bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Gaudin model of type G2
Authors: Lu Kang , Mukhin Evgeny 
Published: February 2018

We derive a number of results related to the Gaudin model associated to the simple Lie algebra of type G2. We compute explicit formulas for solutions of the Bethe ansatz equations associated to the tensor product of an arbitrary finite-dimensional irreducible module and the vector representation. We use this result to show that the Bethe ansatz is complete in any tensor product where all but one factor are vector representations and the evaluation parameters are generic. We show that the points of the spectrum of the Gaudin model in type G2 are in a bijective correspondence with self-self-dual spaces of polynomials. We study the set of all self-self-dual spaces — the self-self-dual Grassmannian. We establish a stratification of the self-self-dual Grassmannian with the strata labeled by unordered sets of dominant integral weights and unordered sets of nonnegative integers, satisfying certain explicit conditions. We describe closures of the strata in terms of representation theory.
Decision systems in rough set theory: A set operatorial perspective
Authors: Chiaselotti G. , Gentile T. , Infusino F. 
Published: February 2018

In rough set theory (RST), the notion of decision table plays a fundamental role. In this paper, we develop a purely mathematical investigation of this notion to show that several basic aspects of RST can be of interest also for mathematicians who work with algebraic and discrete methods.In this abstract perspective, we call decision system a sextuple [Formula: see text] [Formula: see text], where [Formula: see text], [Formula: see text], [Formula: see text] are non-empty sets whose elements are called, respectively, objects, condition attributes, values, [Formula: see text] is a (possibly empty) set whose elements are called decision attributes, [Formula: see text] and [Formula: see text] is a map.The basic tool of our analysis is the equivalence relation [Formula: see text] on [Formula: see text], depending on the choice of a condition attribute subset [Formula: see text] and defined as follows: [Formula: see text] We denote by [Formula: see text] the equivalence class of [Formula: see text] with respect to [Formula: see text]. We interpret the classical RST notions of consistency and inconsistency for a decision table in an abstract algebraic set operatorial perspective and, in such a context, we introduce and investigate a kind of local consistency in any decision system [Formula: see text]. More specifically, we fix [Formula: see text], [Formula: see text] and try to determine in what cases all objects [Formula: see text] satisfy the condition [Formula: see text]. Then, we build a formal general framework whose basic tools are two local consistency set operators and a global closure operator, the condition attribute set [Formula: see text]. This paper provides a detailed study of these set operators, of the induced set systems and of the most relevant links between them.
NRAS-Mutated Rhabdomyosarcoma Cells Are Vulnerable to Mitochondrial Apoptosis Induced by Coinhibition of MEK and PI3Kα
Authors: Dolgikh Nadezda , Hugle Manuela , Vogler Meike , Fulda Simone 
Published: February 2018

AbstractSequencing studies have revealed recurrent mutations in the RAS pathway in rhabdomyosarcoma (RMS). However, RAS effector pathways in RMS are poorly defined. Here, we report that coinhibition of NRAS or MEK plus PI3Kα triggers widespread apoptosis in NRAS-mutated RMS cells. Subtoxic concentrations of the MEK inhibitor MEK162 and the PI3Kα-specific inhibitor BYL719 synergized to trigger apoptosis in NRAS-mutated RMS cells in vitro and in vivo. NRAS- or HRAS-mutated cell lines were more vulnerable to MEK162/BYL719 cotreatment than RAS wild-type cell lines, and MEK162/BYL719 cotreatment was more effective to trigger apoptosis in NRAS-mutated than RAS wild-type RMS tumors in vivo. We identified BCL-2–modifying factor (BMF) as an inhibitory target of oncogenic NRAS, with either NRAS silencing or MEK inhibition upregulating BMF mRNA and protein levels, which BYL719 further increased. BMF silencing ablated MEK162/BYL719-induced apoptosis. Mechanistic investigations implicated a proapoptotic rebalancing of BCL-2 family members and suppression of cap-dependent translation in apoptotic sensitivity upon MEK162/BYL719 cotreatment. Our results offer a rationale for combining MEK- and PI3Kα-specific inhibitors in clinical treatment of RAS-mutated RMS.Significance: These findings offer a mechanistic rationale for combining MEK- and PI3Kα-specific inhibitors in the clinical treatment of RAS-mutated forms of often untreatable rhabdomyosarcomas. Cancer Res; 78(8); 2000–13. ©2018 AACR.
Nuclear Receptor LRH-1 Functions to Promote Castration-Resistant Growth of Prostate Cancer via Its Promotion of Intratumoral Androgen Biosynthesis
Authors: Xiao Lijia , Wang Yuliang , Xu Kexin , Hu Hao , Xu Zhenyu , Wu Dinglan , Wang Zhu , You Wenxing , Ng Chi-Fai , Yu Shan , Chan Franky Leung 
Published: February 2018

Abstract
Targeting of steroidogenic enzymes (e.g., abiraterone acetate targeting CYP17A1) has been developed as a novel therapeutic strategy against metastatic castration-resistant prostate cancer (CRPC). However, resistance to steroidal inhibitors inevitably develops in patients, the mechanisms of which remain largely unknown. Liver receptor homolog-1 (LRH-1, NR5A2) is a nuclear receptor, originally characterized as an important regulator of some liver-specific metabolic genes. Here, we report that LRH-1, which exhibited an increased expression pattern in high-grade prostate cancer and CRPC xenograft models, functions to promote de novo androgen biosynthesis via its direct transactivation of several key steroidogenic enzyme genes, elevating intratumoral androgen levels and reactivating AR signaling in CRPC xenografts as well as abiraterone-treated CRPC tumors. Pharmacologic inhibition of LRH-1 activity attenuated LRH-1–mediated androgen deprivation and anti-androgen resistance of prostate cancer cells. Our findings not only demonstrate the significant role of LRH-1 in the promotion of intratumoral androgen biosynthesis in CRPC via its direct transcriptional control of steroidogenesis, but also suggest targeting LRH-1 could be a potential therapeutic strategy for CRPC management.
Significance: These findings not only demonstrate the significant role of the nuclear receptor LRH-1 in the promotion of intratumoral androgen biosynthesis in CRPC via its direct transcriptional control of steroidogenesis, but also suggest targeting LRH-1 could be a potential therapeutic strategy for CRPC management. Cancer Res; 78(9); 2205–18. ©2018 AACR.
SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways
Authors: Zhang Yan-Li , Li Qing , Yang Xiao-Mei , Fang Fang , Li Jun , Wang Ya-Hui , Yang Qin , Zhu Lei , Nie Hui-Zhen , Zhang Xue-Li , Feng Ming-Xuan , Jiang Shu-Heng , Tian Guang-Ang , Hu Li-Peng , Lee Ho-Young , Lee Su-Jae , Xia Qiang , Zhang Zhi-Gang 
Published: February 2018

Abstract
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.
Significance: Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. Cancer Res; 78(9); 2305–17. ©2018 AACR.
Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials
Authors: Chen Yu-Pei , Tang Ling-Long , Yang Qi , Poh Sharon-Shuxian , Hui Edwin P. , Chan Anthony T.C. , Ong Whee-Sze , Tan Terence , Wee Joseph , Li Wen-Fei , Chen Lei , Ma Brigette B.Y. , Tong Macy , Tan Sze-Huey , Cheah Shie-Lee , Fong Kam-Weng , Sommat Kiattisa , Soong Yoke Lim , Guo Ying , Lin Ai-Hua , Sun Ying , Hong Ming-Huang , Cao Su-Mei , Chen Ming-Yuan , Ma Jun 
Published: February 2018

Abstract
Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC.
Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.
Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56–0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51–0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48–1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected.
Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824–33. ©2018 AACR.
Identification of Novel Pathways of Osimertinib Disposition and Potential Implications for the Outcome of Lung Cancer Therapy
Authors: MacLeod A. Kenneth , Lin De , Huang Jeffrey T.–J. , McLaughlin Lesley A. , Henderson Colin J. , Wolf C. Roland 
Published: February 2018

Abstract
Purpose: Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor used in treatment of non–small cell lung cancer. A full understanding of its disposition and capacity for interaction with other medications will facilitate its effective use as a single agent and in combination therapy.
Experimental Design: Recombinant cytochrome P450s and liver microsomal preparations were used to identify novel pathways of osimertinib metabolism in vitro. A panel of knockout and mouse lines humanized for pathways of drug metabolism were used to establish the relevance of these pathways in vivo.
Results: Although some osimertinib metabolites were similar in mouse and human liver samples there were several significant differences, in particular a marked species difference in the P450s involved. The murine Cyp2d gene cluster played a predominant role in mouse, whereas CYP3A4 was the major human enzyme responsible for osimertinib metabolism. Induction of this enzyme in CYP3A4 humanized mice substantially decreased circulating osimertinib exposure. Importantly, we discovered a further novel pathway of osimertinib disposition involving CPY1A1. Modulation of CYP1A1/CYP1A2 levels markedly reduced parent drug concentrations, significantly altering metabolite pharmacokinetics (PK) in humanized mice in vivo.
Conclusions: We demonstrate that a P450 enzyme expressed in smokers' lungs and lung tumors has the capacity to metabolise osimertinib. This could be a significant factor in defining the outcome of osimertinib treatment. This work also illustrates how P450-humanized mice can be used to identify and mitigate species differences in drug metabolism and thereby model the in vivo effect of critical metabolic pathways on anti-tumor response. Clin Cancer Res; 24(9); 2138–47. ©2018 AACR.
Natural History of Vertebrobasilar Dolichoectatic and Fusiform Aneurysms: A Systematic Review and Meta-Analysis
Authors: Nasr Deena M. , Flemming Kelly D. , Lanzino Giuseppe , Cloft Harry J. , Kallmes David F. , Murad Mohammad Hassan , Brinjikji Waleed 
Published: February 2018

<b><i>Background and Purpose:</i></b> Vertebrobasilar non-saccular and dolichoectatic aneurysms (VBDA) are a rare type of aneurysm and are generally associated with poor prognosis. In order to better characterize the natural history of VBDAs, we performed a systematic review and meta-analysis of the literature to determine rates of mortality, growth, rupture, ischemia, and intraparenchymal hemorrhage. <b><i>Materials and Methods:</i></b> We searched the literature for longitudinal natural history studies of VBDA patients reporting clinical and imaging outcomes. Studied outcomes included annualized rates of growth, rupture, ischemic stroke, intracerebral hemorrhage (ICH), and mortality. We also studied the association between aneurysm morphology (dolichoectatic versus fusiform) and natural history. Meta-analysis was performed using a random-effects model using summary statistics from included studies. <b><i>Results:</i></b> Fifteen studies with 827 patients and 5,093 patient-years were included. The overall annual mortality rate among patients with VBDAs was 13%/year (95% CI 8–19). Patients with fusiform aneurysms had a higher mortality rate than those with dolichoectatic aneurysms, but this did not reach statistical significance (12 vs. 8%, <i>p</i> = 0.11). The overall growth rate was 6%/year (95% CI 4–13). Patients with fusiform aneurysms had higher growth rates than those with dolichoectatic aneurysms (12 vs. 3%, <i>p</i> &#x3c; 0.0001). The overall rupture rate was 3%/year (95% CI 1–5). Patients with fusiform aneurysms had higher rupture rates than those with dolichoectatic aneurysms (3 vs. 0%, <i>p</i> &#x3c; 0.0001). The overall rate of ischemic stroke was 6%/year (95% CI 4–9). Patients with dolichoectatic aneurysms had higher ischemic stroke rates than those with fusiform aneurysms, but this did not reach statistical significance (8 vs. 4%, <i>p</i> = 0.13). The overall rate of ICH was 2%/year (95% CI 0–8) with no difference in rates between dolichoectatic and fusiform aneurysms (2 vs. 2%, <i>p</i> = 0.65). <b><i>Conclusion:</i></b> In general, the natural history of ­VBDAs is poor. However, dolichoectatic and fusiform ­VBDAs appear to have distinct natural histories with substantially higher growth and rupture associated with fusiform aneurysms. These findings suggest that these aneurysms should be considered separate entities. Further studies on the natural history of vertebrobasilar dolichoectatic and fusiform aneurysms with more complete follow-up are needed to better understand the risk factors for progression of these aneurysms.
Low Cerebral Oxygenation Is Associated with Cognitive Impairment in Chronic Hemodialysis Patients
Authors: Kovarova Lucie , Valerianova Anna , Kmentova Tereza , Lachmanova Jana , Hladinova Zuzana , Malik Jan 
Published: February 2018

<b><i>Background/Aims:</i></b> High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. <b><i>Methods:</i></b> Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired <i>t</i> test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score &#x3c;26). Multiple linear regression analysis was used to adjust for principal confounders. <b><i>Results:</i></b> Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, <i>p</i> = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, <i>p</i> = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, <i>p</i> &#x3c; 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (<i>p</i> = 0.007). <b><i>Conclusion:</i></b> Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.
Anxiety After Stroke
Authors: Chun Ho-Yan Yvonne , Whiteley William N. , Dennis Martin S. , Mead Gillian E. , Carson Alan J. 
Published: February 2018

Background and Purpose—
Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack.

Methods—
We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale.

Results—

Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45–0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94–9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3–5, [anxiety] 55% versus [no anxiety] 29%;
P
<0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10–27 versus [no anxiety] 0, 0–5;
P
<0.001).

Conclusions—
Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety.
Clinical and Demographic Characteristics Associated With Suboptimal Primary Stroke and Transient Ischemic Attack Prevention
Authors: Turner Grace M. , Calvert Melanie , Feltham Max G. , Ryan Ronan , Finnikin Samuel , Marshall Tom 
Published: February 2018

Background and Purpose—
Primary prevention of stroke and transient ischemic attack (TIA) is important to reduce the burden of these conditions; however, prescribing of prevention drugs is suboptimal. We aimed to identify individual clinical and demographic characteristics associated with potential missed opportunities for prevention therapy with lipid-lowering, anticoagulant, or antihypertensive drugs before stroke/TIA.

Methods—
We analyzed anonymized electronic primary care records from a UK primary care database that covers 561 family practices. Patients with first-ever stroke/TIA, ≥18 years, with diagnosis between January 1, 2009, and December 31, 2013, were included. Missed opportunities for prevention were defined as people with clinical indications for lipid-lowering, anticoagulant, or antihypertensive drugs but not prescribed these drugs before their stroke/TIA. Mixed-effect logistic regression models evaluated the relationship between missed opportunities and individual clinical/demographic characteristics.

Results—
The inclusion criteria were met by 29 043 people with stroke/TIA. Patients with coronary heart disease, chronic kidney disease, peripheral arterial disease, or diabetes mellitus were at less risk of a missed opportunity for prescription of lipid-lowering and antihypertensive drugs. However, patients with a 10-year cardiovascular disease risk ≥20% but without these diagnoses had increased risk of having a missed opportunity for prescription of lipid-lowering drugs or antihypertensive drugs. Women were less likely to be prescribed anticoagulants but more likely to be prescribed antihypertensive drugs. The elderly (≥85 years of age) were less likely to be prescribed all 3 prevention drugs, compared with people aged 75 to 79 years.

Conclusions—
Knowing the patient characteristics predictive of missed opportunities for stroke prevention may help primary care identify and appropriately manage these patients. Improving the management of these groups may reduce their risk and potentially prevent large number of future strokes and TIAs in the population.
Basil of Caesarea’s Authorship of Epistle 361 and His Relationship with the Homoiousians Reconsidered
Authors: Giulea Dragoş Andrei 
Published: February 2018

Abstract
A comparative analysis of Ep. 361 and Eun. 1.19 in terms of language and ideas will offer a renewed confirmation (on internal grounds) of Basil of Caesarea’s authorship of Ep. 361 and a new perspective on Basil’s relationship with the Homoiousians. In addition, the article will also retrace the steps and revisit the purpose of Basil’s argument. Thus we discover in the early Basil an author simultaneously receptive to both Homoiousian and pro-Nicene visions, but leaning towards an improved Homoiousian solution. The article further investigates Basil’s vision of ousia in Ep. 361 and finds that—unlike in his later, mature, period—the early Basil shares with the Homoiousians and Eusebius of Caesarea two doctrinal elements, namely the understanding of ousia as individual substance and an associated theology of “likeness”. He inherits this view from a tradition originating in the third century, which received its official confirmation at the council of Antioch in 268. This vision is also present in the first part of Basil’s Contra Eunomium. Instead of considering Basil as a Homoiousian, one may see him, together with Eusebius and the Homoiousians, as a representative of the Antiochene legacy.