bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer Aggressiveness by Ambient Ionization Mass Spectrometry Imaging
Authors: Sans Marta , Gharpure Kshipra , Tibshirani Robert , Zhang Jialing , Liang Li , Liu Jinsong , Young Jonathan H. , Dood Robert L. , Sood Anil K. , Eberlin Livia S. 
Published: April 2017

AbstractOvarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management. Here, we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image and chemically characterize the metabolic profiles of HGSC, BOT, and normal ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine papillary branches in serous BOT and allowed for characterization of spatial features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC. Predictive markers of cancer aggressiveness were identified, including various free fatty acids, metabolites, and complex lipids such as ceramides, glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification models built from a total of 89,826 individual pixels, acquired in positive and negative ion modes from 78 different tissue samples, enabled diagnosis and prediction of HGSC and all tumor samples in comparison with normal tissues, with overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination was achieved with an overall accuracy of 93.0%. Interestingly, our classification model allowed identification of three BOT samples presenting unusual histologic features that could be associated with the development of low-grade carcinomas. Our results suggest DESI-MS as a powerful approach for rapid serous ovarian cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903–13. ©2017 AACR.
TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative Breast Cancers via Regulating Alternative Splicing
Authors: Liu Tieju , Sun Huizhi , Zhu Dongwang , Dong Xueyi , Liu Fang , Liang Xiaohui , Chen Chen , Shao Bing , Wang Meili , Wang Yi , Sun Baocun 
Published: April 2017

Abstract
Treatment of triple-negative breast cancer (TNBC) has been challenging, and paclitaxel resistance is one of the major obstacles to the better prognosis. Deregulation of alternative splicing (AS) may contribute to tumor progression and chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival and therapeutic sensitivity. However, the individual role of TRA2A in cancer progression has not been reported. Here we report that TRA2A facilitates proliferation and survival and migration and invasion of TNBC cells. In addition, TRA2A promotes paclitaxel resistance of TNBC by specifically controlling cancer-related splicing, which is independent of other splicing factors. TRA2A overexpression could promote AS of CALU, RSRC2, and PALM during paclitaxel treatment of TNBC cells. The isoform shift of RSRC2 from RSRC2s to RSRC2l leads to a decreased RSRC2 protein expression, which could contribute to TNBC paclitaxel resistance. TRA2A can regulate RSRC2 AS by specifically binding upstream intronic sequence of exon4. Strikingly, TRA2A expression is increased dramatically in patients with TNBC, and has a close relationship with decreased RSRC2 expression; both are associated with poor survival of TNBC. Collectively, our findings suggest that paclitaxel targets the TRA2A–RSRC2 splicing pathway, and deregulated TRA2A and RSRC2 expression may confer paclitaxel resistance. In addition to providing a novel molecular mechanism of cancer-related splicing dysregulation, our study demonstrates that expression of TRA2A in conjunction with RSRC2 may provide valuable molecular biomarker evidence for TNBC clinical treatment decisions and patient outcome. Mol Cancer Ther; 16(7); 1377–88. ©2017 AACR.
Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes
Authors: Mosley Jonathan D. , Shoemaker M. Benjamin , Wells Quinn S. , Darbar Dawood , Shaffer Christian M. , Edwards Todd L. , Bastarache Lisa , McCarty Catherine A. , Thompson Will , Chute Christopher G. , Jarvik Gail P. , Crosslin David R. , Larson Eric B. , Kullo Iftikhar J. , Pacheco Jennifer A. , Peissig Peggy L. , Brilliant Murray H. , Linneman James G. , Witte John S. , Denny Josh C. , Roden Dan M. 
Published: April 2017

Background—
One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability.

Methods and Results—

We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=−0.88;
P
=0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47;
P
=0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83–0.95;
P
=0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=−0.03 [0.16]).

Conclusions—
The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity.
Determining a Successful Nasal Airway Surgery: Calculation of the Patient‐Centered Minimum Important Difference
Authors: Ziai Hedyeh , Bonaparte James P. 
Published: April 2017

ObjectiveDetermine whether the patient‐identified minimum important difference (MID) in Nasal Obstruction Symptom Evaluation (NOSE) score differs from a statistically calculated estimate of MID in patients with septal deviation undergoing nasal airway surgery.Study DesignProspective cohort.SettingTertiary academic referral center.SubjectsPatients with nasal obstruction due to septal deviation.MethodsPatients completed the NOSE questionnaire preoperatively and indicated the change from their baseline score that they would consider the minimum improvement required to define the septoplasty with turbinate reduction as successful. A previously published distribution‐based approach was used to estimate the MID based on baseline NOSE scores. Scores were reported both as a raw score and as a percentage of patients’ baseline scores. One‐sample t test was used to compare the statistically estimated MID to the patient‐reported MID.ResultsSeventy‐six patients were included. The mean (SD) baseline NOSE score was 12.9 (4.03). The mean (SD) patient‐identified MID was 5.3 (2.1), corresponding to a 41.1% change (95% confidence interval, 37.2‐41.3) from baseline. The statistically estimated MID was 5.2 points (40.3% reduction from baseline scores). The estimated MID was not significantly different from the patient‐identified MID (P =. 4).ConclusionIn patients with septal deviation, an improvement of approximately 40% in their nasal obstructive symptoms as assessed by the NOSE questionnaire is required to define a nasal airway surgery as successful. The patient‐identified and the statistically calculated MIDs were similar. Furthermore, this MID can be used to guide research, improving the ability to use the NOSE score as a dichotomous scoring measure (treatment success/failure) and estimating sample size.
Effects of Silver Nitrate Cauterization on Middle Turbinate Synechia after Endoscopic Sinus Surgery
Authors: Uluyol Sinan 
Published: April 2017

ObjectiveThis study aimed to examine the efficacy of silver nitrate cauterization of the middle turbinate (MT) for hindering postoperative middle meatal synechia formation after endoscopic sinus surgery (ESS).Study DesignProspective, controlled, and single‐blinded.SettingsTertiary referral center.Subjects and MethodsFor this study, 38 patients undergoing bilateral ESS due to nasal polyposis were recruited. Following ESS, silver nitrate cauterization of the lateral side of the left MT was performed in all cases. The noncauterized opposite right sides served as controls. All patients received the standard ESS protocol, intraoperative middle meatal packing, and postoperative management. The main outcome measured was the formation of partial or complete MT synechia at the end of 6‐month assessment, performed by a blinded observer.ResultsAt the end of the 6‐month follow‐up period, MT synechia formation was observed in 7 of the right sides (7 of 38, 18.4%) and none in any left sides. The rate of synechia formation was significantly higher in the controls when compared with the silver nitrate–cauterized sides (P <. 001).ConclusionThe results of this study suggest that silver nitrate cauterization of the MT is a practical and efficient method to eliminate middle meatal synechia after ESS.
Detecting Myocardial Ischemia With 99mTechnetium-Tetrofosmin Myocardial Perfusion Imaging in Ischemic Stroke
Authors: Giannopoulos Sotirios , Markoula Sofia , Sioka Chrissa , Zouroudi Sofia , Spiliotopoulou Maria , Naka Katerina K. , Michalis Lampros K. , Fotopoulos Andreas , Kyritsis Athanassios P. 
Published: April 2017

Background: To assess the myocardial status in patients with stroke, employing myocardial perfusion imaging (MPI) with 99mTechnetium-tetrofosmin (99mTc-TF)-single-photon emission computed tomography (SPECT). Methods: Fifty-two patients with ischemic stroke were subjected to 99mTc-TF-SPECT MPI within 1 month after stroke occurrence. None of the patients had any history or symptoms of coronary artery disease or other heart disease. Myocardial perfusion imaging was evaluated visually using a 17-segment polar map. Myocardial ischemia (MIS) was defined as present when the summed stress score (SSS) was >4; MIS was defined as mild when SSS was 4 to 8, and moderate/severe with SSS ≥9. Patients with SSS >4 were compared to patients with SSS <4. Parameters such as age, body mass index, waist perimeter, smoking habits, and medical history (diabetes mellitus, dyslipidemia, etc) were evaluated according to MPI results. Results: Myocardial ischemia was present in 32 (62%) of 52 patients with stroke. Among them, 20 (62%) of 32 patients had mild abnormalities and 12 (38%) of 32 had moderate/severe. The age and waist perimeter showed a tendency to relate to severe MIS when patients with SSS >9 were compared to patients with SSS <4. In MPI-positive patients, an age was to be association with SSS, with the oldest age exhibiting the highest SSS ( P = .01). The association of age with SSS remained statistically significant in the multivariate analysis ( P = .04). Conclusion: The study suggested that more than half of patients with stroke without a history of cardiac disease have MIS. Although most of them have mild MIS, we suggest a thorough cardiological evaluation in this group of patients for future prevention of severe myocardial outcome.
Inductive electromagnetic data interpretation using a 3D distribution of 3D magnetic or electric dipoles
Authors: Kolaj Michal , Smith Richard 
Published: April 2017

In inductive electromagnetics, the magnetic field measured in the air at any instant can be considered to be a potential field. As such, we can invert measured magnetic fields (at a fixed time or frequency) for the causative subsurface current system. These currents can be approximated with a 3D subsurface grid of 3D magnetic (closed-loop current) or electric (line current) dipoles whose location and orientation can be solved for using a potential-field-style smooth-model inversion. Because the problem is linear, both inversions can be solved quickly even for large subsurface volumes; and both can be run on a single data set for complementary information. Synthetic studies suggest that for discrete induction dominated targets, the magnetic and electric dipole inversions can be used to determine the center and top edge of the target, respectively. Furthermore, the orientation of plate targets can be estimated from visual examination of the orientations of the 3D vector dipoles and/or using the interpreted location of the center and top edge of the target. In the first field example, ground data from a deep massive sulfide body (mineral exploration target) was inverted and the results were consistent with the conclusions drawn from the synthetic examples and with the existing interpretation of the body (shallow dipping conductor at a depth of approximately 400 m). A second example over a near-surface mine tailing (a near-surface environmental/engineering study) highlighted the strength of being able to invert data using either magnetic or electric dipoles. Although both models were able to fit the data, the electric dipole model was considerably simpler and revealed a southwest−northeast-trending conductive zone. This fast approximate 3D inversion can be used as a starting point for more rigorous interpretation and/or, in some cases, as a stand-alone interpretation tool.
Randomized Controlled Trial of Survivorship Care Plans Among Low-Income, Predominantly Latina Breast Cancer Survivors
Authors: Maly Rose C. , Liang Li-Jung , Liu Yihang , Griggs Jennifer J. , Ganz Patricia A. 
Published: April 2017

Purpose The purpose of this study was to examine the effects of a randomized controlled trial (RCT) of treatment summaries and survivorship care plans coupled with a nurse counseling session, primarily on physician implementation of and secondarily on patient adherence to recommended survivorship care, among a low-income population of breast cancer survivors (survivors). Methods We recruited 212 low-income, predominantly Latina (72.6%) survivors with stage 0 to III breast cancer, with an average age of 53 years, from two Los Angeles County public hospitals into an RCT of a survivorship care nurse counseling session coupled with the provision of individualized treatment summaries and survivorship care plans to patients and their health care providers from December 2012 to July 2014. One hundred seven survivors received the experimental intervention, and 105 survivors received usual care. Multiple linear regression analyses were performed to assess intervention effects on physician implementation of and patient adherence to recommended survivorship care. Scales that served as covariables were Knowledge of Survivorship Issues, Perceived Efficacy in Patient-Physician Interactions, and Satisfaction With Care and Information. Results Survivors in the intervention group reported greater physician implementation of recommended breast cancer survivorship care, for example, treatment of depression or hot flashes, than did those in the control group (adjusted difference, 16 ± 5.3; P = .003). Baseline Satisfaction With Care and Information was positively associated with physician implementation (coefficient, 5.2 ± 2.2; P = .02). Being married/partnered (−11.8 ± 4.0; P = .004) and age (−0.5 ± 0.2; P = .028) were negatively associated with patient adherence. Conclusion To our knowledge, this is the first RCT of survivorship care plans to show benefits in clinical outcomes, in this case, showing increased physician implementation of recommended breast cancer survivorship care in the intervention group, compared with the control group.
Video-Teleconferencing in Pediatric Neuro-Oncology: Ten Years of Experience
Authors: Amayiri Nisreen , Swaidan Maisa , Abuirmeileh Najiyah , Al-Hussaini Maysa , Tihan Tarik , Drake James , Musharbash Awni , Qaddoumi Ibrahim , Tabori Uri , Halalsheh Hadeel , Bartels Ute , Bouffet Eric 
Published: April 2017

Purpose The management of central nervous system tumors is challenging in low- and middle-income countries. Little is known about applicability of twinning initiatives with high-income countries in neuro-oncology. In 2004, a monthly neuro-oncology video-teleconference program was started between King Hussein Cancer Center (Amman, Jordan) and the Hospital for Sick Children (Toronto, Ontario, Canada). More than 100 conferences were held and > 400 cases were discussed. The aim of this work was to assess the sustainability of such an initiative and the evolution of the impact over time. Methods We divided the duration in to three eras according to the initial 2 to 3 years of work of three consecutive oncologists in charge of the neuro-oncology program at King Hussein Cancer Center. We retrospectively reviewed the written minutes and compared the preconference suggested plans with the postconference recommendations. Impact of changes on the patient care was recorded. Results Thirty-three sets of written minutes (covering 161 cases) in the middle era and 32 sets of written minutes (covering 122 cases) in the last era were compared with the initial experience (20 meetings, 72 cases). Running costs of these conferences has dropped from $360/h to < $40/h. Important concepts were introduced, such as multidisciplinary teamwork, second-look surgery, and early referral. Suggestions for plan changes have decreased from 44% to 30% and 24% in the respective consecutive eras. Most recommendations involved alternative intervention modalities or pathology review. Most of these recommendations were followed. Conclusion Video-teleconferencing in neuro-oncology is feasible and sustainable. With time, team experience is built while the percentage and the type of treatment modifications change. Commitment and motivation helped maintain this initiative rather than availability of financial resources. Improvement in patients’ care was achieved, in particular, with the implementation of a multidisciplinary team and the continuous effort to implement recommendations.
Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial
Authors: Cutler Antony J. , Oliveira Joao , Ferreira Ricardo C. , Challis Ben , Walker Neil M. , Caddy Sarah , Lu Jia , Stevens Helen E. , Smyth Deborah J. , Pekalski Marcin L. , Kennet Jane , Hunter Kara M.D. , Goodfellow Ian , Wicker Linda S. , Todd John A. , Waldron-Lynch Frank 
Published: April 2017

Background: The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen.Methods: Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel.Results: Norovirus infection was self-limited and resolved within 24 hours, with the subsequent development of anti-norovirus antibodies. Serum pro- and anti-inflammatory cytokine levels, including IL-10, peaked during the symptomatic period of infection, coincident with increased frequencies of monocytes and neutrophils. At the same time, the frequency of regulatory CD4+T cell (Treg), effector T cell (Teff) CD4+and CD8+subsets were dynamically reduced, rebounding to baseline levels or above at the next sampling point 24 hours later. NK cells and NKT cells transiently increased CD69 expression and classical monocytes expressed increased levels of CD40, HLA-DR and SIGLEC-1, biomarkers of an interferon response. We also observed activation and mobilisation of Teffs, where increased frequencies of CD69+and Ki-67+effector memory Teffs were followed by the emergence of memory CD8+Teff expressing the mucosal tissue homing markers CD103 and β7 integrin. Treg responses were coincident with the innate cell, Teff and cytokine response. Key Treg molecules FOXP3, CTLA-4, and CD25 were upregulated following infection, alongside an increase in frequency of Tregs with the capacity to home to tissues.Conclusions: The results illustrate the innate, adaptive and counter-regulatory immune responses to norovirus infection. Low-dose IL-2 administration induces many of the Treg responses observed during infection.
Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's Disease
Authors: Cole Scott R. , van der Meij Roemer , Peterson Erik J. , de Hemptinne Coralie , Starr Philip A. , Voytek Bradley 
Published: April 2017

Oscillations in neural activity play a critical role in neural computation and communication. There is intriguing new evidence that the nonsinusoidal features of the oscillatory waveforms may inform underlying physiological and pathophysiological characteristics. Time-domain waveform analysis approaches stand in contrast to traditional Fourier-based methods, which alter or destroy subtle waveform features. Recently, it has been shown that the waveform features of oscillatory beta (13–30 Hz) events, a prominent motor cortical oscillation, may reflect near-synchronous excitatory synaptic inputs onto cortical pyramidal neurons. Here we analyze data from invasive human primary motor cortex (M1) recordings from patients with Parkinson's disease (PD) implanted with a deep brain stimulator (DBS) to test the hypothesis that the beta waveform becomes less sharp with DBS, suggesting that M1 input synchrony may be decreased. We find that, in PD, M1 beta oscillations have sharp, asymmetric, nonsinusoidal features, specifically asymmetries in the ratio between the sharpness of the beta peaks compared with the troughs. This waveform feature is nearly perfectly correlated with beta-high gamma phase-amplitude coupling (r= 0.94), a neural index previously shown to track PD-related motor deficit. Our results suggest that the pathophysiological beta generator is altered by DBS, smoothing out the beta waveform. This has implications not only for the interpretation of the physiological mechanism by which DBS reduces PD-related motor symptoms, but more broadly for our analytic toolkit in general. That is, the often-overlooked time-domain features of oscillatory waveforms may carry critical physiological information about neural processes and dynamics.SIGNIFICANCE STATEMENTTo better understand the neural basis of cognition and disease, we need to understand how groups of neurons interact to communicate with one another. For example, there is evidence that parkinsonian bradykinesia and rigidity may arise from an oversynchronization of afferents to the motor cortex, and that these symptoms are treatable using deep brain stimulation. Here we show that the waveform shape of beta (13–30 Hz) oscillations, which may reflect input synchrony onto the cortex, is altered by deep brain stimulation. This suggests that mechanistic inferences regarding physiological and pathophysiological neural communication may be made from the temporal dynamics of oscillatory waveform shape.