bluuebunny/crossref_metadata_2025_split huggingface dataset:
The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B′-LTR for driving gene expression
Authors: Qu Di , Li Chuan , Sang Feng , Li Qiang , Jiang Zhi-Qiang , Xu Li-Ran , Guo Hui-Jun , Zhang Chiyu , Wang Jian-Hua 
Published: October 2016

AbstractThe 5′ end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized. Here, by characterizing the sequences and functions of LTRs from endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core promoter and NF-κB element are associated with varied LTR capacity for driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B′-LTR for driving viral gene transcription upon stimulation is associated with an increased level of viral reactivation. Moreover, we demonstrated that the introduction of CRISPR/dead Cas9 targeting Sp1 or NF-κB element suppressed viral gene expression. Taken together, our study characterized LTRs from endemic HIV-1 subtypes in China and suggests a potential target for the suppression of viral gene expression and a novel strategy that facilitates the accomplishment of a functional cure.
Na+ compartmentalization related to salinity stress tolerance in upland cotton (Gossypium hirsutum) seedlings
Authors: Peng Zhen , He Shoupu , Sun Junling , Pan Zhaoe , Gong Wenfang , Lu Yanli , Du Xiongming 
Published: October 2016

AbstractThe capacity for ion compartmentalization among different tissues and cells is the key mechanism regulating salt tolerance in plants. In this study, we investigated the ion compartmentalization capacity of two upland cotton genotypes with different salt tolerances under salt shock at the tissue, cell and molecular levels. We found that the leaf glandular trichome could secrete more salt ions in the salt-tolerant genotype than in the sensitive genotype, demonstrating the excretion of ions from tissue may be a new mechanism to respond to short-term salt shock. Furthermore, an investigation of the ion distribution demonstrated that the ion content was significantly lower in critical tissues and cells of the salt-tolerant genotype, indicating the salt-tolerant genotype had a greater capacity for ion compartmentalization in the shoot. By comparing the membrane H+-ATPase activity and the expression of ion transportation-related genes, we found that the H+-ATPase activity and Na+/H+antiporter are the key factors determining the capacity for ion compartmentalization in leaves, which might further determine the salt tolerance of cotton. The novel function of the glandular trichome and the comparison of Na+compartmentalization between two cotton genotypes with contrasting salt tolerances provide a new understanding of the salt tolerance mechanism in cotton.
An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme
Authors: Liang Jianfeng , Meng Qinghua , Zhao Wanni , Tong Pan , Li Ping , Zhao Yuanli , Zhao Xiaodong , Li Hua 
Published: October 2016

AbstractProper regulation of neuronal gene expression is crucial for the development and differentiation of the central nervous system. The transcriptional repressor REST (repressor element-1 silencing transcription factor) is a key regulator in differentiation of pluripotent stem cells to neuronal progenitors and mature neurons. Dysregulated REST activity has been implicated in various diseases, among which the most deadly is glioblastoma multiforme (GBM). Here we have developed anexpression-basedRESTsignature (EXPREST), a device providing quantitative measurements of REST activity for GBM tumors. EXPREST robustly quantifies REST activity (REST score) using gene expression profiles in absence of clinic-pathologic assessments of REST. Molecular characterization of REST activity identified global alterations at the DNA, RNA, protein and microRNA levels, suggesting a widespread role of REST in GBM tumorigenesis. Although originally aimed to capture REST activity, REST score was found to be a prognostic factor for overall survival. Further, cell lines with enhanced REST activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. In contrast, cell lines with low REST score were more sensitive to cytotoxic drugs including Mitomycin, Camptothecin and Cisplatin. Together, our work suggests that therapeutic targeting of REST provides a promising opportunity for GBM treatment.
Elevation in fibroblast growth factor 23 and its value for identifying subclinical atherosclerosis in first-degree relatives of patients with diabetes
Authors: Hu Xiang , Ma Xiaojing , Luo Yuqi , Xu Yiting , Xiong Qin , Pan Xiaoping , Bao Yuqian , Jia Weiping 
Published: October 2016

AbstractAccumulating evidence supported an association between diabetes and fibroblast growth factor 23 (FGF23). The goal of the present study was to explore alteration in serum FGF23 levels and to assess its value for identifying subclinical atherosclerosis in normoglycemic individuals with a first-degree family history of diabetes (FHD). The study enrolled 312 subjects with a first-degree FHD and 1407 subjects without an FHD. Serum FGF23 levels were detected by a sandwich enzyme-linked immunosorbent assay. Serum FGF23 levels were much higher in subjects with a first-degree FHD than in those without an FHD (P = 0.006). A first-degree FHD was positively associated with serum FGF23 levels, independent of C-IMT and cardiovascular factors (both P < 0.05). In subjects with a first-degree FHD, only those with serum FGF23 levels in the upper quartile were more likely to have an increased C-IMT (odds ratio = 2.263, P < 0.05). As conclusions, a first-degree FHD contributes to the increased serum FGF23 levels independently. Subjects with a first-degree FHD need higher serum FGF23 levels to indicate subclinical atherosclerosis. The influence of a first-degree FHD on serum FGF23 levels should be considered to avoid overestimating the risk of cardiovascular disease in normoglycemic individuals with a first-degree FHD.
Effects of Biofeedback on Control and Generalization of Nasalization in Typical Speakers
Authors: Heller Murray Elizabeth S. , Mendoza Joseph O. , Gill Simone V. , Perkell Joseph S. , Stepp Cara E. 
Published: October 2016

Purpose

The purpose of this study was to determine the effects of biofeedback on control of nasalization in individuals with typical speech.

Method
Forty-eight individuals with typical speech attempted to increase and decrease vowel nasalization. During training, stimuli consisted of consonant-vowel-consonant (CVC) tokens with the center vowels /a/ or /i/ in either a nasal or nonnasal phonemic context (e.g., /mim/ vs. /bib/), depending on the participant’s training group. Half of the participants had access to augmentative visual feedback during training, which was based on a less-invasive acoustic, accelerometric measure of vowel nasalization—the Horii oral–nasal coupling (HONC) score. During pre- and posttraining assessments, acoustically based nasalance was also measured from the center vowels /a/, /i/, /æ/, and /u/ of CVCs in both nasal and nonnasal contexts.

Results
Linear regressions indicated that both phonemic contexts (nasal or nonnasal) and the presence of augmentative visual feedback during training were significant predictors for changes in nasalance scores from pre- to posttraining.

Conclusions
Participants were able to change the nasalization of their speech following a training period with HONC biofeedback. Future work is necessary to examine the effect of such training in individuals with velopharyngeal dysfunction.
Multiuser untrusted relay networks with joint cooperative jamming and opportunistic scheduling under perfect and outdated CSI
Authors: Ding Fan , Wang Hui , Zhang Shengli , Dai Mingjun 
Published: October 2016

A joint cooperative jamming and opportunistic scheduling (CJOS) scheme is proposed for a downlink multiuser relay network (MRN) with an untrusted fixed‐gain amplify‐and‐forward relay. Specifically, the source's confident message is protected by employing CJ at the destinations and multiuser diversity is harvested via OS. Unified tight approximation and asymptotic expressions for the system secrecy outage probability with perfect/outdated channel state information (CSI) are derived. Our results explicitly show that with perfect CSI, CJOS scheme can improve the secrecy diversity order from 1/2 in single‐user networks up to full diversity of 1 in MRNs. However, the outdated CSI degrades the secrecy diversity order from 1 to 1/2.
Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities
Authors: Subudhi Sumit K. , Aparicio Ana , Gao Jianjun , Zurita Amado J. , Araujo John C. , Logothetis Christopher J. , Tahir Salahaldin A. , Korivi Brinda R. , Slack Rebecca S. , Vence Luis , Emerson Ryan O. , Yusko Erik , Vignali Marissa , Robins Harlan S. , Sun Jingjing , Allison James P. , Sharma Padmanee 
Published: October 2016

Significance
Immune checkpoint therapies have garnered significant attention due to their ability to induce dramatic clinical responses in patients with various solid tumor malignancies, including prostate cancer. However, these therapeutic agents often elicit immune-related adverse events (irAEs) that may result in substantial morbidity. Early intervention can markedly reduce the severity of the irAEs, but biomarkers that allow for their early detection and guide their management are lacking. Based on peripheral blood samples collected longitudinally in two prostate cancer clinical trials, we propose CD8 T-cell clonal expansion within the systemic circulation as a potential correlative biomarker of immune-related adverse events that occur with ipilimumab therapy.
Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training
Authors: Bello-Medina Paola C. , Flores Gonzalo , Quirarte Gina L. , McGaugh James L. , Prado Alcalá Roberto A. 
Published: October 2016

Significance
Interference with activity of cerebral structures, including the dorsal striatum, produces amnesia after moderate levels of training; such interference, nonetheless, becomes ineffective when animals are subjected to intense training procedures. The mechanisms that mediate the protective effect of intense training are unknown. This report shows an increase in relative density of mushroom spines in medium spiny neurons (MSNs) of the dorsal striatum, which depends upon the intensity of training; relative density of mushroom spines in MSNs of nucleus accumbens, on the other hand, is augmented after noncontingent administration of a foot-shock alone. These findings suggest that increased mushroom spinogenesis produced by intense training strengthens memory consolidation and facilitates transfer of information from the dorsal striatum to other cerebral structures.
Efficient ECH-assisted plasma start-up using trapped particle configuration in the versatile experiment spherical torus
Authors: An YoungHwa , Lee Jeongwon , Jo JongGab , Jung Bong-Ki , Lee HyunYeong , Chung Kyoung-Jae , Na Yong-Su , Hahm T.S. , Hwang Y.S. 
Published: October 2016

Abstract
An efficient and robust ECH (electron cyclotron heating)-assisted plasma start-up scheme with a low loop voltage and low volt-second consumption utilizing the trapped particle configuration (TPC) has been developed in the versatile experiment spherical torus (VEST). The TPC is a mirror-like magnetic field configuration providing a vertical magnetic field in the same direction as the equilibrium field. It significantly enhances ECH pre-ionization with enhanced particle confinement due to its mirror effect, and intrinsically provides an equilibrium field with a stable decay index enabling prompt plasma current initiation. Consequently, the formation of TPC before the onset of the loop voltage allows the plasma to start up with a lower loop voltage and lower volt-second consumption as well as a wider operation range in terms of ECH pre-ionization power and H2 filling pressure. The TPC can improve the widely-used field null configuration significantly for more efficient start-up when ECH pre-ionization is used. This can then be utilized in superconducting tokamaks requiring a low loop voltage start-up, such as ITER, or in spherical tori with limited volt-seconds. The TPC can be particularly useful in superconducting tokamaks with a limited current slew-rate of superconducting PF coils, as it can save volt-second consumption before plasma current initiation by providing prompt initiation with an intrinsic stable equilibrium field.
Prognostic Value of Transient Elastography in Human Immunodeficiency Virus-Infected Patients With Chronic Hepatitis C
Authors: Pérez-Latorre Leire , Rivero-Juárez Antonio , Hontañón Víctor , Díez Cristina , Cuenca Francisca , Martín-Carbonero Maria Luz , Montes María L. , Bellón José M. , Aldámiz-Echevarría Teresa , Carrero Ana , Rivero Antonio , González-García Juan , Berenguer Juan 
Published: October 2016

AbstractBackgroundOur objective was to study the prognostic value of liver stiffness (LS) in HIV-infected patients with chronic hepatitis C (CHC).MethodsWe analyzed HIV-infected patients with compensated CHC and at least 1 determination of LS. The primary outcome was the occurrence of liver-related events (LRE), namely, decompensation or hepatocellular carcinoma, whichever occurred first. We selected patients without sustained viral response (SVR) or end-of-treatment response (ETR) during follow-up and allocated them to an estimation cohort (EC) and a validation cohort (VC).ResultsThe study population comprised 1292 patients. After a median follow-up of 5.8 years, 90 patients experienced LRE and 73 died. In the subgroup of 957 patients without SVR or ETR, the area under the receiver operating characteristic curves (AUROCs) (95% confidence interval [CI]) of LS for prediction of LRE in the EC (n = 634) and the VC (n = 323) were 0.87 and 0.88, respectively. The best cutoff value of LS to rule out LRE in the EC was 12 kPa, with a negative predictive value of 98.3% in the EC and 98.2% in the VC. Per each 1 kPa and 5 kPa increase above 12 kPa, the hazard ratio of LRE (taking into account death as a competing risk) was 1.07 (95% CI, 1.05–1.08) and 1.38 (95% CI, 1.31–1.46), respectively.ConclusionsLiver stiffness is very accurate for predicting LRE in coinfected patients. Patients with an LS &lt;12 kPa had a 98% probability of not developing LRE after a median follow-up of almost 6 years. Above the 12-kPa cutoff, the hazard of LRE increases proportionally with LS.
Correlations of In Vitro Assays for Assessing Cytotoxicity and Biocompatibility of Contact Lens Multipurpose Solutions
Authors: Huang Ling C. , Salvador-Silva Mercedes , Leang Ronika S. 
Published: October 2016

Objectives:
To demonstrate correlations among in vitro assays used for assessing cytotoxicity of contact lens multipurpose solution (MPS) and propose the use of multiple assays as a part of preclinical evaluation for MPS biocompatibility assessment.

Methods:
The effect of four different MPS on cell cytotoxicity, metabolic activity, and membrane integrity was performed by evaluating toxicity, expression of tight junction protein zonula occludens-1, and transepithelial electrical resistance in human corneal epithelial cells and Chinese hamster fibroblast cells.

Results:
Cytotoxicity of four MPS was assayed with five different experimental systems at various concentrations. In vitro MPS-induced cytotoxicity was dependent on assay choice, concentration of MPS used, and duration of treatment. Overall, MPS-1 and MPS-2 were comparable to MPS-4 and better than MPS-3 in maintaining corneal barrier integrity and cell viability.

Conclusions:
In vitro cytotoxicity testing with MPS exposure to monolayer of cells in culture could be used as a tool to understand the potential cytotoxicity profiles of MPS and possibly a predictor of clinical outcome. Furthermore, MPS effects on in vitro cytotoxicity are best demonstrated by performing multiple assays to evaluate cell viability, metabolic activity, and membrane integrity during development.
Are Women Who Exit Colposcopy Without Treatment at Elevated Risk for Cervical Cancer?
Authors: Koné Péfoyo Anna J. , Wang Li , Gao Julia , Kupets Rachel 
Published: October 2016

Objective
This study aims to estimate the risk of cervical cancer and impact of treatment and other factors in women referred for high-grade (HG) and low-grade (LG) cytologic changes and discharged from colposcopy.

Materials and Methods
A retrospective cohort study identified 14,787 and 41,916 women with a first-time HG and LG cytologic abnormality between 2007 and 2010 and underwent colposcopy within 1 year. Treatment status was determined within the episode of care. Incidence of cervical cancer postcolposcopy was determined up to March 2015. Logistic regression assessed impact of colposcopic care and patient factors on cancer risk.

Results
A total of 62% HG and 28.5% LG had treatment. A total of 28% and 37% with HG and LG abnormalities had only 1 colposcopic evaluation. Subsequent cancer incidence in the untreated HG group was 1.1% versus 0.3% in the treated group. For the LG group, cancer rates were 0.08% in both treatment groups. In the HG group, those with initial colposcopy only and no treatment had an elevated risk [adjusted odds ratio = 6.6 (95% CI = 3.9–11)] compared with treatment with multiple follow-ups. Other significant factors were advancing age and no screening postcolposcopy. For the LG group, those with initial colposcopy only were more at risk regardless of treatment [adjusted odds ratio = 3.8 (95% CI = 1.8–8.1)] compared with multiple colposcopies.

Conclusions
Women who are untreated, with index HG cytology, remain at elevated risk for cervical cancer when the colposcopic episode is limited to 1 examination. Centralized programs are required to ensure that such women are not discharged prematurely or lost to follow up from colposcopy and subsequent screening.
Outcome Comparison in Children Undergoing Extracorporeal Life Support Initiated at a Local Hospital by a Mobile Cardiorespiratory Assistance Unit or at a Referral Center*
Authors: d’Aranda Erwan , Pastene Bruno , Ughetto Fabrice , Cotte Jean , Esnault Pierre , Fouilloux Virginie , Mazzeo Cécilia , Mancini Julien , Lebel Stéphane , Paut Olivier 
Published: October 2016

Purpose:To compare characteristics and outcome in children undergoing extracorporeal life support initiated in an extracorporeal life support center or at the patient’s bedside in a local hospital, by means of a mobile cardiorespiratory assistance unit.Methods:A retrospective study in a single PICU during 6 years. Extracorporeal life support was started either in our center (control group) or in the local hospital (mobile cardiorespiratory assistance unit group). The data collected were demographics, markers of patient’s preextracorporeal life support condition, and outcome.Results:One hundred twenty-six children underwent extracorporeal life support, 105 in the control group and 21 in the mobile cardiorespiratory assistance unit group. There was no difference between groups in terms of age, weight, or Pediatric Risk of Mortality II score. There was a significant difference in organ failure etiology between groups, with more respiratory cases in the mobile cardiorespiratory assistance unit group (76.2%) and more cardiac surgery cases in the control group (60%;p< 0.001). The duration of extracorporeal life support was longer in the mobile cardiorespiratory assistance unit group than in the control group (10 [1–36] vs 5 [0–33] d;p= 0.003). PICU length of stay and mortality (60% vs 47.6%;p= 0.294) were not significantly different between the two groups. To allow comparison of a more homogenous population, a subgroup analysis was performed including only respiratory failure patients from the two groups (R-control group [n= 22] and R-mobile cardiorespiratory assistance unit group [n= 16]). PICU length of stay was 17 (3–64) days in the R-control group and 23 (1–45) days in the R-mobile cardiorespiratory assistance unit group (p= 0.564), and PICU mortality rate was 54.5% in the R-control group and 43.8% in the R-mobile cardiorespiratory assistance unit group (p= 0.511). There was no difference between the R-groups for age, weight, Pediatric Risk of Mortality II score, and markers of kidney or liver dysfunction, and lactate blood levels.Conclusion:Extracorporeal life support can be safely initiated at children’s bedside in the local hospital and then transported to the specialized referral center. Our results support the validity of an interregional organization of mobile cardiorespiratory assistance unit teams.
Making Improvements in the ED
Authors: Benner Christopher A. , Mora Erika , Mueller Emily , Seagull F. Jacob , Walkovich Kelly , Johnson Kaleena , Halverson Schuyler , Rothman Ed , Hucks George , Younger John G. , Nypaver Michele M. 
Published: October 2016

Objectives
Febrile neutropenic pediatric patients are at heightened risk for serious bacterial infections, and rapid antibiotic administration (in <60 minutes) improves survival. Our objectives were to reduce the time-to-antibiotic (TTA) administration and to evaluate the effect of overall emergency department (ED) busyness on TTA.

Methods
This study was a quality improvement initiative with retrospective chart review to reduce TTA in febrile children with underlying diagnosis of cancer or hematologic immunodeficiency who visited the pediatric ED. A multidisciplinary clinical practice guideline (CPG) was implemented to improve TTA. The CPG's main focus was delivery of antibiotics before availability of laboratory data. We collected data on TTA during baseline and intervention periods. Concurrent patient arrivals to the ED per hour served as a proxy of busyness. Time to antibiotic was compared with the number of concurrent arrivals per hour. Analyses included scatter plot and regression analysis.

Results
There were 253 visits from October 1, 2010 to March 30, 2012. Median TTA administration dropped from 207 to 89 minutes (P < 0.001). Eight months after completing all intervention periods, the median had dropped again to 44 minutes with 70% of patients receiving antibiotics within 60 minutes of ED arrival. There was no correlation between concurrent patient arrivals and TTA administration during the historical or intervention periods.

Conclusions
Implementation of a CPG and process improvements significantly reduced median TTA administration. Total patient arrivals per hour as a proxy of ED crowding did not affect TTA administration. Our data suggest that positive improvements in clinical care can be successful despite fluctuations in ED patient volume.