection that needed debridement.

Conclusions:
This retrospective pooled data study is the first report on the treatment of early-onset NF1 scoliosis with GRs. The use of GRs in these patients effectively controls the spinal deformity and facilitates growth of the spine. The complications were no greater than those seen in other conditions causing EOS. Failure of proximal anchors was found to be the most common complication.

Level of Evidence:
Level IV—retrospective case series.
CHOROIDAL BLOOD FLOW AND THICKNESS AS PREDICTORS FOR RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION
Authors: Okamoto Masahiro , Yamashita Mariko , Sakamoto Taiji , Ogata Nahoko 
Published: February 2017

Purpose:
To determine the choroidal blood flow and subfoveal choroidal thickness (SCT) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO).

Methods:
Thirty-two eyes of 32 patients with macular edema secondary to a BRVO were treated with a single intravitreal injection of ranibizumab (IVR) and were followed for 2 months. The central retinal thickness and SCT, and the retinal and choroidal blood flows were evaluated, and they were compared between the recurrent and resolved groups.

Results:
At the baseline, the SCT of eyes with a BRVO was significantly thicker than that of the fellow eye (P < 0.01). It was also significantly thicker in the recurrent group than in the resolved group (P = 0.03). The reduction of the retinal blood flow was found only after 1 week in the resolved group. The SCT and choroidal blood flow were significantly reduced during the follow-up period in the resolved group but not in the recurrent group.

Conclusion:
The choroid is involved in the pathology of BRVO and the SCT at the baseline may be a predictive factor in the treatment of intravitreal injection of ranibizumab for macular edema secondary to BRVO.