bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements in force variability and structure from vision- to memory-guided submaximal isometric knee extension in subacute stroke
Authors: Chow John W. , Stokic Dobrivoje S. 
Published: November 2017

We examined changes in variability, accuracy, frequency composition, and temporal regularity of force signal from vision-guided to memory-guided force-matching tasks in 17 subacute stroke and 17 age-matched healthy subjects. Subjects performed a unilateral isometric knee extension at 10, 30, and 50% of peak torque [maximum voluntary contraction (MVC)] for 10 s (3 trials each). Visual feedback was removed at the 5-s mark in the first two trials (feedback withdrawal), and 30 s after the second trial the subjects were asked to produce the target force without visual feedback (force recall). The coefficient of variation and constant error were used to quantify force variability and accuracy. Force structure was assessed by the median frequency, relative spectral power in the 0–3-Hz band, and sample entropy of the force signal. At 10% MVC, the force signal in subacute stroke subjects became steadier, more broadband, and temporally more irregular after the withdrawal of visual feedback, with progressively larger error at higher contraction levels. Also, the lack of modulation in the spectral frequency at higher force levels with visual feedback persisted in both the withdrawal and recall conditions. In terms of changes from the visual feedback condition, the feedback withdrawal produced a greater difference between the paretic, nonparetic, and control legs than the force recall. The overall results suggest improvements in force variability and structure from vision- to memory-guided force control in subacute stroke despite decreased accuracy. Different sensory-motor memory retrieval mechanisms seem to be involved in the feedback withdrawal and force recall conditions, which deserves further study.NEW & NOTEWORTHY We demonstrate that in the subacute phase of stroke, force signals during a low-level isometric knee extension become steadier, more broadband in spectral power, and more complex after removal of visual feedback. Larger force errors are produced when recalling target forces than immediately after withdrawing visual feedback. Although visual feedback offers better accuracy, it worsens force variability and structure in subacute stroke. The feedback withdrawal and force recall conditions seem to involve different memory retrieval mechanisms.
Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities
Authors: Waitkus Matthew S. , Pirozzi Christopher J. , Moure Casey J. , Diplas Bill H. , Hansen Landon J. , Carpenter Austin B. , Yang Rui , Wang Zhaohui , Ingram Brian O. , Karoly Edward D. , Mohney Robert P. , Spasojevic Ivan , McLendon Roger E. , Friedman Henry S. , He Yiping , Bigner Darell D. , Yan Hai 
Published: November 2017

Abstract
Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1R132H-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1R132H-induced metabolic alterations and promoting IDH1R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its nonredundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1R132H-mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations.
Significance: These findings show that the homonid-specific brain enzyme GDH2 may be essential to mitigate metabolic liabilities created by IDH1 mutations in glioma, with possible implications to leverage its therapeutic management by IDH1 inhibitors. Cancer Res; 78(1); 36–50. ©2017 AACR.
Understanding Mitochondrial Polymorphisms in Cancer
Authors: Bussard Karen M. , Siracusa Linda D. 
Published: November 2017

AbstractAlterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 6051–9. ©2017 AACR.
Uncoupling the Oncogenic Engine
Authors: Schambach Axel , Schott Juliane W. , Morgan Michael A. 
Published: November 2017

Abstract
Inhibition of oncogenic signaling and correction of aberrant metabolic processes may be key paradigms to eliminate cancer cells. The high incidence of activating RAS mutations and hyperactivated ERK1/2 signaling observed in many human tumors and the lack of effective targeted therapies to elicit long-term inhibition of the RAS-ERK1/2 signaling pathway add to the importance of discovering novel strategies to treat malignancies characterized by elevated RAS-ERK1/2 signaling. In this review, we describe connections between oncogenic signaling and cancer cell metabolism and how these links may be exploited for novel modern molecular medicine approaches. Cancer Res; 77(22); 6060–4. ©2017 AACR.
RAZOR: A Phase II Open Randomized Trial of Screening Plus Goserelin and Raloxifene Versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer
Authors: Howell Anthony , Ashcroft Linda , Fallowfield Lesley , Eccles Diana M. , Eeles Rosalind A. , Ward Ann , Brentnall Adam R. , Dowsett Mitchell , Cuzick Jack M. , Greenhalgh Rosemary , Boggis Caroline , Motion Jamie , Sergeant Jamie C. , Adams Judith , Evans D. Gareth 
Published: November 2017

Abstract
Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention.
Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density.
Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period.
Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed.
Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58–66. ©2017 AACR.
Diabetes and Overall Survival among Breast Cancer Patients in the U.S. Military Health System
Authors: Shao Stephanie , Gill Abegail A. , Zahm Shelia H. , Jatoi Ismail , Shriver Craig D. , McGlynn Katherine A. , Zhu Kangmin 
Published: November 2017

Abstract
Background: Although research suggests that type II diabetes mellitus (DM-2) is associated with overall and breast cancer–specific decreased survival, most prior studies of breast cancer survival investigated the effect of preexisting DM-2 without assessing the effect of DM-2 diagnosed at or after breast cancer diagnosis. This study examined the relationship between DM-2 diagnosed before and after breast cancer diagnosis and overall survival.
Methods: This study uses linked Department of Defense cancer registry and medical claims data from 9,398 women diagnosed with breast cancer between 1998 and 2007. Cox proportional hazards models were used to assess the association between DM-2 and overall survival.
Results: Our analyses showed that women with DM-2 diagnosed before breast cancer diagnosis tended to have a higher risk of mortality compared with women without diabetes [HR = 1.17; 95% confidence interval (CI), 0.95–1.44] after adjustment for potential confounders. Similarly, patients diagnosed with DM-2 at or after breast cancer diagnosis had increased mortality compared with women without DM-2 (HR = 1.39; 95% CI, 1.16–1.66). The similar tendency was also observed among most subgroups when results were stratified by race, menopausal status, obesity, tumor hormone receptor status, and stage.
Conclusions: Using data from a health system that provides universal health care to its beneficiaries, this study showed an increased risk of death associated with DM-2, regardless of whether it was diagnosed before or at/after breast cancer diagnosis.
Impact: These results suggest the potential effects of factors independent of the timing of DM-2 clinical diagnosis on the association of DM-2 with overall survival. Cancer Epidemiol Biomarkers Prev; 27(1); 50–57. ©2017 AACR.
Trapping Cancers as They Adapt to Survive
Authors: Haq Rizwan 
Published: November 2017

Abstract
Summary: The evolution of cancer cells limits the efficacy of nearly all treatments for patients with solid tumors. Characterizing how cancers adapt to treatment could therefore lead to approaches that overcome resistance to therapy. In this issue of Cancer Discovery, Song and colleagues describe the evolution of melanomas upon exposure to BRAF inhibitors, demonstrating that adaptive changes in the tumor create a vulnerability that can be targeted with immune checkpoint inhibitors. Cancer Discov; 7(11); 1216–7. ©2017 AACR.
See related article by Song et al., p. 1248.
Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets
Authors: Chen Wenchun , Druzak Samuel A. , Wang Yingchun , Josephson Cassandra D. , Hoffmeister Karin M. , Ware Jerry , Li Renhao 
Published: November 2017

Objective—
Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared on transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed.

Approach and Results—

Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration, the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF
−
/
−
plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca
2+
, phosphatidylserine exposure, and desialylation of platelets, which were absent in VWF
−/−
platelets or inhibited by OS1, which is a monomeric 11-residue peptide (CTERMALHNLC). Furthermore, refrigerated VWF
−/−
platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival.

Conclusions—
Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF–GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.
Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support
Authors: Saeed Omar , Rangasamy Sabarivinoth , Selevany Ibrahim , Madan Shivank , Fertel Jeremy , Eisenberg Ruth , Aljoudi Mohammad , Patel Snehal R. , Shin Julia , Sims Daniel B. , Reyes Gil Morayma , Goldstein Daniel J. , Slepian Marvin J. , Billett Henny H. , Jorde Ulrich P. 
Published: November 2017

Background:
Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.

Methods and Results:

A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5–50;
P
<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2–16.1;
P
=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL,
P
<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (
P
<0.001).

Conclusions:
Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.
Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study
Authors: Minami Yoshiyasu , Wang Zhao , Aguirre Aaron D. , Ong Daniel S. , Kim Chong‐Jin , Uemura Shiro , Soeda Tsunenari , Lee Hang , Fujimoto James , Jang Ik‐Kyung 
Published: November 2017

Background
Previous studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin‐cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease.

Methods and Results

A total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin‐cap area (fibrous cap thickness, <200 μm) was measured using a novel 3‐dimensional computer‐aided algorithm. Overall, the thin‐cap area significantly decreased from baseline (median, 2.852 mm
2
; 25
th
–75
th
percentile, 1.023–6.157 mm
2
) to follow‐up (median, 1.210 mm
2
; 25
th
–75
th
percentile, 0.250–3.192 mm
2
;
P
<0.001), and low‐density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow‐up (mean±SD, 76.3±23.3 mg/dL;
P
<0.001). The general linear model with multiple predictor variables revealed that the thin‐cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm
2
; 95% confidence interval, 0.350–3.033 mm
2
;
P
=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, −1.535 mm
2
; 95% confidence interval, −2.561 to −0.509 mm
2
;
P
=0.003).

Conclusions
Chronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01110538.
A Model for State Divisions of the Asta National Solo Competition
Authors: Fried Eric 
Published: November 2017

My first experience as chair of the Texas division of the ASTA National Solo Competition came late in the summer of 2006 when the former chair accepted another teaching position outside of the state. Taking over at the last minute forced me to organize hurriedly, and I was most thankful for the assistance given me by the outgoing chair, the state president, and the board. After the competition was over, our board suggested that I consider organizing our policies and procedures into a state competition guideline handbook so future competition chairs would not have to “reinvent the wheel.” This article will address the processes, concerns, and the options available in organizing and bringing to fruition this important and prestigious event and provide guidelines for creating competition handbooks that are appropriate to each state. State competition chairs for ASTA's National Solo Competition are met with expected and often surprising challenges, and may feel that they are “flying by the seat of their pants” when dealing with myriad issues that arise when organizing their state events. While each state has issues that make them unique, planning well in advance of the event makes for a smoother and less stressful competition for the chair, the state board, adjudicators, and the competitors.
Adam Smith on the Philosophy and Provision of Education
Authors: Thomas Alex M. 
Published: November 2017

This article examines the views of Adam Smith on the philosophy and provision of education. On the basis of his Theory of Moral Sentiments and other writings, it becomes clear that Smith views education, conceived broadly to include both the learning of ‘wisdom’ and ‘moral sentiments’, as central to a prosperous or flourishing society. Education, in Smith’s view, is not restricted to formal institutions of education but also includes social learning—that between parents and children, and the learning arising from friendships. For Smith, education is a social process. Smith also discusses the important role of wonder and surprise in the process of education. The provision of education, as outlined in his Wealth of Nations, largely supports the public provision of education with partial contributions from the enrolled students. Smith favoured education for all because he believed that it would offset the harmful effects of division of labour on the workers, and therefore, education had to be accessible to the workers. The essay concludes by reiterating Smith’s position that education for all is necessary to create a prosperous society. JEL: A20, B12, B31
Peripapillary retinal nerve fibre layer as measured by optical coherence tomography is a prognostic biomarker not only for physical but also for cognitive disability progression in multiple sclerosis
Authors: Bsteh Gabriel , Hegen Harald , Teuchner Barbara , Amprosi Matthias , Berek Klaus , Ladstätter Felix , Wurth Sebastian , Auer Michael , Di Pauli Franziska , Deisenhammer Florian , Berger Thomas 
Published: November 2017

Background: Peripapillary retinal nerve fibre layer (pRNFL) thickness is emerging as a marker of axonal degeneration in multiple sclerosis (MS). Objective: We aimed to prospectively assess the predictive value of pRNFL for progression of physical and cognitive disability in relapsing-remitting MS (RRMS). Methods: In this 3-year longitudinal study on 151 RRMS patients, pRNFL was measured by spectral-domain optical coherence tomography (OCT). We used proportional hazard models, correcting for age, sex, disease duration, Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) at baseline, to test a pRNFL thickness ≤88 µm at baseline for prediction of EDSS progression and cognitive decline. We also evaluated the decrease in pRNFL thickness from baseline to year 3 in a multivariate linear regression model. Results: pRNFL thickness ≤88 µm was independently associated with a threefold increased risk of EDSS progression ( p < 0.001) and a 2.7-fold increased risk of cognitive decline within the subsequent 3 years ( p < 0.001). Mean pRNFL delta was −5.3 µm (SD, 4.2). It was significantly negatively impacted by EDSS progression, cognitive decline, higher age and disease duration, while positively impacted by disease-modifying therapy (DMT). Conclusion: Cross-sectional and longitudinal monitoring of pRNFL is useful as a biomarker for prediction of physical and cognitive disability progression in patients with RRMS in everyday clinical practice.