bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated classification of pain perception using high-density electroencephalography data
Authors: Misra Gaurav , Wang Wei-en , Archer Derek B. , Roy Arnab , Coombes Stephen A. 
Published: December 2016

The translation of brief, millisecond-long pain-eliciting stimuli to the subjective perception of pain is associated with changes in theta, alpha, beta, and gamma oscillations over sensorimotor cortex. However, when a pain-eliciting stimulus continues for minutes, regions beyond the sensorimotor cortex, such as the prefrontal cortex, are also engaged. Abnormalities in prefrontal cortex have been associated with chronic pain states, but conventional, millisecond-long EEG paradigms do not engage prefrontal regions. In the current study, we collected high-density EEG data during an experimental paradigm in which subjects experienced a 4-s, low- or high-intensity pain-eliciting stimulus. EEG data were analyzed using independent component analyses, EEG source localization analyses, and measure projection analyses. We report three novel findings. First, an increase in pain perception was associated with an increase in gamma and theta power in a cortical region that included medial prefrontal cortex. Second, a decrease in lower beta power was associated with an increase in pain perception in a cortical region that included the contralateral sensorimotor cortex. Third, we used machine learning for automated classification of EEG data into low- and high-pain classes. Theta and gamma power in the medial prefrontal region and lower beta power in the contralateral sensorimotor region served as features for classification. We found a leave-one-out cross-validation accuracy of 89.58%. The development of biological markers for pain states continues to gain traction in the literature, and our findings provide new information that advances this body of work.NEW & NOTEWORTHY The development of a biological marker for pain continues to gain traction in literature. Our findings show that high- and low-pain perception in human subjects can be classified with 89% accuracy using high-density EEG data from prefrontal cortex and contralateral sensorimotor cortex. Our approach represents a novel neurophysiological paradigm that advances the literature on biological markers for pain.
Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer
Authors: Hosford Sarah R. , Dillon Lloye M. , Bouley Stephanie J. , Rosati Rachele , Yang Wei , Chen Vivian S. , Demidenko Eugene , Morra Rocco P. , Miller Todd W. 
Published: December 2016

Abstract
Purpose: Determine the roles of the PI3K isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors.
Experimental Design: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen–resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations. Temporal response to growth factor receptor–initiated signaling, growth, apoptosis, predictive biomarkers, and tumor volumes were measured.
Results: p110β primed cells for response to growth factor stimulation. Although p110β inhibition suppressed cell and tumor growth, dual targeting of p110α/β enhanced apoptosis and provided sustained tumor response. The growth of anti-estrogen–sensitive cells was inhibited by fulvestrant, but fulvestrant inconsistently provided additional therapeutic effects beyond PI3K inhibition alone. Treatment-induced decreases in phosphorylation of AKT and Rb were predictive of therapeutic response. Short-term drug treatment induced tumor cell apoptosis and proliferative arrest to induce tumor regression, whereas long-term treatment only suppressed proliferation to provide durable regression.
Conclusions: p110β is the dominant PI3K isoform in PTEN-deficient, ER+ breast cancer cells. Upon p110β inhibition, p110α did not induce significant reactivation of AKT, but combined targeting of p110α/β most effectively induced apoptosis in vitro and in vivo and provided durable tumor regression. Because apoptosis and tumor regression occurred early but not late in the treatment course, and proliferative arrest was maintained throughout treatment, p110α/β inhibitors may be considered short-term cytotoxic agents and long-term cytostatic agents. Clin Cancer Res; 23(11); 2795–805. ©2016 AACR.
Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers
Authors: Van Roosbroeck Katrien , Fanini Francesca , Setoyama Tetsuro , Ivan Cristina , Rodriguez-Aguayo Cristian , Fuentes-Mattei Enrique , Xiao Lianchun , Vannini Ivan , Redis Roxana S. , D'Abundo Lucilla , Zhang Xinna , Nicoloso Milena S. , Rossi Simona , Gonzalez-Villasana Vianey , Rupaimoole Rajesha , Ferracin Manuela , Morabito Fortunato , Neri Antonino , Ruvolo Peter P. , Ruvolo Vivian R. , Pecot Chad V. , Amadori Dino , Abruzzo Lynne , Calin Steliana , Wang Xuemei , You M. James , Ferrajoli Alessandra , Orlowski Robert , Plunkett William , Lichtenberg Tara M. , Davuluri Ramana V. , Berindan-Neagoe Ioana , Negrini Massimo , Wistuba Ignacio I. , Kantarjian Hagop M. , Sood Anil K. , Lopez-Berestein Gabriel , Keating Michael J. , Fabbri Muller , Calin George A. 
Published: December 2016

Abstract
Purpose: The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors.
Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.
Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that anti-miR-155-DOPC can be considered non-toxic in vivo. We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer.
Conclusions: Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death. Clin Cancer Res; 23(11); 2891–904. ©2016 AACR.
ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer
Authors: Blaj Cristina , Bringmann Agnes , Schmidt Eva Marina , Urbischek Manuela , Lamprecht Sebastian , Fröhlich Thomas , Arnold Georg J. , Krebs Stefan , Blum Helmut , Hermeking Heiko , Jung Andreas , Kirchner Thomas , Horst David 
Published: December 2016

Abstract
Purpose: Constitutively active WNT signaling is a hallmark of colorectal cancers and a driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here, we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer.
Experimental Design: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer and cell biology approaches to determine its function. We induced ADNP expression in colon cancer xenografts by low-dose ketamine in vivo. Clinical associations were determined in a cohort of 221 human colorectal cancer cases.
Results: ADNP was overexpressed in colon cancer cells with high WNT activity, where it acted as a WNT repressor. Silencing ADNP expression increased migration, invasion, and proliferation of colon cancer cells and accelerated tumor growth in xenografts in vivo. Treatment with subnarcotic doses of ketamine induced ADNP expression, significantly inhibited tumor growth, and prolonged survival of tumor-bearing animals. In human patients with colon cancer, high ADNP expression was linked to good prognosis.
Conclusions: Our findings indicate that ADNP is a tumor suppressor and promising prognostic marker, and that ketamine treatment with ADNP induction is a potential therapeutic approach that may add benefit to current treatment protocols for patients with colorectal cancer. Clin Cancer Res; 23(11); 2769–80. ©2016 AACR.
Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice
Authors: Zimmermann Maike , Wang Si-Si , Zhang Hongyong , Lin Tzu-yin , Malfatti Michael , Haack Kurt , Ognibene Ted , Yang Hongyuan , Airhart Susan , Turteltaub Kenneth W. , Cimino George D. , Tepper Clifford G. , Drakaki Alexandra , Chamie Karim , de Vere White Ralph , Pan Chong-xian , Henderson Paul T. 
Published: December 2016

Abstract
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376–87. ©2016 AACR.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues
Authors: Lin Xiaoyu , Huang Xiaoli , Uziel Tamar , Hessler Paul , Albert Daniel H. , Roberts-Rapp Lisa A. , McDaniel Keith F. , Kati Warren M. , Shen Yu 
Published: December 2016

Abstract
An increasing number of BET family protein inhibitors have recently entered clinical trials. It has been reported that attempts of monitoring target engagement of the BET bromodomain inhibitor OTX015 using literature-described putative pharmacodynamic markers, such as c-Myc, BRD2, etc., failed to detect pharmacodynamic marker responses in AML patients treated at active dose and those with clinical responses. Here, we report the identification and characterization of HEXIM1 and other genes as robust pharmacodynamic markers for BET inhibitors. Global gene expression profiling studies were carried out using cancer cells and surrogate tissues, such as whole blood and skin, to identify genes that are modulated by BET family proteins. Candidate markers were further characterized for concentration- and time-dependent responses to the BET inhibitor ABBV-075 in vitro and in vivo. HEXIM1 was found to be the only gene that exhibited robust and consistent modulation by BET inhibitors across multiple cancer indications and surrogate tissues. Markers such as SERPINI1, ZCCHC24, and ZMYND8 were modulated by ABBV-075 and other BET inhibitors across cancer cell lines and xenograft tumors but not in blood and skin. Significant downregulation of c-Myc, a well-publicized target of BET inhibitors, was largely restricted to hematologic cancer cell lines. Incorporating well-characterized pharmacodynamic markers, such as HEXIM1 and other genes described here, can provide a better understanding of potential efficacy and toxicity associated with inhibiting BET family proteins and informs early clinical decisions on BET inhibitor development programs. Mol Cancer Ther; 16(2); 388–96. ©2016 AACR.
Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor
Authors: Wu Tingyu , Chen Wei , Zhong Yongwang , Hou Xiaodan , Fang Shengyun , Liu Chen-Ying , Wang Guanghui , Yu Tong , Huang Yu-Yang , Ouyang Xuesong , Li Henry Q.X. , Cui Long , Yang Yili 
Published: December 2016

Abstract
Although proteasome inhibitors such as bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a monotherapy for solid tumors, including colorectal cancer. We found in this study that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of bortezomib on colon cancer cells containing wild-type p53, which underwent G2–M cell-cycle block and apoptosis. Further analysis indicated that tumor suppressor p53 was one of the proteins exported from nuclei upon proteasome inhibition, and in the presence of CRM1 inhibitor KPT330, nuclear p53, and expression of its target genes were increased markedly. Moreover, knockdown of p53 significantly reduced the synergistic cytotoxic action of bortezomib and KPT330 on p53+/+ HCT116 cells. In mice, KPT330 markedly augmented the antitumor action of bortezomib against HCT116 xenografts as well as patient-derived xenografts that harbored functional p53. These results indicate that nuclear p53 is a major mediator in the synergistic antitumor effect of bortezomib and KPT330, and provides a rationale for the use of proteasome inhibitor together with nuclear export blocker in the treatment of colorectal cancer. It is conceivable that targeting nuclear exportation may serve as a novel strategy to overcome resistance and raise chemotherapeutic efficacy, especially for the drugs that activate the p53 system. Mol Cancer Ther; 16(4); 717–28. ©2016 AACR.
The impact of CD4+CD28null T-lymphocytes on atrial fibrillation and mortality in patients with chronic heart failure
Authors: Sulzgruber Patrick , Koller Lorenz , Winter Max-Paul , Richter Bernhard , Blum Steffen , Korpak Magdalena , Hülsmann Martin , Goliasch Georg , Wojta Johann , Niessner Alexander 
Published: December 2016

SummaryAtrial fibrillation (AF) represents the most common cardiac arrhythmia. Especially in patients with chronic heart failure (CHF) the development of AF represents a severe complication resulting in haemodynamic deterioration. While pro-inflammatory cytokines proved to have a pivotal role in the development and progression of both AF and CHF, less attention has been paid to the cellular immunity. Therefore we prospectively enrolled 112 patients with CHF and performed fluorescein-activated cell sorting (FACS). Patients were stratified in two subgroups according to patients presenting with AF (n=56) and patients free of AF (n=56). Comparing AF to non-AF patients we found a significantly lower fraction of regulatory T cells (p<0.001) in patients presenting with AF. However there was a higher fraction of CD4+ cells (p=0.007) and more specifically a significantly higher number of cytotoxic T cells characterised by the loss of CD28 within CD4 T cells (CD4+CD28null; p=0.035) in individuals with AF. After a mean follow-up time of 4.5 years 32 (28.6 %) patients died due to cardiovascular causes. CD4+CD28null cells were significantly associated with cardiovascular mortality in patients presenting with AF, with an adjusted HR per one standard deviation (1-SD) of 1.59 (95 % CI 1.13–2.24; p=0.008), but not in patients free of AF with an adjusted HR per 1-SD of 1.27 (95 % CI 0.86–1.87; p=0.216). We found that the fraction of CD4+CD28null cells proved to be predictive on outcome in CHF-patients presenting with AF. Our results might indicate a potential role of CD4+CD28null cells in the pathogenesis of AF which needs to be confirmed in future studies.Supplementary Material to this article is available online at www.thrombosis-online.com.
Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score
Authors: Brascia Debora , Onorati Francesco , Reichart Daniel , Perrotti Andrea , Ruggieri Vito G. , Santarpino Giuseppe , Maselli Daniele , Mariscalco Giovanni , Gherli Riccardo , Rubino Antonino S. , De Feo Marisa , Gatti Giuseppe , Santini Francesco , Dalén Magnus , Saccocci Matteo , Kinnunen Eeva-Maija , Airaksinen Juhani K. E. , D’Errigo Paola , Rosato Stefano , Nicolini Francesco , Biancari Fausto 
Published: December 2016

SummarySevere perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2–3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0–3: 2.9 % vs 3.4 %; scores 4–6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.Clinical Trial Registration: NCT02319083 (https://clinicaltrials.gov/ct2/show/NCT02319083)
Trends in Testing for Mycobacterium tuberculosis Complex From US Public Health Laboratories, 2009–2013
Authors: Tyrrell Frances , Stafford Cortney , Yakrus Mitchell , Youngblood Monica , Hill Andrew , Johnston Stephanie 
Published: December 2016

Objective: We investigated data from US public health laboratories funded through the Centers for Disease Control and Prevention’s Tuberculosis Elimination and Laboratory Cooperative Agreement to document trends and challenges in meeting national objectives in tuberculosis (TB) laboratory diagnoses. Methods: We examined data on workload and turnaround time from public health laboratories’ progress reports during 2009-2013. We reviewed methodologies, laboratory roles, and progress toward rapid detection of Mycobacterium tuberculosis complex through nucleic acid amplification (NAA) testing. We compared selected data with TB surveillance reports to estimate public health laboratories’ contribution to national diagnostic services. Results: During the study period, culture and drug susceptibility tests decreased, but NAA testing increased. Public health laboratories achieved turnaround time benchmarks for drug susceptibility tests at lower levels than for acid-fast bacilli smear and identification from culture. NAA positivity in laboratories among surveillance-reported culture-positive TB cases increased from 26.6% (2355 of 8876) in 2009 to 40.0% (2948 of 7358) in 2013. Public health laboratories provided an estimated 50.9% (4285 of 8413 in 2010) to 57.2% (4210 of 7358 in 2013) of culture testing and 88.3% (6822 of 7727 in 2011) to 94.4% (6845 of 7250 in 2012) of drug susceptibility tests for all US TB cases. Conclusions: Public health laboratories contribute substantially to TB diagnoses in the United States. Although testing volumes mostly decreased, the increase in NAA testing indicates continued progress in rapid M tuberculosis complex detection.
Effect of wetting time in the sorption and in the thermal conductivity of the most commonly used structural materials
Authors: Szodrai Ferenc , Lakatos Ákos 
Published: December 2016

During the thermal assessment of buildings, proper understanding and knowledge of the thermal behavior of the materials is required. Certain indoor and outdoor conditions can cause moisture transfer and could change the thermal properties of buildings (e.g. thermal conductivity, resistance, thermal diffusivity, specific heat capacity, etc.). In this technical note, a research report can be found on the measured thermal conductivity after drying and wetting the samples. For the measurements, we used a dry-heat laboratory oven (Venticell 111) apparatus to dry the samples and a climatic chamber (Climacell 111) to wet the materials in order to get the values. By applying these two chambers, we were able to reach the moisture content of different humidity levels and create the kinetic wetting curves for each sample. To measure the thermal conductivity, a heat flow meter type Holometrix 2000 was used. During the measurements, five different types of materials were used (solid brick, lightweight and foam concrete, plasterboard, corkboard). In order to reach acceptable accuracy, three measurement series were carried out on the samples at each wetting times. During one series, the thermal conductivity was measured 10 times, and the average of the 13 thermal conductivity results gave the final value. Moreover, from the measurement results, new equations and functions were created to show the relationship between the thermal conductivity and the moisture content of the materials. Our results showed that after wetting the samples in a climatic chamber at 293 K and at 90% relative humidity, the kinetic function (time dependence) of adsorbed water increased in the cases of all the materials used; however, thermal conductivity only increased considerably in the cases of the two different types of concrete and of the plasterboard. Practical application: The role of insulation materials in the building energy and moisture balance is more significant compared to the other materials of the building structures. The high moisture load will require the change of the thermal parameters of the materials. Moisture is a common cause of building degradation. In fact, much of what we know about applied building science today originates from early work investigating moisture impact on buildings, while the severity of moisture problems varies greatly depending on climate. These estimations based on the laboratory measurements of these values of the insulating materials are very important either for the manufacturers or the contractors, planners, and designers.