bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA vaccine ROP29 from Toxoplasma gondii containing R848 enhances protective immunity in mice
Authors: Lu Gang , Zhou Jian , Zhao Ying hui , Wang Lin 
Published: August 2018

SummaryAimsToxoplasma gondii is an intracellular parasite that causes a global epidemic parasitic disease. Studies using DNA vaccines for the control of toxoplasmosis have made considerable progress. ROP proteins were proven to be excellent candidates for T. gondii DNA vaccine development.Methods and ResultsHere, a ROP29 DNA vaccine was successfully produced and injected into mice in combination with R848 to evaluate its ability to provide protection against T. gondii challenge. Compared with other mice, the mice injected with R848/pROP29 produced higher levels of IgG, IgG2a, interleukin (IL)‐12, and interferon gamma (IFN‐γ). Moreover, after a challenge of 20 T. gondii cysts, the number of brain cysts was lower in the R848/pROP29‐immunized mice than in the other experimental mice.ConclusionsR848 could improve the productions of IL‐12 and IFN‐γ, thus enhancing the immune responses stimulated by the pROP29 DNA vaccine.
Transient
Behavior of Three-Fluid Cross-Flow Heat Exchanger Under the Influence of Temperature
Nonuniformity
Authors: Aasi Harpreet
Kaur , Mishra Manish 
Published: August 2018

Abstract
A typical three-fluid cross-flow heat exchanger with nonuniform inlet temperature in the central (hot) fluid is considered for the present analysis. Steady and transient state behavior of the heat exchanger is observed for four different temperature nonuniformity models along with step excitation in inlet temperature of the central fluid. Longitudinal heat conduction in the separating walls and the effect of fluid back-mixing along with axial dispersion effect are considered within the fluids with constant thermophysical fluid properties. The solution of governing equations has been obtained using implicit finite difference scheme. Temperature distribution over the separating walls has been depicted providing a clear view of the thermal stresses generated in separating walls. The performance for all the four cross-flow arrangements has been analyzed by comparing that with and without nonuniform conditions. It is found that the nonuniformity in inlet temperature has an adverse effect on the performance of heat exchanger.
Evaluation of ADA HbA1c criteria in the diagnosis of pre-diabetes and diabetes in a population of Chinese adolescents and young adults at high risk for diabetes: a cross-sectional study
Authors: Li Ge , Han Lanwen , Wang Yonghui , Zhao Yanglu , Li Yu , Fu Junling , Li Ming , Gao Shan , Willi Steven M 
Published: August 2018

ObjectiveWe aimed to assess haemoglobin A1c (HbA1c) for the diagnosis of pre-diabetes and diabetes in a population of Chinese youths at risk of metabolic syndrome.SettingBeijing, China.ParticipantsA total of 581 subjects aged 14–28 years underwent evaluation including an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell function and a number of cardiovascular disease risk factors were evaluated. Receiver operating characteristic (ROC) curves were used to assess the screening efficacy of HbA1c.ResultsUsing OGTT data as a standard, the majority (70.0%, 7/10) of subjects with diabetes would have been diagnosed with HbA1c ≥6.5%. In contrast, only 28.1% (16/57) of subjects with pre-diabetes possessed elevated HbA1cs, while the majority (68.4%) had normal HbA1cs. On the contrary, a total of 8.1% (39/479) of youths in the normal HbA1c category (<5.7%) and 21.3% in the pre-diabetes category had pre-diabetes. In the ROC analysis, the area under the curve (AUC) for HbA1c identifying pre-diabetes was 0.680(95% CI 0.640 to 0.719); the optimal threshold was 5.5%, with a sensitivity of 61.4% and specificity of 68.5%. For type 2 diabetes mellitus, the AUC for HbA1c was 0.970 (0.952 to 0.982), and the optimal threshold was 6.1%, with a sensitivity of 90.0% and a specificity of 98.7%. Applying these new cut-offs, pre-diabetic participants (HbA1c 5.5%–6.1%) had lower disposition index and higher risk of dyslipidaemia (OR=1.61,95% CI 1.10 to 2.37) and metabolic syndrome (OR=2.09, 1.27 to 3.45) than those with normal HbA1c (<5.5%).ConclusionThe American Diabetes Association’s established HbA1c criteria for pre-diabetes and diabetes (5.7% and 6.5%) may not be appropriately applied to adolescents and young adults in China. Our findings suggest that those with HbA1c of 5.5%–6.1% already exhibit impaired β-cell function and increased cardiometabolic risk factors which may warrant intervention.Trial registration numberNCT03421444.
Sex differences in 90-day outcomes after mechanical thrombectomy for acute ischemic stroke
Authors: Madsen Tracy E , DeCroce-Movson Eliza , Hemendinger Morgan , McTaggart Ryan A , Yaghi Shadi , Cutting Shawna , Furie Karen L , Saad Ali , Siket Matthew S , Jayaraman Mahesh V 
Published: August 2018

BackgroundIt is largely unknown whether functional outcomes after mechanical thrombectomy for large vessel occlusion (LVO) ischemic strokes differ by sex in non-clinical trial populations. We investigated sex differences in 90-day outcomes among ischemic stroke patients receiving mechanical thrombectomy.MethodsThis was a prospective cohort of adults treated with mechanical thrombectomy for LVO at a single academic comprehensive stroke center from July 2015 to April 2017. Data on independence (mRS ≤2) at hospital discharge and 90 days were collected prospectively. Multiple logistic regression was used to determine the association between sex and 90-day independence, first adjusting for demographics, pre-stroke mRS, and NIHSS, then by co-morbidities and time to thrombectomy, and finally by vessel recanalization and use of intravenous thrombolysis.ResultsWe included 279 patients, 52% of whom were female. Compared with males, females were older (median years (IQR) 81 (75–88) vs. 71.5 (60–81), P<0.001) and had higher baseline NIHSS (mean SD 18.2±7.5 vs . 16.0±7.1, P=0.02). Similar proportions of males and females had pre-stroke mRS ≤2 (73.3% vs.67.1%, P=0.27). In multivariate analyses, males and females had a similar likelihood of being independent at discharge (aOR 0.71 (95%CI 0.32 to 1.58)), but females were less likely to be independent at 90 days (aOR 0.37 95% CI 0.16 to 0.87).ConclusionsIn patients treated with mechanical thrombectomy for LVOs at a large comprehensive stroke center, females were less likely to be independent at 90 days. Future research should investigate contributors to poor outcomes post-discharge in females with LVOs, along with potential interventions to improve outcomes.
Child-adult differences in neuromuscular fatigue are muscle dependent
Authors: Piponnier Enzo , Martin Vincent , Bontemps Bastien , Chalchat Emeric , Julian Valérie , Bocock Olivia , Duclos Martine , Ratel Sébastien 
Published: August 2018

The aim of the present study was to compare the development and etiology of neuromuscular fatigue of the knee extensor (KE) and plantar flexor (PF) muscles during repeated maximal voluntary isometric contractions (MVICs) between children and adults. Prepubertal boys ( n = 21; 9–11 yr) and men ( n = 24; 18–30 yr) performed two fatigue protocols consisting of a repetition of 5-s isometric MVIC of the KE or PF muscles interspersed with 5-s passive recovery periods until MVIC reached 60% of its initial value. The etiology of neuromuscular fatigue of the KE and PF muscles was investigated by means of noninvasive methods, such as the surface electromyography, single and doublet magnetic stimulation, twitch interpolation technique, and near-infrared spectroscopy. The number of repetitions performed was significantly lower in men (15.4 ± 3.8) than boys (38.7 ± 18.8) for the KE fatigue test. In contrast, no significant difference was found for the PF muscles between boys and men (12.1 ± 4.9 and 13.8 ± 4.9 repetitions, respectively). Boys displayed a lower reduction in potentiated twitch torque, low-frequency fatigue, and muscle oxygenation than men whatever the muscle group considered. In contrast, voluntary activation level and normalized electromyography data decreased to a greater extent in boys than men for both muscle groups. To conclude, boys experienced less peripheral and more central fatigue during repeated MVICs than men whatever the muscle group considered. However, child-adult differences in neuromuscular fatigue were muscle-dependent since boys fatigued similarly to men with the PF muscles and to a lower extent with the KE muscles. NEW & NOTEWORTHY Child-adult differences in neuromuscular fatigue during repeated maximal voluntary contractions are specific to the muscle group since children fatigue similarly to adults with the plantar flexor muscles and to a lower extent with the knee extensor muscles. Children experience less peripheral fatigue and more central fatigue than adults, regardless of the muscle group considered.
Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis
Authors: Oristian Kristianne M. , Crose Lisa E.S. , Kuprasertkul Nina , Bentley Rex C. , Lin Yi-Tzu , Williams Nerissa , Kirsch David G. , Linardic Corinne M. 
Published: August 2018

Abstract
A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3–FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3–FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and sustain tumor growth. Previously, we showed that PAX3–FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as demonstrated by increased YAP1 expression and decreased MST activity. We hypothesized that ablating MST/Hippo signaling in a genetically engineered mouse model (GEMM) of aRMS would accelerate tumorigenesis. To this end, MST1/2-floxed (Stk3F/F;Stk4F/F) mice were crossed with a previously established aRMS GEMM driven by conditional expression of Pax3:Foxo1 from the endogenous Pax3 locus and conditional loss of Cdkn2a in Myf6 (myogenic factor 6)-expressing cells. Compared with Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ controls, Stk3F/F;Stk4F/F;Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ animals displayed accelerated tumorigenesis (P &lt; 0.0001) and increased tumor penetrance (88% vs. 27%). GEMM tumors were histologically consistent with aRMS. GEMM tumor-derived cell lines showed increased proliferation and invasion and decreased senescence and myogenic differentiation. These data suggest that loss of MST/Hippo signaling acts with Pax3:Foxo1 expression and Cdkn2a loss to promote tumorigenesis. The rapid onset and increased penetrance of tumorigenesis in this model provide a powerful tool for interrogating aRMS biology and screening novel therapeutics.
Significance: A novel mouse model sheds light on the critical role of Hippo/MST downregulation in PAX3-FOXO1–positive rhabdomyosarcoma tumorigenesis. Cancer Res; 78(19); 5513–20. ©2018 AACR.
Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss
Authors: Murali Bhavna , Ren Qihao , Luo Xianmin , Faget Douglas V. , Wang Chun , Johnson Radia Marie , Gruosso Tina , Flanagan Kevin C. , Fu Yujie , Leahy Kathleen , Alspach Elise , Su Xinming , Ross Michael H. , Burnette Barry , Weilbaecher Katherine N. , Park Morag , Mbalaviele Gabriel , Monahan Joseph B. , Stewart Sheila A. 
Published: August 2018

Abstract
The role of the stromal compartment in tumor progression is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition of p38MAPKα could reduce breast cancer metastases in a clinically relevant model. Orally administered, small-molecule inhibitors of p38MAPKα or its downstream kinase MK2 each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. This effect was primarily mediated by inhibition of the p38MAPKα pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, these inhibitors reduced tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity that drastically affects quality of life for patients with cancer. These data underscore the vital role played by stromal-derived factors in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss.
Significance: Pharmacologically targeting the stromal p38MAPK-MK2 pathway limits metastatic breast cancer growth, preserves bone quality, and extends survival. Cancer Res; 78(19); 5618–30. ©2018 AACR.
Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder Cancer Treated with Durvalumab
Authors: Raja Rajiv , Kuziora Michael , Brohawn Philip Z. , Higgs Brandon W. , Gupta Ashok , Dennis Phillip A. , Ranade Koustubh 
Published: August 2018

Abstract

Purpose:
Immunotherapy has transformed the treatment of many solid tumors, with some patients deriving long-term benefit, but how to identify such patients remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from plasma can be an indicator of disease progression, response to therapy, and clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a valuable noninvasive and tumor-specific marker for longitudinal monitoring of tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an anti-PD-L1 therapy.

Experimental Design:
Variant allele frequencies (VAF) of somatic mutations in 73 genes were assessed in ctDNA using targeted sequencing in a discovery cohort consisting of 28 patients with non–small cell lung cancer (NSCLC) and two validation NSCLC and urothelial cancer (UC) cohorts of 72 and 29 patients, respectively, to correlate ctDNA changes with clinical outcomes.

Results:
Somatic variants were detected in 96% of patients. Changes in VAF preceded radiographic responses, and patients with reduction in VAF at 6 weeks had significantly greater reduction in tumor volume, with longer progression-free and overall survival.

Conclusions:
ctDNA VAF changes are strongly correlated with duration of treatment, antitumor activity, and clinical outcomes in NSCLC and UC. Early on-treatment reduction in ctDNA VAF may be a useful predictor of long-term benefit from immunotherapy. Prospective studies should validate these findings and the value of utilizing early changes in ctDNA for therapeutic decision making by identifying nonresponders to checkpoint inhibitor monotherapies and guiding combination therapies.
A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats
Authors: Dorotea Debra , Kwon Guideock , Lee Jung Hwa , Saunders Erika , Bae Yun Soo , Moon Sung Hwan , Lee Soo Jin , Cha Dae Ryong , Ha Hunjoo 
Published: August 2018

<b><i>Background:</i></b> NADPH oxidases (Nox) is a major enzyme system contributing to oxidative stress, which plays an important role in the pathogenesis of diabetic kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in mice. As the standard diabetic mice cannot fully mimic human DKD, the present study was aimed to show the dose-dependent effect and to provide a confirmatory evidence of APX-115 in attenuating DKD in diabetic rats. <b><i>Method:</i></b> Type 1 diabetes was induced by a single 60 mg/kg intraperitoneal injection of streptozotocin in Sprague-Dawley rats. 0.5, 5, or 30 mg APX-115/kg/day or losartan 1 mg/kg/day were administered orally to diabetic rats for 8 weeks. <b><i>Results:</i></b> APX-115 treatment showed an improvement in kidney function and tubular and podocyte ­injury, as well as attenuation of inflammation, fibrosis, and oxidative stress as much as losartan, a comparative drug and mainstay treatment in DKD. Therapeutic effect of APX-115 was exhibited in a dose-dependent manner; a dose of 30 mg/kg displayed a superior efficacy. <b><i>Conclusion:</i></b> This finding verified the pre-clinical data of APX-115 in protecting against DKD, which is important to bring APX-115 toward the next stage of drug development.
U-Pb dating, Lu-Hf isotope systematics and chemistry of zircon from the Morro do Polvilho meta-trachydacite: constraints on sources of magmatism and on the depositional age of the São Roque Group
Authors: Henrique-Pinto Renato , Janasi Valdecir De Assis , Campanha Ginaldo Ademar da Cruz 
Published: August 2018

We present new in situ geochronological data of controversial silicic metavolcanic rocks from the lower terrigenous-metavolcanic sequence of the São Roque Group, Ribeira Belt, confirming that they are older than the rocks of higher-metamorphic grade sequences of the Serra do Itaberaba Group. The age of the Polvilho meta-trachydacite was established at 1760 ± 17 Ma, furthermore the results suggest that the bi-modal volcanism of the Boturuna Formation has parent melts from an old (Archean to Paleoproterozoic) continental crust that was melted in a within-plate environment. Trace-element chemistry of zircon, suggests similarities with high-temperature melts (T Zrsat = 900–915ºC) similar to A-type granites (high negative EuN/EuN* and moderate positive CeN/CeN*) from continental sources under reducing conditions.
Significant Geographies
Authors: Laachir Karima , Marzagora Sara , Orsini Francesca 
Published: August 2018

Abstract
One of the problems with current theories of world literature is that the term “world” is insufficiently probed and theorized. As a category, “world” is too generic and suggests a continuity and seamlessness that are both deceptive and self-fulfilling. Easy invocations of “world” and “global” (novel, literary marketplace) replicate the blindspots that Sanjay Krishnan identified when he called the global an instituted perspective, with macro-theories drawing unproblematically on theories of globalization elaborated in the social sciences. Instead, in our comparative project Multilingual Locals and Significant Geographies we argue that to theorize world literature taking on board the complexities, layers and multiplicity of “literatures in the world” (as S. Shankar prefers to call it), we need a richer spatial imagination of the “world.” Here we propose the notion of “significant geographies” as the conceptual, imaginative, and real geographies that texts, authors, and language communities inhabit, produce, and reach out to.
Comparison of Clinical Presentation and Surgical Outcomes Between Recurrent Acute Rhinosinusitis and Chronic Rhinosinusitis
Authors: Sohn Hyun Gi , Park Seung Jin , Ryu In Sun , Lim Hyun Woo , Song Yong Jin , Yeo Nam-Kyung 
Published: August 2018

Introduction: The authors assessed clinical presentations and anatomic variants among patients with recurrent acute rhinosinusitis (RARS), chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). Additionally, differences in the postoperative improvement of each category were evaluated. Methods: The authors performed an analysis of 304 patients who underwent endoscopic sinus surgery. They were divided into groups with RARS, CRSsNP, and CRSwNP. Patients had to complete the Sino-Nasal Outcome Test (SNOT-20) on surgery 1 day before and 6 months after surgery. Patient demographics and comorbidities were reviewed. We reviewed all patients’ computed tomographic findings to analyze anatomic variants. Results: No significant differences were found among the average preoperative SNOT-20 scores of the 3 groups. Patients with RARS were significantly more likely to show agger nasi cells, Haller cells, and septal deviation on computed tomography. Those with CRSwNP had significantly smaller mean infundibular widths. All groups showed significantly improved SNOT-20 scores postoperatively. Conclusion: The different anatomic variants found among patients with RARS, CRSsNP, and CRSwNP can facilitate surgical prognostic evaluation.
Quantification of urinary sodium concentrations in term infants
Authors: Cullis Paul S , Cull Frith , Bruce Gordon , Johnston Allan , Patel Hetal , Jackson Lesley , Galloway Peter , Walker Gregor 
Published: August 2018

Background Infants with gastrointestinal conditions and poor weight gain are administered sodium supplementation based on urinary sodium concentrations. However, the reference range of urinary electrolytes is unknown. The aim of this study was to ascertain the normal values of urinary electrolytes in healthy, term infants. Secondary aims were to establish the relationship between urinary electrolytes with weight velocity and feeding practices. Methods Healthy, term (≥37 weeks’ gestation) infants were recruited. Parental questionnaires were completed before discharge and at six weeks. Electrolytes were quantified from a urine sample at six weeks. t-Tests and Mann-Whitney U tests were conducted for parametric and non-parametric electrolytes, respectively. Results A total of 200 infants were recruited before discharge. Twenty-nine follow-up questionnaires and urine samples were returned (nine female; mean gestational age 39 + 6 weeks [SD 9.9 days]; mean birthweight 3350 g [SD 483 g]; 17 breastfed, nine formula and three mixed; mean change in Z score for weight –0.914 [SD 0.814]). Majority (25/29) of infants had urinary sodium <20 mmo/L. Change in Z score for weight was similar between infants with sodium <20 mmol/L and >20 mmol/L ( P = 0.78). All exclusively breastfed infants had sodium <20 mmol/L, however, not statistically dissimilar to formula-fed infants ( P = 0.27). Conclusion Most term infants in this study had urinary sodium values <20 mmol/L with no identified relationship to weight velocity. Lower concentrations of sodium could be not quantified reliably because of the limitations of the analytical method that were used. More evidence is required to identify candidates for sodium supplementation.