bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collateral flow as causative of good outcomes in endovascular stroke therapy
Authors: Sheth Sunil A , Sanossian Nerses , Hao Qing , Starkman Sidney , Ali Latisha K , Kim Doojin , Gonzalez Nestor R , Tateshima Satoshi , Jahan Reza , Duckwiler Gary R , Saver Jeffrey L , Vinuela Fernando , Liebeskind David S ,   for the UCLA Collateral Investigators
Published: November 2014

BackgroundEndovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome.MethodsDemographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010.ResultsHigher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival.ConclusionsImproved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome.
Lattices of regular closed subsets of closure spaces
Authors: Santocanale Luigi , Wehrung Friedrich 
Published: November 2014

For a closure space (P, φ) with φ(ø) = ø, the closures of open subsets of P, called the regular closed subsets, form an ortholattice Reg (P, φ), extending the poset Clop (P, φ) of all clopen subsets. If (P, φ) is a finite convex geometry, then Reg (P, φ) is pseudocomplemented. The Dedekind–MacNeille completion of the poset of regions of any central hyperplane arrangement can be obtained in this way, hence it is pseudocomplemented. The lattice Reg (P, φ) carries a particularly interesting structure for special types of convex geometries, that we call closure spaces of semilattice type. For finite such closure spaces,• Reg (P, φ) satisfies an infinite collection of stronger and stronger quasi-identities, weaker than both meet- and join-semidistributivity. Nevertheless it may fail semidistributivity.• If Reg (P, φ) is semidistributive, then it is a bounded homomorphic image of a free lattice.• Clop (P, φ) is a lattice if and only if every regular closed set is clopen.The extended permutohedron R (G) on a graph G and the extended permutohedron Reg S on a join-semilattice S, are both defined as lattices of regular closed sets of suitable closure spaces. While the lattice of all regular closed sets is, in the semilattice context, always the Dedekind–MacNeille completion of the poset of clopen sets, this does not always hold in the graph context, although it always does so for finite block graphs and for cycles. Furthermore, both R (G) and Reg S are bounded homomorphic images of free lattices.
Myeloid Expression of Adenosine A2A Receptor Suppresses T and NK Cell Responses in the Solid Tumor Microenvironment
Authors: Cekic Caglar , Day Yuan-Ji , Sag Duygu , Linden Joel 
Published: November 2014

Abstract
High concentrations of adenosine in tumor microenvironments inhibit antitumor cytotoxic lymphocyte responses. Although T cells express inhibitory adenosine A2A receptors (A2AR) that suppress their activation and inhibit immune killing of tumors, a role for myeloid cell A2ARs in suppressing the immune response to tumors has yet to be investigated. In this study, we show that the growth of transplanted syngeneic B16F10 melanoma or Lewis lung carcinoma cells is slowed in Adora2af/f–LysMCre+/− mice, which selectively lack myeloid A2ARs. Reduced melanoma growth is associated with significant increases in MHCII and IL12 expression in tumor-associated macrophages and with &gt;90% reductions in IL10 expression in tumor-associated macrophages, dendritic cells (DC), and Ly6C+ or Ly6G+ myeloid-derived suppressor cells (MDSC). Myeloid deletion of A2ARs significantly increases CD44 expression on tumor-associated T cells and natural killer (NK) cells. Depletion of CD8+ T cells or NK cells in tumor-bearing mice indicates that both cell types initially contribute to slowing melanoma growth in mice lacking myeloid A2A receptors, but tumor suppression mediated by CD8+ T cells is more persistent. Myeloid-selective A2AR deletion significantly reduces lung metastasis of melanomas that express luciferase (for in vivo tracking) and ovalbumin (as a model antigen). Reduced metastasis is associated with increased numbers and activation of NK cells and antigen-specific CD8+ T cells in lung infiltrates. Overall, the findings indicate that myeloid cell A2ARs have direct myelosuppressive effects that indirectly contribute to the suppression of T cells and NK cells in primary and metastatic tumor microenvironments. The results indicate that tumor-associated myeloid cells, including macrophages, DCs, and MDSCs all express immunosuppressive A2ARs that are potential targets of adenosine receptor blockers to enhance immune killing of tumors. Cancer Res; 74(24); 7250–9. ©2014 AACR.
Mig-6 Suppresses Endometrial Cancer Associated with Pten Deficiency and ERK Activation
Authors: Kim Tae Hoon , Yoo Jung-Yoon , Kim Hong Im , Gilbert Jenifer , Ku Bon Jeong , Li Jane , Mills Gordon B. , Broaddus Russell R. , Lydon John P. , Lim Jeong Mook , Yoon Ho-Geun , Jeong Jae-Wook 
Published: November 2014

Abstract
PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate estrogen receptor α–dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice, where Mig-6 was overexpressed in progesterone receptor–expressing cells, exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PRcre/+Ptenf/f mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer. Cancer Res; 74(24); 7371–82. ©2014 AACR.
Mitochondrial MKP1 Is a Target for Therapy-Resistant HER2-Positive Breast Cancer Cells
Authors: Candas Demet , Lu Chung-Ling , Fan Ming , Chuang Frank Y.S. , Sweeney Colleen , Borowsky Alexander D. , Li Jian Jian 
Published: November 2014

Abstract
The MAPK phosphatase MKP1 (DUSP1) is overexpressed in many human cancers, including chemoresistant and radioresistant breast cancer cells, but its functional contributions in these settings are unclear. Here, we report that after cell irradiation, MKP1 translocates into mitochondria, where it prevents apoptotic induction by limiting accumulation of phosphorylated active forms of the stress kinase JNK. Increased levels of mitochondrial MKP1 after irradiation occurred in the mitochondrial inner membrane space. Notably, cell survival regulated by mitochondrial MKP1 was responsible for conferring radioresistance in HER2-overexpressing breast cancer cells, due to the fact that MKP1 serves as a major downstream effector in the HER2-activated RAF–MEK–ERK pathway. Clinically, we documented MKP1 expression exclusively in HER2-positive breast tumors, relative to normal adjacent tissue from the same patients. MKP1 overexpression was also detected in irradiated HER2-positive breast cancer stem-like cells (HER2+/CD44+/CD24−/low) isolated from a radioresistant breast cancer cell population after long-term radiation treatment. MKP1 silencing reduced clonogenic survival and enhanced radiosensitivity in these stem-like cells. Combined inhibition of MKP1 and HER2 enhanced cell killing in breast cancer. Together, our findings identify a new mechanism of resistance in breast tumors and reveal MKP1 as a novel therapeutic target for radiosensitization. Cancer Res; 74(24); 7498–509. ©2014 AACR.
Comparison of Uptake of Colorectal Cancer Screening Based on Fecal Immunochemical Testing (FIT) in Males and Females: A Systematic Review and Meta-analysis
Authors: Clarke Nicholas , Sharp Linda , Osborne Aoife , Kearney Patricia M. 
Published: November 2014

AbstractBackground: Colorectal cancer is the third most common cancer in males and the second in females worldwide. Incidence and mortality are higher in men than women. Colorectal cancer screening is effective in reducing mortality. Internationally, fecal immunochemical testing (FIT) is increasingly being recommended as the primary screening test. This systematic review and meta-analysis aimed to determine whether uptake of FIT screening differs between men than women.Methods: We searched PubMed and Embase for peer-reviewed articles published in English during 2000–2013 for randomized controlled trials (RCT) or observational studies of screening using FIT that quantified numbers invited and participating by gender. Meta-analysis was performed using a random effects model.Results: Six hundred and eighty-five citations were identified, 19 meeting the inclusion criteria. Random effects meta-analysis found male uptake was significantly lower than female uptake [odds ratio (OR), 0.84; 95% confidence interval (CI), 0.75–0.95; P &lt; 0.01]. This generally persisted throughout subgroup analysis of study design (RCTs vs. observational studies and study quality), screening organization (methods of invitation, number of samples, age range of screening, recommendations, and reminders), and setting.Conclusions: Meta analysis of FIT screening studies indicates significantly lower uptake among men.Impact: Further investigation is required into factors influencing acceptability and participation of FIT screening in both sexes. Cancer Epidemiol Biomarkers Prev; 24(1); 39–47. ©2014 AACR.
ΔNP63α Transcriptionally Activates Chemokine Receptor 4 (CXCR4) Expression to Regulate Breast Cancer Stem Cell Activity and Chemotaxis
Authors: DeCastro Andrew J. , Cherukuri Pratima , Balboni Amanda , DiRenzo James 
Published: November 2014

Abstract
ΔNP63α, the predominant TP63 isoform expressed in diverse epithelial tissues, including the mammary gland, is required for the preservation of stem cells and has been implicated in tumorigenesis and metastasis. Despite data characterizing ΔNP63α as a master regulator of stem cell activity, identification of the targets underlying these effects is incompletely understood. Recently, ΔNP63α was identified as a key regulator in the promotion of proinflammatory programs in squamous cell carcinoma of the head and neck. Inflammation has been implicated as a potent driver of cancer stem cell phenotypes and metastasis. In this study, we sought to identify novel targets of ΔNP63α that confer cancer stem cell and prometastatic properties. Data presented here identify the gene encoding the chemokine receptor 4 (CXCR4) as a transcriptional target of ΔNP63α. Our data indicate that ΔNP63α enhances CXCR4 expression in breast cancer cells via its binding at two regions within the CXCR4 promoter. The CXCR4 antagonist AMD3100 was used to demonstrate that the pro–stem cell activity of ΔNP63α is mediated through its regulation of CXCR4. Importantly, we show that ΔNP63α promotes the chemotaxis of breast cancer cells towards the CXCR4 ligand SDF1α, a process implicated in the trafficking of breast cancer cells to sites of metastasis. This study highlights CXCR4 as a previously unidentified target of ΔNP63α, which plays a significant role in mediating ΔNP63α-dependent stem cell activity and chemotaxis toward SDF1α. Our findings suggest that ΔNP63α regulation of CXCR4 may have strong implications in the regulation of cancer stem cells and metastasis. Mol Cancer Ther; 14(1); 225–35. ©2014 AACR.
The Protein Phosphatase 2A Inhibitor LB100 Sensitizes Ovarian Carcinoma Cells to Cisplatin-Mediated Cytotoxicity
Authors: Chang Ki-Eun , Wei Bih-Rong , Madigan James P. , Hall Matthew D. , Simpson R. Mark , Zhuang Zhengping , Gottesman Michael M. 
Published: November 2014

Abstract
Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3, OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling. In vivo studies were conducted in an intraperitoneal metastatic mouse model using SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and γH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly enhanced tumor growth inhibition and prevented disease progression after treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation. Mol Cancer Ther; 14(1); 90–100. ©2014 AACR.
Mechanisms and Clinical Significance of Adenosine-Induced Dormant Accessory Pathway Conduction After Catheter Ablation
Authors: Spotnitz Michelle D. , Markowitz Steven M. , Liu Christopher F. , Thomas George , Ip James E. , Liez Joshua , Lerman Bruce B. , Cheung Jim W. 
Published: November 2014

Background—
Adenosine can unmask dormant pulmonary vein conduction after isolation. The role of adenosine in uncovering dormant accessory pathway (AP) conduction after AP ablation is unknown.

Methods and Results—

We evaluated 109 consecutive patients (age, 41±28 years; 62 [57%] men) who were administered adenosine after successful AP ablation. Dormant AP conduction was defined as adenosine-induced recurrent AP conduction, as demonstrated by recurrent preexcitation or change in retrograde ventriculoatrial activation patterns. Dormant AP conduction was identified in 13 (12%) patients. Adenosine led to transient retrograde AP conduction in 6 patients and transient anterograde AP conduction in 8 patients. In all these cases, adenosine-induced AP conduction occurred during the bradycardia phase of adenosine effect and resulted in dormant AP conduction times shorter than atrioventricular nodal conduction times before adenosine administration. On the basis of analysis of timing of occurrence of dormant AP conduction, the mechanism of adenosine-induced AP conduction was determined to be caused by AP excitability recovery in ≥12 (92%) cases. The presence of dormant AP conduction was a significant predictor of chronic recurrent AP conduction requiring repeat ablation (odds ratio, 8.54; 95% confidence interval, 1.09–66.9;
P
=0.041).

Conclusions—
Adenosine can unmask dormant AP conduction after catheter ablation. Direct effects of adenosine on the AP, possibly via AP membrane potential hyperpolarization, are the dominant mechanism of adenosine-induced AP conduction after ablation. Dormant AP conduction is associated with higher rates of recurrent AP conduction requiring repeat ablation.
Body Mass Index and the Risk of All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus
Authors: Zhao Wenhui , Katzmarzyk Peter T. , Horswell Ronald , Wang Yujie , Li Weiqin , Johnson Jolene , Heymsfield Steven B. , Cefalu William T. , Ryan Donna H. , Hu Gang 
Published: November 2014

Background—
Several prospective studies have evaluated the association between body mass index (BMI) and death risk among patients with diabetes mellitus; however, the results have been inconsistent.

Methods and Results—

We performed a prospective cohort study of 19 478 black and 15 354 white patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with all-cause mortality. During a mean follow-up of 8.7 years, 4042 deaths were identified. The multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard ratios for all-cause mortality associated with BMI levels (18.5–22.9, 23–24.9, 25–29.9, 30–34.9 [reference group], 35–39.9, and ≥40 kg/m
2
) at baseline were 2.12 (95% confidence interval [CI], 1.80–2.49), 1.74 (95% CI, 1.46–2.07), 1.23 (95% CI, 1.08–1.41), 1.00, 1.19 (95% CI, 1.03–1.39), and 1.23 (95% CI, 1.05–1.43) for blacks and 1.70 (95% CI, 1.42–2.04), 1.51 (95% CI, 1.27–1.80), 1.07 (95% CI, 0.94–1.21), 1.00, 1.07 (95% CI, 0.93–1.23), and 1.20 (95% CI, 1.05–1.38) for whites, respectively. When stratified by age, smoking status, patient type, or the use of antidiabetic drugs, a U-shaped association was still present. When BMI was included in the Cox model as a time-dependent variable, the U-shaped association of BMI with all-cause mortality risk did not change.

Conclusions—

The present study indicated a U-shaped association of BMI with all-cause mortality risk among black and white patients with type 2 diabetes mellitus. A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 kg/m
2
and ≥35 kg/m
2
and among whites with BMI <25 kg/m
2
and ≥40 kg/m
2
compared with patients with BMI of 30 to 34.9 kg/m
2
.
Left Ventricular Mass and the Risk of Sudden Cardiac Death: A Population‐Based Study
Authors: Laukkanen Jari A. , Khan Hassan , Kurl Sudhir , Willeit Peter , Karppi Jouni , Ronkainen Kimmo , Di Angelantonio Emanuele 
Published: November 2014

Background

Left ventricular (
LV
) mass ascertained using echocardiography may enhance risk stratification for sudden cardiac death. The objective of this study was to assess the association between left ventricular mass and the risk of sudden cardiac death in a population‐based cohort and determine its incremental value beyond conventional risk predictors.

Methods and Results

Assessment of
LV
mass was based on echocardiography in a sample of 905 middle‐aged men representative of the general population (aged 42 to 61 years). During the follow‐up period of 20 years, there were a total of 63 sudden cardiac deaths. In a comparison of the top versus the bottom quartile of
LV
mass adjusted by body surface area (>120 versus <89 g/m
2
), the multivariable adjusted hazard ratio was 2.57 (95%
CI
1.24 to 5.31,
P
=0.010). Further adjustment for
LV
function only modestly attenuated the risk of sudden cardiac death among men with
LV
mass of >120 g/m
2
(hazard ratio 2.29, 95%
CI
1.10 to 4.74,
P
=0.026). Addition of
LV
mass adjusted by body surface area to a conventional risk factor model for sudden cardiac death improved the integrated discrimination index by 0.033 (95%
CI
0.009 to 0.057,
P
=0.007) and the category‐free net reclassification index by 0.501 (95%
CI
0.092 to 0.911,
P
=0.016).

Conclusions

Indexed
LV
mass by body surface area is an independent predictor of sudden cardiac death and may help improve the risk prediction of sudden cardiac death beyond conventional cardiovascular risk factors.
Efficacy of Synchronous Verbal Training During Repetitive Transcranial Magnetic Stimulation in Patients With Chronic Aphasia
Authors: Wang Chih-Pin , Hsieh Chin-Yi , Tsai Po-Yi , Wang Chia-To , Lin Fu-Gong , Chan Rai-Chi 
Published: November 2014

Background and Purpose—
Although multiple studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may facilitate recovery after stroke, the efficacy of synchronous speech therapy integrated with an rTMS protocol has yet to be determined. We investigated language responses to this strategy and determined the longevity of the resulting therapeutic outcomes.

Methods—

Forty-five patients with stroke who presented with nonfluent aphasia were randomly assigned to the TMS
syn
group and underwent synchronous picture-naming training together with contralesional 1 Hz-rTMS for 10 daily sessions. The TMS
sub
group underwent subsequent picture-naming activity after the primed 1 Hz-rTMS, and the TMS
sham
group received concurrent naming task along with the sham 1 Hz-rTMS. The Concise Chinese Aphasia test and the picture-naming test were performed before, immediately, and after 3 months of the intervention.

Results—

TMS
syn
showed significantly superior results in Concise Chinese Aphasia test score (
P
<0.001), expression and description subtests (
P
<0.001), and action (
P
=0.02) and object naming activity (
P
=0.008); the superior results lasted for 3 months (
P
=0.005), in comparison with the TMS
sub
and TMS
sham
groups.

Conclusions—
We established a real-time model that involved implementing verbal tasks together with the rTMS protocol. Our results confirmed that the strategy yielded favorable outcomes that were of considerable longevity. The results also indicated that the rTMS protocol and language training can be combined to achieve outcomes superior to those obtained when used separately.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02120508.