bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic Thyroid Cancer
Authors: Mehta Amit , Zhang Lisa , Boufraqech Myriem , Liu-Chittenden Yi , Zhang Yaqin , Patel Dhaval , Davis Sean , Rosenberg Avi , Ylaya Kris , Aufforth Rachel , Li Zhuyin , Shen Min , Kebebew Electron 
Published: May 2015

Abstract
Purpose: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without any effective therapy. The aim of this study is to use a high-throughput drug library screening to identify a novel therapeutic agent that targets dysregulated genes/pathways in ATC.
ExperimentalDesign: We performed quantitative high-throughput screening (qHTS) in ATC cell lines using a compound library of 3,282 drugs. Dysregulated genes in ATC were analyzed using genome-wide expression analysis and immunohistochemistry in human ATC tissue samples and ATC cell lines. In vitro and in vivo studies were performed for determining drug activity, effectiveness of targeting, and the mechanism of action.
Results: qHTS identified 100 active compounds in three ATC cell lines. One of the most active agents was the first-in-class survivin inhibitor YM155. Genome-wide expression analysis and immunohistochemistry showed overexpression of survivin in human ATC tissue samples, and survivin was highly expressed in all ATC cell lines tested. YM155 significantly inhibited ATC cellular proliferation. Mechanistically, YM155 inhibited survivin expression in ATC cells. Furthermore, YM155 treatment reduced claspin expression, which was associated with S-phase arrest in ATC cells. In vivo, YM155 significantly inhibited growth and metastases and prolonged survival.
Conclusions: Our data show that YM155 is a promising anticancer agent for ATC and that its target, survivin, is overexpressed in ATC. Our findings support the use of YM155 in clinical trials as a therapeutic option in advanced and metastatic ATC. Clin Cancer Res; 21(18); 4123–32. ©2015 AACR.
Differential Expression of Immune-Regulatory Genes Associated with PD-L1 Display in Melanoma: Implications for PD-1 Pathway Blockade
Authors: Taube Janis M. , Young Geoffrey D. , McMiller Tracee L. , Chen Shuming , Salas January T. , Pritchard Theresa S. , Xu Haiying , Meeker Alan K. , Fan Jinshui , Cheadle Chris , Berger Alan E. , Pardoll Drew M. , Topalian Suzanne L. 
Published: May 2015

Abstract
Purpose: Blocking the immunosuppressive PD-1/PD-L1 pathway has antitumor activity in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating myeloid cells correlates with the likelihood of response. We previously found that IFNG (interferon-gamma) was overexpressed by tumor-infiltrating lymphocytes in PD-L1+ versus PD-L1(−) melanomas, creating adaptive immune resistance by promoting PD-L1 display. This study was undertaken to identify additional factors in the PD-L1+ melanoma microenvironment coordinately contributing to immunosuppression.
Experimental Design: Archived, formalin-fixed paraffin-embedded melanoma specimens were assessed for PD-L1 protein expression at the tumor cell surface with IHC. Whole-genome expression analysis, quantitative (q)RT-PCR, IHC, and functional in vitro validation studies were used to assess factors differentially expressed in PD-L1+ versus PD-L1(−) melanomas.
Results: Functional annotation clustering based on whole-genome expression profiling revealed pathways upregulated in PD-L1+ melanomas, involving immune cell activation, inflammation, and antigen processing and presentation. Analysis by qRT-PCR demonstrated overexpression of functionally related genes in PD-L1+ melanomas, involved in CD8+ T-cell activation (CD8A, IFNG, PRF1, and CCL5), antigen presentation (CD163, TLR3, CXCL1, and LYZ), and immunosuppression [PDCD1 (PD-1), CD274 (PD-L1), and LAG3, IL10]. Functional studies demonstrated that some factors, including IL10 and IL32-gamma, induced PD-L1 expression on monocytes but not tumor cells.
Conclusions: These studies elucidate the complexity of immune checkpoint regulation in the tumor microenvironment, identifying multiple factors likely contributing to coordinated immunosuppression. These factors may provide tumor escape mechanisms from anti–PD-1/PD-L1 therapy, and should be considered for cotargeting in combinatorial immunomodulation treatment strategies. Clin Cancer Res; 21(17); 3969–76. ©2015 AACR.
Increasing Efforts to Reduce Cervical Cancer through State-Level Comprehensive Cancer Control Planning
Authors: Meyerson Beth E. , Zimet Gregory D. , Multani Gurprit S. , Levell Caleb , Lawrence Carrie A. , Smith Jennifer S. 
Published: May 2015

AbstractReducing cervical cancer disparities in the United States requires intentional focus on structural barriers such as systems and policy that impact access to human papillomavirus (HPV) vaccination, cervical cancer screening, and treatment. Such changes are difficult and often politicized. State comprehensive cancer control (CCC) plans are vehicles that, if designed well, can help build collective focus on structural changes. Study objectives were to identify the prioritization of cervical cancer in state CCC plans, the conceptualization of HPV within these plans, and the focus of plans on structural changes to reduce cervical cancer disparities. Data were gathered by systematic content analysis of CCC plans from 50 states and the District of Columbia from February–June 2014 for evidence of cervical cancer prioritization, conceptualization of HPV, and focus on structural barriers to cervical cancer vaccination, screening or treatment. Findings indicate that prioritization of cervical cancer within state CCC plans may not be a strong indicator of state efforts to reduce screening and treatment disparities. While a majority of plans reflected scientific evidence that HPV causes cervical and other cancers, they did not focus on structural elements impacting access to evidence-based interventions. Opportunities exist to improve state CCC plans by increasing their focus on structural interventions that impact cervical cancer prevention, detection, and treatment, particularly for the 41% of plans ending in 2015 and the 31% ending between 2016 and 2020. Future studies should focus on the use of policy tools in state CCC plans and their application to cervical cancer prevention and treatment. Cancer Prev Res; 8(7); 636–41. ©2015 AACR.
Patients’ and Providers’ Perspectives of a Polypill Strategy to Improve Cardiovascular Prevention in Australian Primary Health Care
Authors: Liu Hueiming , Massi Luciana , Laba Tracey-Lea , Peiris David , Usherwood Tim , Patel Anushka , Cass Alan , Eades Anne-Marie , Redfern Julie , Hayman Noel , Howard Kirsten , Brien Jo-anne , Jan Stephen 
Published: May 2015

Background—
This study explores health provider and patient attitudes toward the use of a cardiovascular polypill as a health service strategy to improve cardiovascular prevention.

Methods and Results—
In-depth, semistructured interviews (n=94) were conducted with health providers and patients from Australian general practice, Aboriginal community-controlled and government-run Indigenous Health Services participating in a pragmatic randomized controlled trial evaluating a polypill-based strategy for high-risk primary and secondary cardiovascular disease prevention. Interview topics included polypill strategy acceptability, factors affecting adherence, and trial implementation. Transcribed interview data were analyzed thematically and interpretively. Polypill patients commented frequently on cost-savings, ease, and convenience of a daily-dosing pill. Most providers considered a polypill strategy to facilitate improved patient medication use. Indigenous Health Services providers and indigenous patients thought the strategy acceptable and beneficial for indigenous patients given the high disease burden. Providers noted the inflexibility of the fixed dose regimen, with dosages sometimes inappropriate for patients with complex management considerations. Future polypill formulations with varied strengths and classes of medications may overcome this barrier. Many providers suggested the polypill strategy, in its current formulations, might be more suited to high-risk primary prevention patients.

Conclusions—
The polypill strategy was generally acceptable to patients and providers in cardiovascular prevention. Limitations to provider acceptability of this particular polypill were revealed, as was a perception it might be more suitable for high-risk primary prevention patients, though future combinations could facilitate its use in secondary prevention. Participants suggested a polypill-based strategy as particularly appropriate for lowering the high cardiovascular burden in indigenous populations.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au
. ANZCTRN: 12608000583347.
Pulmonary Congestion at Rest and Abnormal Ventilation During Exercise in Chronic Systolic Heart Failure
Authors: Malfatto Gabriella , Caravita Sergio , Giglio Alessia , Rossi Jessica , Perego Giovanni B. , Facchini Mario , Parati Gianfranco 
Published: May 2015

Background

In patients with chronic heart failure, abnormal ventilation at cardiopulmonary testing (expressed by minute ventilation‐to‐carbon dioxide production, or
VE
/
VCO
2
slope, and resting end‐tidal
CO
2
pressure) may derive either from abnormal autonomic or chemoreflex regulation or from lung dysfunction induced by pulmonary congestion. The latter hypothesis is supported by measurement of pulmonary capillary wedge pressure, which cannot be obtained routinely but may be estimated noninvasively by measuring transthoracic conductance (thoracic fluid content 1/kΩ) with impedance cardiography.

Methods and Results

Preliminarily, in 9 patients undergoing invasive hemodynamics during cardiopulmonary testing, we demonstrated a significant relationship between
VE
/
VCO
2
slope and resting end‐tidal
CO
2
pressure with baseline and peak pulmonary capillary wedge pressure. Later, noninvasive hemodynamic evaluation by impedance cardiography was performed before cardiopulmonary testing in 190 patients with chronic systolic heart failure and normal lung function (aged 67±3 years, 71% with ischemia, ejection fraction 32±7%, 69% with implantable cardioverter‐defibrillator or cardiac resynchronization therapy). In this group, we determined the relationship between abnormal ventilation (
VE
/
VCO
2
slope and resting end‐tidal
CO
2
pressure) and transthoracic conductance. In the whole population, thoracic fluid content values were significantly related to
VE
/
VCO
2
slope (
R
=0.63,
P
<0.0001) and to resting end‐tidal
CO
2
pressure (
R
=−0.44,
P
<0.001).

Conclusions
In patients with chronic heart failure, abnormal ventilation during exercise may be related in part to pulmonary congestion, as detected by resting baseline impedance cardiography.
Метод просопографии в изучении средневековой России
Authors: Rybalko Nataliia V. 
Published: May 2015

This article examines the application of the method of prosopography to solve problems in the study of medieval Russia. The author draws attention to the work of Russian historians who have used this method since the nineteenth century and describes the achievements of modern historians, including R.G. Skrynnikov. The article demonstrates how the method works by means of a case study of the system operating in Moscow’s municipal departments during the Time of Troubles. The reconstruction of 700 biographies of major and minor officials reveals that the crisis of the supreme power in Muscovy did not lead to the destruction of its institutions of administration.
Sensitivity of the Climate Response to the Altitude of Black Carbon in the Northern Subtropics in an Aquaplanet GCM
Authors: Kim Hanjun , Kang Sarah M. , Hwang Yen-Ting , Yang Young-Min 
Published: May 2015

Abstract
This study explores the dependence of the climate response on the altitude of black carbon in the northern subtropics by employing an atmospheric general circulation model coupled to an aquaplanet mixed layer ocean, with a focus on the pattern changes in the temperature, hydrological cycle, and large-scale circulation. Black carbon added below or within the subtropical low-level clouds tends to suppress convection, which reduces the low cloud amount, resulting in a positive cloud radiative forcing. The warmer northern subtropics then induce a northward shift of the intertropical convergence zone (ITCZ) and a poleward expansion of the descending branch of the northern Hadley cell. As the black carbon–induced local warming is amplified by clouds and is advected by the anomalous Hadley circulation, the entire globe gets warmer. In contrast, black carbon added near the surface increases the buoyancy of air parcels to enhance convection, leading to an increase in the subtropical low cloud amount and a negative cloud radiative forcing. The temperature increase remains local to where black carbon is added and elsewhere decreases, so that the ITCZ is shifted southward and the descending branch of the northern Hadley cell contracts equatorward. Consistent with previous studies, the authors demonstrate that the climate response to black carbon is highly sensitive to the vertical distribution of black carbon relative to clouds; hence, models have to accurately compute the vertical transport of black carbon to enhance their skill in simulating the climatic effects of black carbon.
Seasonal Dependence of the Effect of Arctic Greening on Tropical Precipitation
Authors: Kang Sarah M. , Kim Baek-Min , Frierson Dargan M. W. , Jeong Su-Jong , Seo Jeongbin , Chae Yoojeong 
Published: May 2015

Abstract
This paper examines the seasonal dependence of the effect of Arctic greening on tropical precipitation. In CAM3/CLM3 coupled to a mixed layer ocean, shrub and grasslands poleward of 60°N are replaced with boreal forests. With darker Arctic vegetation, the absorption of solar energy increases, but primarily in boreal spring and summer since little insolation reaches the Arctic in boreal winter. The net energy input into the northern extratropics is partly balanced by southward atmospheric energy transport across the equator by an anomalous Hadley circulation, resulting in a northward shift of the tropical precipitation. In contrast, in boreal fall, the slight increase in insolation over the Arctic is more than offset by increased outgoing longwave radiation and reduced surface turbulent fluxes in midlatitudes, from the warmer atmosphere. As a result, the Northern Hemisphere atmosphere loses energy, which is compensated by a northward cross-equatorial atmospheric energy transport, leading to a southward shift of the tropical precipitation in boreal fall. Thus, although Arctic vegetation is changed throughout the year, its effect on tropical precipitation exhibits substantial seasonal variations.
A Filter for Removing Sidelobe Artifacts in Bragg Scattering Layer (BSL) Analysis for S-Band Radar
Authors: Davison Jennifer L. 
Published: May 2015

AbstractThe local environment during the joint Atmospheric Radiation Measurement Program (ARM) Madden–Julian oscillation (MJO) Investigation Experiment (AMIE)–Cooperative Indian Ocean Experiment on Intraseasonal Variability in Year 2011 (CINDY2011)–Dynamics of the MJO (DYNAMO) field experiments caused frequent occurrences of sidelobe artifacts in the NCAR S-Pol radar dataset. Although generally low in radar reflectivity factor value (less than 5 dBZ), this contamination still proved problematic for Bragg scattering layer (BSL) analysis, generating numerous false BSL edge detections. In this paper, a statistical filtering technique is developed that effectively removes these false BSL edge detections, utilizing a new version of BSL analysis based on range–height indicator (RHI) data instead of plan position indicator data.
The National Perinatal Depression Initiative: An evaluation of access to general practitioners, psychologists and psychiatrists through the Medicare Benefits Schedule
Authors: Chambers Georgina M , Randall Sean , Hoang Van Phuong , Sullivan Elizabeth A , Highet Nicole , Croft Maxine , Mihalopoulos Cathrine , Morgan Vera A , Reilly Nicole , Austin Marie-Paule 
Published: May 2015

Objective: To evaluate the impact of the National Perinatal Depression Initiative on access to Medicare services for women at risk of perinatal mental illness. Method: Retrospective cohort study using difference-in-difference analytical methods to quantify the impact of the National Perinatal Depression Initiative policies on Medicare Benefits Schedule mental health usage by Australian women giving birth between 2006 and 2010. A random sample of women of reproductive age enrolled in Medicare who had not given birth where used as controls. The main outcome measures were the proportions of women giving birth each month who accessed a Medicare Benefits Schedule mental health items during the perinatal period (pregnancy through to the end of the first postnatal year) before and after the introduction of the National Perinatal Depression Initiative. Results: The proportion of women giving birth who accessed at least one mental health item during the perinatal period increased from 88 to 141 per 1000 between 2007 and 2010. The difference-in-difference analysis showed that while there was an overall increase in Medicare Benefits Schedule mental health item access as a result of the National Perinatal Depression Initiative, this did not reach statistical significance. However, the National Perinatal Depression Initiative was found to significantly increase access in subpopulations of women, particularly those aged under 25 and over 34 years living in major cities. Conclusion: In the 2 years following its introduction, the National Perinatal Depression Initiative was found to have increased access to Medicare funded mental health services in particular groups of women. However, an overall increase across all groups did not reach statistical significance. Further studies are needed to assess the impact of the National Perinatal Depression Initiative on women during childbearing years, including access to tertiary care, the cost-effectiveness of the initiative, and mental health outcomes. It is recommended that new mental health policy initiatives incorporate a planned strategic approach to evaluation, which includes sufficient follow-up to assess the impact of public health strategies.
The thalamus as a putative biomarker in neurodegenerative disorders
Authors: Power Brian D , Looi Jeffrey CL 
Published: May 2015

Objective: This review provides a brief account of the clinically relevant functional neuroanatomy of the thalamus, before considering the utility of various modalities utilized to image the thalamus and technical challenges therein, and going on to provide an overview of studies utilizing structural imaging techniques to map thalamic morphology in the spectrum of neurodegenerative disorders. Methods: A systematic search was conducted for peer-reviewed studies involving structural neuroimaging modalities investigating the morphology (shape and/or size) of the thalamus in the spectrum of neurodegenerative disorders. Results: While the precise role of the thalamus in the healthy brain remains unclear, there is a large body of knowledge accumulating which defines more precisely its functional connectivity within the connectome, and a burgeoning literature implicating its involvement in neurodegenerative disorders. It is proposed that correlation of clinical features with thalamic morphology (as a component of a quantifiable subcortical connectome) will provide a better understanding of neuropsychiatric dysfunction in various neurodegenerative disorders, potentially yielding clinically useful endophenotypes and disease biomarkers. Conclusion: Thalamic biomarkers in the neurodegenerative disorders have great potential to provide clinically meaningful knowledge regarding not only disease onset and progression but may yield targets of and perhaps a way of gauging response to future disease-modifying modalities.
Video-games used in a group setting is feasible and effective to improve indicators of physical activity in individuals with chronic stroke: a randomized controlled trial
Authors: Givon Noa , Zeilig Gabi , Weingarden Harold , Rand Debbie 
Published: May 2015

Objectives: To investigate the feasibility of using video-games in a group setting and to compare the effectiveness of video-games as a group intervention to a traditional group intervention for improving physical activity in individuals with chronic stroke. Design: A single-blind randomized controlled trial with evaluations pre and post a 3-month intervention, and at 3-month follow-up. Compliance (session attendance), satisfaction and adverse effects were feasibility measures. Grip strength and gait speed were measures of physical activity. Hip accelerometers quantified steps/day and the Action Research Arm Test assessed the functional ability of the upper extremity. Results: Forty-seven community-dwelling individuals with chronic stroke (29-78 years) were randomly allocated to receive video-game ( N=24) or traditional therapy ( N=23) in a group setting. There was high treatment compliance for both interventions (video-games-78%, traditional therapy-66%), but satisfaction was rated higher for the video-game (93%) than the traditional therapy (71%) (χ2=4.98, P=0.026). Adverse effects were not reported in either group. Significant improvements were demonstrated in both groups for gait speed (F=3.9, P=0.02), grip strength of the weaker (F=6.67, P=0.002) and stronger hands (F=7.5, P=0.001). Daily steps and functional ability of the weaker hand did not increase in either group. Conclusions: Using video-games in a small group setting is feasible, safe and satisfying. Video-games improve indicators of physical activity of individuals with chronic stroke.
Comparison of shock wave therapy and nutraceutical composed of Echinacea angustifolia, alpha lipoic acid, conjugated linoleic acid and quercetin (perinerv) in patients with carpal tunnel syndrome
Authors: Notarnicola Angela , Maccagnano Giuseppe , Tafuri Silvio , Fiore Alessandra , Pesce Vito , Moretti Biagio 
Published: May 2015

Even though the initial treatment of carpal tunnel syndrome (CTS) is conservative, knowledge of the clinical effects of supplements and of some methods of physiotherapy is still preliminary. Many biological mechanisms can support the administration of shock wave therapy (ESWT) or of alpha lipoic acid (ALA) based nutraceutical, conjugated linoleic acid (GLA), anti-oxidants and Echinacea angustifolia for CTS. The shock waves reduce the nerve compression, produce an anti-inflammatory action, and accelerate the regeneration of neuropathy. ALA and GLA induce antioxidant protective actions, reduce inflammation, promote neuroregeneration, and decrease pain. The Echinacea modulates the endogenous cannabinoid system. The aim of study is to verify the efficiency of shock wave therapy versus nutraceutical composed of ALA, GLA, and Echinacea in CTS. Sixty patients were enrolled in this study and they were randomly assigned to one of two treatments. Both groups showed significant improvements in pain, symptoms’ severity and functional scores, and electrodiagnostic results until the sixth month. We verified a trend to a better pain regression in the nutraceutical group. The presence of the medicinal Echinacea represents an added value to the antioxidant effect in ALA and GLA, which can justify this result. ESWT or the association of ALA, GLA, and Echinacea proved to be two effective treatments for controlling symptoms and improving the evolution of CTS.