bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance
Authors: Nooij Linda S. , ter Haar Natalja T. , Ruano Dina , Rakislova Natalia , van Wezel Tom , Smit Vincent T.H.B.M. , Trimbos Baptist J.B.M.Z. , Ordi Jaume , van Poelgeest Mariette I.E. , Bosse Tjalling 
Published: September 2017

Abstract
Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers.
Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort).
Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower (P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV+, HPV−/p53wt, HPV−/p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV+, 16.3% for HPV−/p53wt and 22.6% for HPV−/p53abn tumors (P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis (P = 0.020).
Conclusions: HPV− and HPV+ vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV−/p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV+ VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781–9. ©2017 AACR.
Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis
Authors: Ikonomidis Ignatios , Papadavid Evangelia , Makavos George , Andreadou Ioanna , Varoudi Maria , Gravanis Kostas , Theodoropoulos Kostas , Pavlidis George , Triantafyllidi Helen , Moutsatsou Paraskevi , Panagiotou Christina , Parissis John , Iliodromitis Efstathios , Lekakis John , Rigopoulos Dimitrios 
Published: September 2017

Background—
Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis.

Methods and Results—

One hundred fifty psoriasis patients were randomized to receive an anti–IL-12/23 (ustekinumab, n=50), anti–tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: −17.7% versus −19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (
P
<0.05). Compared with anti–TNF-α and cyclosporine, anti–IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (−25% versus −4% versus −2%), malondialdehyde (−27% versus +5% versus +26%), and NT-proBNP(−26% versus −13.6% versus 9.1%) and increase of fetuin-a (
P
<0.01). Pulse wave velocity and augmentation index were improved only after anti–IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting–untwisting (
P
<0.05).

Conclusions—
In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02144857.
Acute In Vivo Analysis of ATP Release in Rat Kidneys in Response to Changes of Renal Perfusion Pressure
Authors: Palygin Oleg , Evans Louise C. , Cowley Allen W. , Staruschenko Alexander 
Published: September 2017

Background

ATP and derivatives are recognized to be essential agents of paracrine signaling. It was reported that
ATP
is an important regulator of the pressure‐natriuresis mechanism. Information on the sources of
ATP
, the mechanisms of its release, and its relationship to blood pressure has been limited by the inability to precisely measure dynamic changes in intrarenal
ATP
levels in vivo.

Methods and Results

Newly developed amperometric biosensors were used to assess alterations in cortical
ATP
concentrations in response to changes in renal perfusion pressure (
RPP
) in anesthetized Sprague–Dawley rats.
RPP
was monitored via the carotid artery; ligations around the celiac/superior mesenteric arteries and the distal aorta were used for manipulation of
RPP
. Biosensors were acutely implanted in the renal cortex for assessment of
ATP
. Rise of
RPP
activated diuresis/natriuresis processes, which were associated with elevated
ATP
. The increases in cortical
ATP
concentrations were in the physiological range (1–3 μmol/L) and would be capable of activating most of the purinergic receptors. There was a linear correlation with every 1‐mm Hg rise in
RPP
resulting in a 70‐nmol/L increase in
ATP
. Furthermore, this elevation of
RPP
was accompanied by a 2.5‐fold increase in urinary H
2
O
2
.

Conclusions

Changes in
RPP
directly correlate with renal sodium excretion and the elevation of cortical
ATP
. Given the known effects of
ATP
on regulation of glomerular filtration and tubular transport, the data support a role for
ATP
release in the rapid natriuretic responses to acute increases in
RPP
.
Driving Performance After Self-Regulated Control Transitions in Highly Automated Vehicles
Authors: Eriksson Alexander , Stanton Neville A. 
Published: September 2017

Objective: This study aims to explore whether driver-paced, noncritical transitions of control may counteract some of the aftereffects observed in the contemporary literature, resulting in higher levels of vehicle control. Background: Research into control transitions in highly automated driving has focused on urgent scenarios where drivers are given a relatively short time span to respond to a request to resume manual control, resulting in seemingly scrambled control when manual control is resumed. Method: Twenty-six drivers drove two scenarios with an automated driving feature activated. Drivers were asked to read a newspaper or monitor the system and relinquish or resume control from the automation when prompted by vehicle systems. Driving performance in terms of lane positioning and steering behavior was assessed for 20 seconds post resuming control to capture the resulting level of control. Results: It was found that lane positioning was virtually unaffected for the duration of the 20-second time span in both automated conditions compared to the manual baseline when drivers resumed manual control; however, significant increases in the standard deviation of steering input were found for both automated conditions compared to baseline. No significant differences were found between the two automated conditions. Conclusion: The results indicate that when drivers self-paced the transfer back to manual control they exhibit less of the detrimental effects observed in system-paced conditions. Application: It was shown that self-paced transitions could reduce the risk of accidents near the edge of the operational design domain. Vehicle manufacturers must consider these benefits when designing contemporary systems.
Apparent diffusion coefficient (ADC) does not correlate with different serological parameters in myositis and myopathy
Authors: Meyer Hans-Jonas , Ziemann Oliver , Kornhuber Malte , Emmer Alexander , Quäschling Ulf , Schob Stefan , Surov Alexey 
Published: September 2017

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm2. In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10–3 mm2/s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10–3 mm2/s, respectively. The mean ADC values (1.15 ± 0.37 × 10–3 mm2/s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.
In Vitro Chondrotoxicity of Nonsteroidal Anti-inflammatory Drugs and Opioid Medications
Authors: Abrams Geoffrey D. , Chang Wenteh , Dragoo Jason L. 
Published: September 2017

Background:A variety of medications are administered to the intra-articular space for the relief of joint pain. While amide-type local anesthetics have been extensively studied, there is minimal information regarding the potential chondrotoxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid medications.Purpose:To investigate the in vitro chondrotoxicity of single-dose equivalent concentrations of ketorolac, morphine, meperidine, and fentanyl on human chondrocytes.Study Design:Controlled laboratory study.Methods:Human cartilage was arthroscopically harvested from the intercondylar notch and expanded in vitro. Gene expression of cultured chondrocytes before treatment was performed with quantitative polymerase chain reaction for type I collagen, type II collagen, aggrecan, and SOX9. Chondrocytes were then exposed to 0.01%, 0.02%, and 0.04% morphine sulfate; 0.3% and 0.6% ketorolac tromethamine; 0.5%, 1.0%, and 1.5% meperidine hydrochloride; 0.0005% and 0.001% fentanyl citrate; and saline. A custom bioreactor was used to constantly deliver medications, with the dosage of each medication and the duration of exposure based on standard dose equivalents, medication half-lives, and differences in the surface area between the 6-well plates and the native joint surface. After treatment, a live/dead assay was used to assess chondrocyte viability and if minimal cell death was detected. A subset of samples after treatment was maintained to analyze for possible delayed cell death.Results:All tested concentrations of ketorolac and meperidine caused significantly increased cell death versus the saline control, demonstrating a dose-response relationship. The morphine and fentanyl groups did not show increased chondrotoxicity compared with the saline group, even after 2 weeks of additional culture.Conclusion:In vitro exposure of chondrocytes to single-dose equivalent concentrations of either ketorolac or meperidine demonstrated significant chondrotoxicity, while exposure to morphine or fentanyl did not lead to increased cell death.
An Evaluation of the Effectiveness of the National Aeronautics and Space Administration Mission-X Child Health Promotion Program in the United States
Authors: Min Jungwon , Tan Zhengqi , Abadie Laurie , Townsend Scott , Xue Hong , Wang Youfa 
Published: September 2017

Purpose: To examine the effects of the National Aeronautics and Space Administration Mission-X: Train Like an Astronaut program (MX) on children’s health-related knowledge and behaviors of a sample of US participants. Design: A nonexperimental pilot intervention study in 5 cities with a pre–post comparison of children’s health-related knowledge and behaviors in the United States in 2014 and 2015. Sample: Children (n = 409) with a mean age (standard deviation) of 10.1 (1.7) years. Measures: Children answered pre- and postintervention questionnaires. We measured the differences in children’s health knowledge on nutrition and physical fitness and behaviors on diet and physical activity as scores. Intervention: A 6-week web- and school-based intervention for a healthier lifestyle by introducing physical fitness and science activities based on actual astronaut training under a teacher’s supervision. Analysis: Nonparametric analysis and logistic regression models. Results: Participants significantly improved both of their health behaviors on physical activity ( P < .001) and diet ( P = .06) and their health knowledge regarding nutrition ( P < .001) and physical fitness ( P < .001) after the intervention. The improvement in children’s behaviors ( P < .001), knowledge ( P < .001), and the total score ( P < .001) after intervention did not significantly vary by sex or age, after adjusting for year of participation and state of residency. Discussion: The MX seems effective in improving health behaviors and health knowledge of participating children, which may serve as a model for sustainable global child health promotion program. Further research is needed to test its long-term effects on child health.
Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis
Authors: Pedersen Niels C , Kim Yunjeong , Liu Hongwei , Galasiti Kankanamalage Anushka C , Eckstrand Chrissy , Groutas William C , Bannasch Michael , Meadows Juliana M , Chang Kyeong-Ok 
Published: September 2017

Objectives The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). Methods Twenty cats from 3.3–82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. Results Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1–7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1–7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3–4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5–14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16–18 weeks of age. Conclusions and relevance GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.
Sleep disordered breathing controlled by CPAP and sFlt-1 in a pregnant patient with chronic hypertension: Case report and literature review
Authors: Daly Amy , Robertson Annette , Bobek Gabriele , Middleton Sally , Sullivan Colin , Hennessy Annemarie 
Published: September 2017

Background There is recent interest exploring the possible impact of sleep disordered breathing on the mechanisms of preeclampsia. A biomarker of preeclampsia, soluble fms-like tyrosine kinase-1, has come to prominence in recent years. The aim of this study was to investigate the relationship between continuous positive airway pressure treatment, sleep disordered breathing and soluble fms-like tyrosine kinase-1 concentrations during pregnancy. Methods A 38-year-old G1P0 presented at 20 + 5 weeks. She had a history of chronic hypertension. Sleep studies revealed she had sleep disordered breathing with an AHI of 7.3/h. She was commenced on continuous positive airway pressure. Soluble fms-like tyrosine kinase-1 concentrations and blood pressure recordings were taken at various points during her pregnancy. Results She did not develop preeclampsia or require an escalation in her antihypertensives. Soluble fms-like tyrosine kinase-1 concentrations rose 16% from a low baseline. She remained compliant with her continuous positive airway pressure. She progressed to birth a well, live, term baby. Conclusion Continuous positive airway pressure treatment controlled sleep disordered breathing in a high risk pregnant woman with chronic hypertension with no increase in soluble fms-like tyrosine kinase-1 concentrations.
Galectin-3, a marker of cardiac remodeling, is inversely related to serum levels of marine omega-3 fatty acids. A cross-sectional study
Authors: Laake K , Seljeflot I , Schmidt EB , Myhre P , Tveit A , Norseth J , Arnesen H , Solheim S 
Published: September 2017

Objective Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. Setting From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2–8 weeks after the index acute myocardial infarction. Results Gal-3 was inversely correlated to eicosapentaenoic acid (r = −.120, p = .039) and docosahexaenoic acid (r = −.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). Conclusions The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.
Low-Dose Computed Tomographic Imaging of Partial Anomalous Pulmonary Venous Connection in Children
Authors: Türkvatan Aysel , Tola Hasan Tahsin , Kutlutürk Neşe , Güzeltaş Alper , Ergül Yakup 
Published: September 2017

Background: In this study, we aimed to determine lobar distribution, drainage sites, and associated cardiovascular anomalies of partial anomalous pulmonary venous connection in pediatric patients using low-dose multidetector computed tomographic angiography. Methods: Sixty-one cases (27 female, mean age: 4.7 years) with partial anomalous pulmonary venous connection diagnosed by multidetector computed tomographic angiography were included in this study. In all patients, multidetector computed tomographic angiography examinations were performed using dual-source 256-slice scanner without sedation. Results: In 61 patients, 73 anomalous pulmonary veins were detected, 56 (77%) of them were right-sided and 17 (23%) were left-sided. Of 56 right-sided anomalous pulmonary veins in 49 patients, 38 (68%) drained into superior vena cava, eight (14%) into atriocaval junction, six (11%) into inferior vena cava, three (5%) into right atrium, and one (2%) into levoatriocardinal vein. Of 17 left-sided anomalous pulmonary veins in 12 patients, 16 (94%) drained into left innominate vein, and one (6%) into coronary sinus. Only seven (12%) patients had isolated partial anomalous pulmonary venous connection, whereas 54 (88%) patients had additional cardiovascular anomalies. The most common (66%) associated anomaly is atrial septal defect. The overall mean effective radiation dose was 1.12 mSv (range: 0.15-7.41 mSv), and it was 0.58 mSv (range: 0.15-0.73) in the patients younger than one-year old. Conclusions: The presence and course of the anomalous pulmonary veins and associated cardiovascular anomalies can be reliably detected by dual-source 256-slice multidetector computed tomographic angiography with low radiation doses.
Single-Stage Repair of Coarctation of the Aorta and Ventricular Septal Defect: A Comparison of Surgical Strategies and Resource Utilization
Authors: Callahan Connor , Saudek David , Shillingford Amanda , Creighton Sara , Hill Garick , Johnson William , Tweddell James S. , Mitchell Michael E. , Woods Ronald K. 
Published: September 2017

Background: We sought to compare clinical outcomes and resource utilization for two surgical approaches for single-stage repair of coarctation of the aorta and ventricular septal defect (VSD). Methods: This was a retrospective chart review of 21 consecutive neonates and infants undergoing single-stage repair of coarctation of the aorta and VSD. Group 1 included 13 patients with both arch repair and VSD repair completed via sternotomy. Group 2 included eight patients with off-pump arch repair via left thoracotomy followed by repositioning and VSD repair via sternotomy. Primary clinical outcome was arch reintervention. Secondary outcomes included various measures of resource utilization. Results: Group 1 patients demonstrated younger age at repair (median of 10 days vs 57 days for group 2; P = .05) and lower proximal arch z scores (−4.2 vs −2.3 for group 2; P = .003). Arch reintervention occurred in 0 of 8 patients in group 2 and 1 (7.7%) of 13 patients in group 1 ( P = nonsignificant). Group 2 was associated with lower total charges (US$68,301 vs US$211,723 for group 1; P = .0007), shorter length of stay (8 days vs 23 days for group 1; P = .004), and shorter duration of postoperative mechanical ventilation (0.5 days vs 4.0 days for group 1; P = .0008). Group 2 was also associated with shorter total cardiopulmonary bypass time (86 minutes vs 201 minutes for group 1; P = .0009). Conclusion: Single-stage two-incision repair of coarctation and VSD in appropriately selected patients may be associated with higher value of care. Confirmation of this finding will require further study based on larger numbers of patients.