bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow diversion for the treatment of posterior inferior cerebellar artery aneurysms: a novel classification and strategies
Authors: Srinivasan Visish M , Ghali Michael George Zaki , Reznik Oleg E , Cherian Jacob , Mokin Maxim , Dumont Travis M , Gaughen John R , Grandhi Ramesh , Puri Ajit S , Chen Stephen R , Johnson Jeremiah N , Kan Peter 
Published: October 2017

BackgroundThe pipeline embolization device (PED) is frequently used in the treatment of anterior circulation aneurysms, especially around the carotid siphon, with generally excellent results. However, treatment of posterior inferior cerebellar artery (PICA) aneurysms with flow diversion (FD) has not been specifically described or discussed. While there are reports of treating PICA aneurysms using placement of FD stents in the vertebral artery, there are no reports of treating these lesions by placement of flow diverting stents in the PICA vessel itself. Due to the unique anatomy and morphology of these aneurysms, it requires special attention. We assessed our multi-institutional experience treating these lesions, including the first reported cases of the PED placed within the PICA.MethodsInstitutional databases of neuroendovascular procedures were reviewed for cases of intracranial aneurysms treated with the PED. Patient and aneurysm data as well as angiographic imaging were reviewed for all cases of PICA aneurysms treated with the PED. PICA aneurysms were defined as aneurysms that involved the PICA. Vertebral aneurysms without disease in the PICA were excluded from the study.Results10 PICA aneurysms were treated during the study period. These were classified based on their morphology and location into two main types and five total subtypes for consideration of treatment with flow diversion. All aneurysms were successfully treated, with 8/10 completely obliterated and 2 with a partial reduction in size. Three patients had the PED placed entirely in the PICA and no patient suffered from a medullary or cerebellar stroke. All PEDs were patent and all patients were independent at the last follow-up.ConclusionsThe PED may be used successfully to treat select aneurysms of the PICA. We present the first described cases of successful PED treatment of PICA aneurysms with direct placement of the PED in the PICA vessel itself. The proposed classification system aids in that selection.
Influence of Natural American Spirit advertising on current and former smokers’ perceptions and intentions
Authors: Gratale Stefanie K , Maloney Erin K , Sangalang Angeline , Cappella Joseph N 
Published: October 2017

ObjectiveThis study sought to demonstrate causal effects of exposure to Natural American Spirit (NAS) advertising content on misinformed beliefs of current and former smokers, and to empirically establish these beliefs as a mechanism driving intentions to use NAS.MethodsOur study employed a randomised experimental design with 1128 adult daily, intermittent and former smokers. We compared participants who were exposed to NAS advertisements or claims made in the advertisements with those in a no-message control group to test the effects of NAS advertising content on inaccurate beliefs about NAS and attitudes and intentions towards the product.ResultsOne-way analysis of variance revealed that exposure to NAS advertisements produced inaccurate beliefs about the composition of NAS cigarettes among current and former smokers (p<0.05). Planned contrasts indicated a compilation of arguments taken directly from NAS advertisements resulted in significantly greater beliefs that NAS cigarettes are healthier/safer than other cigarettes (for former smokers, t(472)=3.63, p<0.001; for current smokers, t(644)=2.86, p=0.004), demonstrating that suggestive claims used in the brand’s marketing have effects on beliefs not directly addressed in the advertisements. Regression and mediation analyses showed that health-related beliefs predict attitudes towards NAS for current and former smokers, and mediate intentions to use NAS.ConclusionsThe findings of this study provide causal support for the need for further regulatory action to address the potentially harmful ramifications of claims used in NAS advertising.
Sivers effect in single spin asymmetry based on the covariant parton model
Authors: Saffar H. Mahdizadeh , Mirjalili A. , Tehrani S. Atashbar , Yazdanpanah M. M. 
Published: October 2017

Sivers effect is describing the correlation between the transverse polarization of nucleon and the transverse momentum, [Formula: see text], of its unpolarized constituent partons. This effect is an outstanding subject and in this regard, a great deal in recent years has been considered from experimental and phenomenological points of view. It also plays an essential role to extend our understanding from nucleon structure. Semi-inclusive DIS (SIDIS) process provides us an opportunity to access to Sivers function which is dependent on transverse momentum of partons. In this paper, for the first time the covariant parton model is used to deliver us the [Formula: see text] and [Formula: see text] dependence part of Sivers function. Based on this model, this combinatory dependence is arising out from the HERAPDF parametrization group. In this paper the other required parametrized functions in Sivers function is also changed with respect to Ref. 1. The unknown parameters which exist in Sivers function can be extracted, doing a global fit over the recent available experimental data, including HERMES, COMPASS and JLAB collaborations for the single spin asymmetry (SSA) in [Formula: see text] and [Formula: see text] meson production as well as kaon production to constrain the evolved strange quark. This is done, considering advanced mathematical manipulations to overcome the difficulties which exist to compute the required multiple integrals and finally employing the CERN MINIUTE program to do a global fit. Our results for SSA are in good agreement with the available experimental data. For more confirmation a comparison between our results and the ones from Ref. 2 is also done.
Small-Molecule Inhibition of PD-1 Transcription Is an Effective Alternative to Antibody Blockade in Cancer Therapy
Authors: Taylor Alison , Rothstein David , Rudd Christopher E. 
Published: October 2017

Abstract
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase, GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small-molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti–PD-1 and PD-L1–blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings. Furthermore, the conditional genetic deletion of GSK-3α/β reduced PD-1 expression on CD8+ T cells and limited B16 pulmonary metastasis to the same degree as PD-1 gene deficiency. In each model, GSK-3i inhibited PD-1 expression on tumor-infiltrating lymphocytes, while increasing Tbx21 (T-bet) transcription, and the expression of CD107a+ (LAMP1) and granzyme B (GZMB) on CD8+ T cells. Finally, the adoptive transfer of T cells treated ex vivo with a GSK-3 inhibitor delayed the onset of EL4 lymphoma growth to a similar extent as anti–PD-1 pretreatment. Overall, our findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer therapy to a similar degree as PD-1–blocking antibodies.
Significance: These findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer therapy to a similar degree as PD-1 blocking antibodies, offering a next-generation approach in the design of immunotherapeutic approaches for cancer management. Cancer Res; 78(3); 706–17. ©2017 AACR.
A Synthetic CD8α:MyD88 Coreceptor Enhances CD8+ T-cell Responses to Weakly Immunogenic and Lowly Expressed Tumor Antigens
Authors: Kaczanowska Sabina , Joseph Ann Mary , Guo Jitao , Tsai Alexander K , Lasola Jackline Joy , Younger Kenisha , Zhang Yuji , Gonzales Cruz Velasco , Davila Eduardo 
Published: October 2017

AbstractT cell–based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T-cell efficacy, including suboptimal T-cell receptor (TCR) activation and an immunosuppressive tumor environment. Here, we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T-cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88–engineered T cells exhibited increased proliferation and expression of effector and costimulatory molecules in a tumor antigen–dependent manner. These effects were accompanied by elevated activation of TCR and Toll-like receptor signaling-related proteins. CD8α:MyD88–expressing T cells improved antitumor responses in mice. Enhanced antitumor activity was associated with a unique tumor cytokine/chemokine signature, improved T-cell infiltration, reduced markers of T-cell exhaustion, elevated levels of proteins associated with antigen presentation, and fewer macrophages with an immunosuppressive phenotype in tumors. Given these observations, CD8α:MyD88 represents a unique and versatile approach to help overcome immunosuppression and enhance T-cell responses to tumor antigens. Cancer Res; 77(24); 7049–58. ©2017 AACR.
[18F]fluorothymidine PET Informs the Synergistic Efficacy of Capecitabine and Trifluridine/Tipiracil in Colon Cancer
Authors: Kim Seog-Young , Jung Jin Hwa , Lee Haeng Jung , Soh Hyunsu , Lee Sang Ju , Oh Seung Jun , Chae Sun Young , Lee Jai Hyuen , Lee Seung Jin , Hong Yong Sang , Kim Tae Won , Moon Dae Hyuk 
Published: October 2017

Abstract
In cancer therapy, enhanced thymidine uptake by the salvage pathway can bypass dTMP depletion, thereby conferring resistance to thymidylate synthase inhibition. We investigated whether sequential combination therapy of capecitabine and trifluridine/tipiracil (TAS-102) could synergistically enhance antitumor efficacy in colon cancer xenograft models. We also examined 3'-deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET as a means to predict therapeutic response to a sequential combination of capecitabine and trifluridine/tipiracil. [3H]FLT uptake after 5-fluorouracil treatment in vitro and [18F]FLT uptake after capecitabine (360 mg/kg/day) in athymic nude mice (Balb/c-nu) with xenografts (n = 10–12 per group) were measured using eight human colon cancer cell lines. We determined the synergistic effects of sequential combinations of 5-fluorouracil and trifluridine in vitro as well as the sequential combination of oral capecitabine (30–360 mg/kg) and trifluridine/tipiracil (trifluridine 75 or 150 mg/kg with tipiracil) in six xenograft models (n = 6–10 per group). We observed significant increases in [3H]FLT uptake in all cell lines and [18F]FLT uptake in five xenograft models after 5-fluorouracil and capecitabine treatment, respectively. Increased [18F]FLT uptake after capecitabine followed by extinction of uptake correlated strongly with tumor growth inhibition (ρ = −0.81, P = 0.02). The effects of these combinations were synergistic in vitro. A synergy for sequential capecitabine and trifluridine/tipiracil was found only in mouse xenograft models showing increased [18F]FLT uptake after capecitabine. Our results suggest that the sequential combination of capecitabine and trifluridine/tipiracil is synergistic in tumors with an activated salvage pathway after capecitabine treatment in mice, and [18F]FLT PET imaging may predict the response to capecitabine and the synergistic antitumor efficacy of a sequential combination of capecitabine and trifluridine/tipiracil. Cancer Res; 77(24); 7120–30. ©2017 AACR.
SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance
Authors: Orlacchio Arturo , Ranieri Michela , Brave Martina , Arciuch Valeria Antico , Forde Toni , De Martino Daniela , Anderson Karen E. , Hawkins Phillip , Di Cristofano Antonio 
Published: October 2017

Abstract
Activation of the PI3K–AKT signaling cascade is a common critical event during malignant transformation. In this study, we used thyroid gland epithelial cells and a series of genetically engineered mouse strains as model systems to demonstrate that, although necessary, AKT activation is not sufficient for PI3K-driven transformation. Instead, transformation requires the activity of the PDK1-regulated AGC family of protein kinases. In particular, SGK1 was found to be essential for proliferation and survival of thyroid cancer cells harboring PI3K-activating mutations. Notably, cotargeting SGK1 and AKT resulted in significantly higher growth suppression than inhibiting either PI3K or AKT alone. Overall, these findings underscore the clinical relevance of AKT-independent pathways in tumors driven by genetic lesions targeting the PI3K cascade. Cancer Res; 77(24); 6914–26. ©2017 AACR.
Caveolae-Mediated Endocytosis as a Novel Mechanism of Resistance to Trastuzumab Emtansine (T-DM1)
Authors: Sung Matthew , Tan Xingzhi , Lu Bingwen , Golas Jonathan , Hosselet Christine , Wang Fang , Tylaska Laurie , King Lindsay , Zhou Dahui , Dushin Russell , Myers Jeremy S. , Rosfjord Edward , Lucas Judy , Gerber Hans-Peter , Loganzo Frank 
Published: October 2017

Abstract
Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate (ADC) that has demonstrated clinical benefit for patients with HER2+ metastatic breast cancer; however, its clinical activity is limited by inherent or acquired drug resistance. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2+ tumors, are not well understood. We used HER2+ cell lines to develop models of T-DM1 resistance using a cyclical dosing schema in which cells received T-DM1 in an “on-off” routine until a T-DM1–resistant population was generated. T-DM1–resistant N87 cells (N87-TM) were cross-resistant to a panel of trastuzumab-ADCs (T-ADCs) with non–cleavable-linked auristatins. N87-TM cells do not have a decrease in HER2 protein levels or an increase in drug transporter protein (e.g., MDR1) expression compared with parental N87 cells. Intriguingly, T-ADCs using auristatin payloads attached via an enzymatically cleavable linker overcome T-DM1 resistance in N87-TM cells. Importantly, N87-TM cells implanted into athymic mice formed T-DM1 refractory tumors that remain sensitive to T-ADCs with cleavable-linked auristatin payloads. Comparative proteomic profiling suggested enrichment in proteins that mediate caveolae formation and endocytosis in the N87-TM cells. Indeed, N87-TM cells internalize T-ADCs into intracellular caveolin-1 (CAV1)–positive puncta and alter their trafficking to the lysosome compared with N87 cells. T-DM1 colocalization into intracellular CAV1-positive puncta correlated with reduced response to T-DM1 in a panel of HER2+ cell lines. Together, these data suggest that caveolae-mediated endocytosis of T-DM1 may serve as a novel predictive biomarker for patient response to T-DM1. Mol Cancer Ther; 17(1); 243–53. ©2017 AACR.
CCL26 Participates in the PRL-3–Induced Promotion of Colorectal Cancer Invasion by Stimulating Tumor-Associated Macrophage Infiltration
Authors: Lan Qiusheng , Lai Wei , Zeng Yujie , Liu Lu , Li Shoufeng , Jin Shaowen , Zhang Yang , Luo Xingxi , Xu Heyang , Lin Xiangan , Chu Zhonghua 
Published: October 2017

AbstractBoth phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAM) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer invasion and metastasis by inducing TAM infiltration remains unclear. In the current study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We found that PRL-3 upregulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. In addition, IHC analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV colorectal cancer tissues and were associated with a worse prognosis in colorectal cancer patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL6 and IL8. In addition, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV colorectal cancer tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes colorectal cancer invasion and metastasis by upregulating CCL26 to induce TAM infiltration. Mol Cancer Ther; 17(1); 276–89. ©2017 AACR.
Effect of Magnesium on Glomerular Filtration Rate and Recovery of Hypertension in Women with Severe Preeclampsia
Authors: Kreepala Chatchai , Luangphiphat Wongsakorn  , Villarroel Alfredo  , Kitporntheranunt Maethaphan  , Wattanavaekin Krittanont , Piyajarawong Teeraya  
Published: October 2017

<b><i>Introduction:</i></b> Magnesium sulfate is used for preventing seizures in patients with severe preeclampsia. Previous studies have demonstrated that magnesium plays a significant role in the endothelial function and might have clinically beneficial vasodilating properties. <b><i>Objectives:</i></b> This study is aimed at evaluating the effect of magnesium sulfate on the glomerular filtration rate (GFR) during the first 24 h after delivery and during the duration of recovery from hypertension in preeclampsia. <b><i>Methods:</i></b> Severe preeclamptic patients who had normal serum creatinine levels (0.4–0.8 mg/dL) were included in the study. Twenty-three women with severe preeclampsia were divided into groups of 9, 8, and 6, and given 1.0, 1.5, and 2.0 g/h of magnesium sulfate, respectively. Magnesium sulfate infusion was used as seizure prophylaxis for 24 h after delivery. The cystatin C-based GFR was monitored for 24 h, and the blood pressure was recorded for 12 weeks postpartum. <b><i>Results:</i></b> Despite the minimal improvement of GFR 24-h after treatment initiation, survival analysis demonstrated a statistically significant relationship (log rank, <i>p</i> = 0.04) between magnesium dosage and recovery period from hypertension. The group receiving 2.0 g/h of magnesium experienced the shortest recovery period from hypertension (6.5 ± 1.8 days). Meanwhile, the other groups required 66.0 ± 26.9 and 48.3 ± 15.6 days to recover after 1.0 and 1.5 g/h of magnesium infusion, respectively. <b><i>Conclusion:</i></b> Magnesium sulfate has no impact on GFR improvement during the first 24 h after delivery. However, magnesium maintenance infusion at 2.0 g/h is capable of preventing seizure by optimizing the therapeutic magnesium level (4.8–8.4 mg/dL) and shortening the hypertensive episode in preeclampsia.
The Impact of De‐escalation of Antianginal Medications on Health Status After Percutaneous Coronary Intervention
Authors: Qintar Mohammed , Towheed Arooge , Tang Fengming , Salisbury Adam C. , Ho P. Michael , Grantham J. Aaron , Spertus John A. , Arnold Suzanne V. 
Published: October 2017

Background

Antianginal medications (
AAMs
) can be perceived to be less important after percutaneous coronary intervention (
PCI
) and may be de‐escalated after revascularization. We examined the frequency of
AAM
de‐escalation at discharge post‐
PCI
and its association with follow‐up health status.

Methods and Results

In a 10‐center
PCI
registry, the Seattle Angina Questionnaire was assessed before and 6 months post‐
PCI
.
AAM
de‐escalation was defined as fewer
AAMs
at discharge versus admission or >25% absolute dose decrease. Of 2743
PCI
patients (70% male),
AAM
were de‐escalated, escalated, and unchanged in 299 (11%), 714 (26%), and 1730 (63%) patients, respectively. Patients whose
AAM
were de‐escalated were more likely to report angina at 6 months, compared with unchanged or escalated
AAM
(34% versus 24% versus 21%;
P
<0.001). The association of
AAM
de‐escalation with health status was examined using multivariable models adjusting for the predicted risk of post‐
PCI
angina, completeness of revascularization, and the interaction of
AAM
de‐escalation×completeness of revascularization. There was a significant interaction between
AAM
de‐escalation and completeness of revascularization (
P
<0.001), suggesting that
AAM
de‐escalation was associated with greater impairment of health status among patients with incomplete revascularization. In patients with incomplete revascularization, de‐escalation of
AAM
at discharge was associated with 43% increased angina risk (relative risk, 1.43; 95% confidence interval, 1.26–1.63) and worse angina‐related health status at 6 months post‐
PCI
.

Conclusions

De‐escalation of
AAM
occurs in 1 in 10 patients post‐
PCI
, and it is associated with an increased risk of angina and worse health status, particularly among those with incomplete revascularization.
Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation
Authors: Scrutinio Domenico , Lanzillo Bernardo , Guida Pietro , Mastropasqua Filippo , Monitillo Vincenzo , Pusineri Monica , Formica Roberto , Russo Giovanna , Guarnaschelli Caterina , Ferretti Chiara , Calabrese Gianluigi 
Published: October 2017

Background and Purpose—
Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation.

Methods—
The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients.

Results—

Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858–0.910) for model 1 and 0.913 (95% confidence intervals, 0.884–0.942) for model 2. The Hosmer–Lemeshow χ
2
was 4.12 (
P
=0.249) and 1.20 (
P
=0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840–0.892) for model 1 and 0.850 (95% confidence intervals, 0.815–0.885) for model 2. The Hosmer–Lemeshow χ
2
was 8.86 (
P
=0.115) and 34.50 (
P
=0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25–0.71;
P
=0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14–0.68;
P
=0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at
https://goo.gl/fEAp81
.

Conclusions—
This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management.