bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective compromise of hypoplastic posterior communicating artery variants with aneurysms treatable by coil embolization: clinical and radiologic outcomes
Authors: Choi Hyun Ho , Cho Young Dae , Yoo Dong Hyun , Yeon Eung Koo , Lee Jeongjun , Lee Su Hwan , Kang Hyun-Seung , Cho Won-Sang , Kim Jeong Eun , Han Moon Hee 
Published: October 2018

BackgroundPosterior communicating artery (PcoA) compromise may serve as adjunctive treatment in patients with hypoplastic variants of PcoA who undergo coil embolization of PcoA aneurysms. However, procedural safety and the propensity for later recanalization are still unclear.ObjectiveTo evaluate clinical and radiologic outcomes of coil embolization in this setting, focusing on compromise of PcoA.MethodsAs a retrospective review, we examined 250 patients harboring 291 aneurysms of hypoplastic PcoAs, all consecutively treated by coil embolization between January 2004 and June 2016. PcoA compromise was undertaken in conjunction with 81 of the treated aneurysms (27.8%; incomplete 53; complete 28). Medical records and radiologic data were assessed during extended monitoring.ResultsDuring the mean follow-up of 33.9±24.6 months (median 36 months), a total of 107 (36.8%) coiled aneurysms showed recanalization (minor 50; major 57). Recanalization rates were as follows: PcoA preservation 40.5% (85/210); incomplete PcoA occlusion 34.0% (18/53); complete PcoA occlusion 14.3% (4/28). Aneurysms >7 mm (HR 3.40; P<0.01), retreatment for recanalization (HR 3.23; P<0.01), and compromise of PcoA (P<0.01) emerged from multivariate analysis as significant risk factors for recanalization. Compared with PcoA preservation, complete PcoA compromise conferred more favorable outcomes (HR 0.160), whereas incomplete compromise of PcoA fell short of statistical significance. Thromboembolic infarction related to PcoA compromise did not occur in any patient.ConclusionPcoA compromise in conjunction with coil embolization of PcoA aneurysms appears safe in hypoplastic variants of PcoA, helping to prevent recanalization if complete occlusion is achieved.
The safety and effectiveness of the LVIS stent system for the treatment of wide-necked cerebral aneurysms: final results of the pivotal US LVIS trial
Authors: Fiorella David , Boulos Alan , Turk Aquilla S , Siddiqui Adnan H , Arthur Adam S , Diaz Orlando , Lopes Demetrius K 
Published: October 2018

IntroductionThe LVIS stent system (LVIS and LVIS Junior) is a self-expanding, retrievable, microstent system indicated for the treatment of wide-necked cerebral aneurysms (WNAs). The present pivotal study was performed to evaluate the safety and effectiveness of this device.MethodsThe US LVIS pivotal trial was a prospective, multicenter, single-arm, interventional study conducted at 21 US centers. The study enrolled 153 adults with WNAs of the anterior and posterior circulations. The study was conducted under good clinical practices and included independent adjudication of all adverse events. The primary effectiveness endpoint was defined as successful aneurysm treatment with the LVIS System as evidenced by complete (100%) aneurysm occlusion at 12 months on conventional angiography without retreatment and without significant (≥50%) stenosis of the treated artery at 12 months as determined by an independent core laboratory. The primary safety endpoint was defined as the rate of stroke or death within 30 days, or ipsilateral stroke or neurologic death with 12 months.ResultsOne hundred and fifty-three patients enrolled at 21 investigational sites underwent attempted LVIS-assisted coil embolization. The mean age was 58.3±10.5 years and the majority of the participants (110/153, 71.9%) were female. Fifty-seven aneurysms (57/153, 37.3%) arose from the anterior cerebral artery, 43 (43/153, 28.1%) from the internal carotid artery, 17 (17/153, 11.1%) from the middle cerebral artery, 27 (27/153, 17.6%) from the basilar artery, six (6/153,3.9 %) from the PCA, and two from the vertebral artery. A single aneurysm arose from the superior cerebellar artery. The mean aneurysm dome height was 6.0±2.2 mm and mean width 5.5±2.3 mm. Mean neck width was 4.2±1.4 mm. A total of 22 participants presented for re-treatment of a previously ruptured (>30 days prior to treatment) target aneurysm. The primary effectiveness endpoint was observed in 70.6% (108/153) in the intent to treat population (ITT). Of the evaluable participants with follow-up 12-month angiography, 79.1 % (110/139) demonstrated complete occlusion– 92.1% (128/139) in this population demonstrated ≥95% occlusion and 95% demonstrated ≥90% occlusion (132/139). Eight participants (5.2%, 8/153) had at least one primary safety event in the ITT population.ConclusionThe LVIS stent system allows safe and highly effective coil embolization of WNAs.Clinical registration numberNCT01793792.
DNA Polymerase Eta Prevents Tumor Cell-Cycle Arrest and Cell Death during Recovery from Replication Stress
Authors: Barnes Ryan P. , Tsao Wei-Chung , Moldovan George-Lucian , Eckert Kristin A. 
Published: October 2018

Abstract

Neoplastic transformation and genome instability are enhanced by replication stress, conditions that slow or stall DNA replication forks. Consequently, cancer cells require multiple enzymes and checkpoint signaling pathways to mitigate replication stress for their viability and proliferation. Targeting proteins that enhance cancer cell survival during replication stress is a recent approach in clinical strategies, especially when targets produce synthetic lethality. DNA polymerase eta (Pol η) has many key functions in genome stability, particularly for translesion synthesis. Here we demonstrate that endogenous Pol η displays significant protein induction and forms intense foci throughout the nucleus in response to replication stress induced by drugs that do not directly form DNA adducts. During replication stress, Pol η-deficient cells displayed hyperactivation of the ATR replication checkpoint and arrested late in the cell cycle. During recovery from replication stress, Pol η-deficient cells continue to display aberrant phenotypes, including delayed cell-cycle progression, apoptosis, and cell survival. Depletion or inhibition of ATR was synthetically lethal with Pol η deficiency, particularly when tumor cells were treated with replication stress-inducing drugs. Together our data expand knowledge of the cellular environments that increase endogenous Pol η expression beyond DNA damaging agents and demonstrate that Pol η regulation is central to the replication stress response. Because Pol η is aberrantly expressed in several tumor types, our results are critical for developing more effective chemotherapy approaches and identify coinhibition of Pol η and ATR as a potential therapeutic strategy.

Significance:
This study demonstrates that replication stress upregulates Pol η (POLH) in tumor cells and reveals a role for Pol η in tumor cell recovery following replication stress.
CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma
Authors: Ravindran Menon Dinoop , Luo Yuchun , Arcaroli John J. , Liu Sucai , KrishnanKutty Lekha Nair , Osborne Douglas G. , Li Yang , Samson Jenny Mae , Bagby Stacey , Tan Aik-Choon , Robinson William A. , Messersmith Wells A. , Fujita Mayumi 
Published: October 2018

Abstract

Cancers are composed of heterogeneous subpopulations with various tumor-initiating capacities, yet key stem cell genes associated with enhanced tumor-initiating capacities and their regulatory mechanisms remain elusive. Here, we analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer tissues and identified enrichment of tumor-initiating cells in MHC class I-hi cells, where CDK1, a master regulator of the cell cycle, was upregulated. Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacologic agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle. Proteomic analysis revealed an interaction between CDK1 and the pluripotent stem cell transcription factor Sox2. Blockade or knockdown of CDK1 resulted in reduced phosphorylation, nuclear localization, and transcriptional activity of Sox2. Knockout of Sox2 in CDK1-overexpressing cells reduced CDK1-driven tumor-initiating capacity substantially. Furthermore, GSEA analysis of CDK1hi tumor cells identified a pathway signature common in all three cancer types, including E2F, G2M, MYC, and spermatogenesis, confirming a stem-like nature of CDK1hi tumor cells. These findings reveal a previously unrecognized role for CDK1 in regulating tumor-initiating capacity in melanoma and suggest a novel treatment strategy in cancer via interruption of CDK1 function and its protein-protein interactions.

Significance:
These findings uncover CDK1 as a new regulator of Sox2 during tumor initiation and implicate the CDK1–Sox2 interaction as a potential therapeutic target in cancer.
Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies
Authors: Matthews Natalie H. , Fitch Katherine , Li Wen-Qing , Morris J. Steven , Christiani David C. , Qureshi Abrar A. , Cho Eunyoung 
Published: October 2018

AbstractExposure to environmental trace elements has been studied in relation to many cancers. However, an association between exposure to trace elements and skin cancer remains less understood. Therefore, we conducted a systematic review of published epidemiologic literature examining the association between exposure to trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We identified epidemiologic studies investigating exposure to arsenic, cadmium, chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans. Among the minerals, arsenic, selenium, and zinc had more than five studies available. Exposure to arsenic was associated with increased risk of keratinocyte carcinoma, while too few studies existed on melanoma to draw conclusions. Exposure to selenium was associated with possible increased risk of keratinocyte carcinoma. Studies of zinc and skin cancer were case–control in design and were found to have inconsistent associations. The data on the association between cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to draw any conclusions. In summary, epidemiologic studies on exposure to trace elements and cutaneous malignancies are limited. Studies with larger sample sizes and prospective designs are warranted to improve our knowledge of trace elements and skin cancer.
Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer
Authors: Kitajima Shunsuke , Ivanova Elena , Guo Sujuan , Yoshida Ryohei , Campisi Marco , Sundararaman Shriram K. , Tange Shoichiro , Mitsuishi Yoichiro , Thai Tran C. , Masuda Sayuri , Piel Brandon P. , Sholl Lynette M. , Kirschmeier Paul T. , Paweletz Cloud P. , Watanabe Hideo , Yajima Mamiko , Barbie David A. 
Published: October 2018

Abstract

KRAS-driven lung cancers frequently inactivate TP53 and/or STK11/LKB1, defining tumor subclasses with emerging clinical relevance. Specifically, KRAS-LKB1 (KL)–mutant lung cancers are particularly aggressive, lack PD-L1, and respond poorly to immune checkpoint blockade (ICB). The mechanistic basis for this impaired immunogenicity, despite the overall high mutational load of KRAS-mutant lung cancers, remains obscure. Here, we report that LKB1 loss results in marked silencing of stimulator of interferon genes (STING) expression and insensitivity to cytoplasmic double-strand DNA (dsDNA) sensing. This effect is mediated at least in part by hyperactivation of DNMT1 and EZH2 activity related to elevated S-adenylmethionine levels and reinforced by DNMT1 upregulation. Ectopic expression of STING in KL cells engages IRF3 and STAT1 signaling downstream of TBK1 and impairs cellular fitness, due to the pathologic accumulation of cytoplasmic mitochondrial dsDNA associated with mitochondrial dysfunction. Thus, silencing of STING avoids these negative consequences of LKB1 inactivation, while facilitating immune escape.

Significance:
Oncogenic KRAS-mutant lung cancers remain treatment-refractory and are resistant to ICB in the setting of LKB1 loss. These results begin to uncover the key underlying mechanism and identify strategies to restore STING expression, with important therapeutic implications because mitochondrial dysfunction is an obligate component of this tumor subtype.
See related commentary by Corte and Byers, p. 16.
This article is highlighted in the In This Issue feature, p. 1
Resenha: A América Latina. Males de Origem
Authors: Castro Rita de Cássia Marques Lima de 
Published: October 2018

Trata-se de uma resenha da obra de Manoel Bomfim, escrita em 1903, em Paris: A América Latina. Males de Origem. Esta obra balança as estruturas de pensamento vigentes no início do século XX, trazendo considerações sobre os males de origem que assomam os países americanos de colonização ibérica. As ideias do médico e educador Manoel Bomfim, ousadas e contra a corrente dominante na época, merecem ser rememoradas e colocadas em pauta de discussão, em pleno século XXI, visto que se mantêm atuais e provocadoras. Afinal, os dentes de ixode de séculos de parasitismo europeu apresentam-se, ainda, insistentemente, na história e na evolução da rica em desafios de investigação, complexa e instigante América Latina.
Prometeo, El Grill y la Migración
Authors: Paz-y-Miño Cepeda Isabel 
Published: October 2018

La crisis económica de Ecuador de 1999, ocasionó la migración al exterior de tres millones de ciudadanos. Ese éxodo masivo ha sido el mayor en la historia de este país latinoamericano. El presente artículo indaga en las consecuencias de la migración vistas desde el arte cinematográfico. Analiza dos películas de directores ecuatorianos: la ficción Prometeo deportado de Fernando Mieles, realizada en 2010 y que cuenta la historia de un grupo de ecuatorianos encerrados en una sala de un aeropuerto europeo, en espera de ser deportados, y el documental El grill de César de Darío Aguirre, producido en 2013, que narra el retorno al país del hijo migrante y el reencuentro con su padre. Más allá de los estudios y de las cifras que se pueden citar en torno al problema social más significativo para el Ecuador en la década inicial del Siglo XXI, es a través del arte, y en este caso específico del cine, como se puede “sentir” lo que ha representado para este país el drama de la migración.
Abstract TMP48: Subcortical Volumes Associated With Post-Stroke Motor Performance Vary Across Impairment Severity, Time Since Stroke, and Lesion Laterality: an ENIGMA Stroke Recovery Analysis
Authors: Liew Sook-Lei , Jahanshad Neda , MacIntosh Bradley J , Robertson Andrew D , Wang Junping , Soekadar Surjo , Marguiles Daniel S , Lotze Martin , Domin Martin , Byblow Winston D , Stinear Cathy M , Westlye Lars T , Ramos Ander , Birbaumer Niels , Wiest Roland , Ward Nick , Anglin Julia M , Winstein Carolee J , Aziz-Zadeh Lisa , Roberts Pamela , Goud Anil , Borich Michael R , Wittenberg George , Lang Catherine E , Kuceyeski Amy , Kautz Steven , Hanlon Colleen , Cramer Steven C , Thompson Paul M ,   on behalf of the ENIGMA Stroke Recovery working group
Published: October 2018

Associations between subcortical gray matter volume and motor performance post-stroke are unclear, partly because many stroke MRI studies are underpowered. Potential influences of the severity of motor impairment, lesion laterality, and time since stroke on these associations is also unknown.
Here, we addressed these questions using a large dataset (n=629) from the ENIGMA Stroke Recovery working group (http://enigma.usc.edu). Regression analyses examined brain volumes as predictors of motor scores. ENIGMA FreeSurfer protocols extracted volumes from 16 subcortical regions on T1-weighted MRIs; segmentations were manually quality controlled. Motor scores were calculated as a percentage of the maximum possible score (100% = no impairment). Covariates (e.g., age, sex, intracranial volume) were modeled. Statistical significance was assessed nonparametrically by permutation. Separate analyses were performed, stratifying by motor severity and time since stroke. Each analysis was also subdivided by lesioned hemisphere.

The
motor severity analysis
(Table 1A) used subgroups of mild (66.7-99.9%), moderate (33.3-66.6%), and severe (0-33.2%). Significant associations were found for mild and moderate, but not severe, stroke; only the left hemisphere stroke group showed further significant results.

The
time since stroke analysis
(Table 1B) used subgroups of acute (<1 month), subacute (1-6 months), and chronic (>6 months). Significant associations were found in chronic stroke, but not acute, subacute. Left versus right hemisphere lesions generated different results in chronic stroke.

Overall, these results show that the most significant associations between subcortical volumes and motor outcomes are in chronic mild-to-moderate stroke. Stroke subgroups may recover via disparate mechanisms; establishing biomarkers of impairment and disability across stroke subgroups may be useful for clinical trials.
Abstract TP373: Regional Phoenix Stroke Work Group Improves Stroke Patient Care
Authors: Denke Nancy J , Duke Kimberly , Liable Deborah A , Loomis Ron , Martinez Hope ,   Phoenix Stroke Workgroup
Published: October 2018

Background and Purpose:
The Phoenix Stroke Workgroup (PSW) is comprised of volunteer staff of doctors, nurses and EMS to focus on the partnership between EMS and PSCs. Data is collected and shared within this workgroup to examine the delivery of emergent stroke care at each specific facility.

PSW evaluated yearly data by voluntary submission of predetermined critical metrics. PSW established benchmarks and set limits for each measure (i.e. Door to Needle (DTN) benchmark was 45 min with a limit of 75 min). Facilities exceeding the set limits were required to implement an action plan, review by EMS, and submit the next two quarters data for review by PSW.
We aim to determine if this collaboration has improved patient care, specifically: door to needle (DTN) times, complication rates, rates of tissue plasminogen activator and endovascular stroke treatments.

Methods:
Stroke coordinators volunteered all facility data from Get With The Guidelines AHA data base yearly with coordination from the local AHA chapter. We then compared clinical metrics from the 19 PSC’s for the years 2014, 2015, and 2016 for door to needle (DTN) times, complication rates, rates of tissue plasminogen activator and endovascular stroke treatments.

Results:
This collaboration decreased EMS DTN and POV (private vehicle) DTN times by 8 minutes and 9 minutes respectively during the 3-year study period. The utilization rate of TPA and endovascular treatment increased from 13.8 to 14.7% and 3 to 4.4%, but complications increased 2% from 3 to 5%.

Conclusion:
PSW collaboration improved the DTN times and utilization of both TPA and Endovascular treatment in the Phoenix metropolitan area. Future directions include collaboration to evaluate endovascular treatment times, bypass or transfer policies and statewide collaboration to continue to improve stroke patient care.
Abstract WP53: Improved Prediction of the Final Infarct From Acute Stroke Neuroimaging Using Deep Learning
Authors: Niu Yilin , Gong Enhao , Xu Junshen , Pauly John , Zaharchuk Greg 
Published: October 2018

Introduction:
Predicting the final infarct for acute stroke from acute imaging is valuable for triage and prognosis (1). We developed and tested a Deep Learning model, based on a 3D Convolutional Neural Network (CNN) architecture, to predict the lesion based on a 30-90 day scan from acute images.

Method:
The model has 3 advantages compared with traditional CNN (Figure):

1. 3D CNN more efficiently utilizes spatial information across multiple slices.
2. Patches instead of entire images are used as inputs. With a patch-based approach, we avoid the impact of minimally-relevant information from distant voxels. Training on patches also prevents over-fitting by augmenting each image into thousands of samples.
3. Multi-scale structure is used by processing patches with different resolutions. Segmentation based on a single scale image cannot fully capture varying local information and may miss contextual information. We use two scales of patches to learn both local and global context.
The model was trained and tested using the MICCAI ISLES 2017 challenge dataset (2), which consists of 43 cases with acute ADC and PWI maps paired with annotated final infarct segmentations at day 30-90. Dice score coefficient (DSC) and AUC for segmentation were used as quality metrics.

Results:
Using 70% of dataset for training and rest for testing, we achieved a DSC of 0.43±0.18 and 0.90 for AUC. As a comparison, the winning entry for the ISLES 2016 challenge achieved a DSC of 0.31, while several previous research works (threshold based, cluster based, Generalized Linear Model, etc.) achieve up to 0.84 AUC (1).

Conclusion:
We demonstrate that a deep learning approach can predict the final stroke lesion based on acute diffusion and perfusion neuroimaging data. Given its inherent speed, high performance, and capacity for further training, deep learning is a promising method for stroke lesion outcome prediction.

References
1. Rekik et al., Neuroimage Clin 2012;

2.
http://www.isles-challenge.org/
Abstract WP84: National Inpatient Sample Analysis of Unruptured Intracranial Aneurysms: Trends in Treatment and In-Hospital Complications 2002-2014
Authors: Salahuddin Hisham , Siddiqui Nauman , Zaidi Syed F , Jumaa Mouhammad 
Published: October 2018

Introduction:
Our objective was to determine trends in treatment preference and in-hospital complications of patients undergoing elective and non-elective treatment for unruptured intracranial aneurysms (UIA) in the United States over a 12-year period.

Methods:
We identified patients from the National Inpatient Sample database who were electively or non-electively admitted to the hospital with a primary ICD 9 diagnosis of unruptured intracranial aneurysm (437.3) from 2002 to 2014. We identified the method of treatment (surgical clipping or endovascular coiling) and studied in-hospital complications.

Results:
We identified 111,811 patients with UIAs between 2002 to 2014. Of these patients, 89,599 (80.1%) of patients were electively admitted. Approximately 47% (42,112) of patients underwent surgical clipping, while 53% (47,487) of patients underwent endovascular coiling. Of 22,212 patients who were admitted non-electively, 38.6% (8570) patients underwent surgical clipping and 61.4% (13,642) underwent endovascular coiling. There was a significantly higher proportion of patients treated with endovascular coiling for non-electively admitted patients as compared to elective admissions.

For electively treated UIAs there were no significant differences in in-hospital mortality between the two treatment groups. Iatrogenic cerebrovascular accidents and intracranial hemorrhage were significantly less common in the endovascular coiling group throughout the study period.
For non-electively treated UIAs, there was no significant difference in hospital mortality over the 12-year period. The rate of iatrogenic cerebrovascular accidents was generally lower for endovascular coiling with the exception of 2003. Endovascular coiling resulted in a significantly lower rate of iatrogenic cerebrovascular accidents in 2004 and 2008-2012. Intracranial hemorrhage was significantly less common in the endovascular group in 2004 and 2008-2014.

Conclusions:
Endovascular therapy has lower rates of in-hospital iatrogenic cerebrovascular accidents, and similar rates of mortality. The rate of endovascular and surgical therapies has plateaued since approximately 2005.