bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy
Authors: Rai Ansaar T , Domico Jennifer R , Buseman Chelsea , Tarabishy Abdul R , Fulks Daniel , Lucke-Wold Noelle , Boo SoHyun , Carpenter Jeffrey S 
Published: September 2017

BackgroundM2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking.MethodologyPatients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the ‘stroke belt’ were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data.ResultsThere were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5–18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p<0.0001). An NIHSS score ≥9 was the optimal cut-off point for predicting poor outcomes (sensitivity 85.7%, specificity 67.4%). 71 (61%) patients had an NIHSS score ≥9 and 45 (39%) an NIHSS score <9. The rate of good-outcome was 22.6% for NIHSS score ≥9 versus 78.4% for NIHSSscore <9 (OR=0.08, 95% CI 0.03 to 0.21, p<0.0001). Mortality was 42% for NIHSS score ≥9 versus 2.7% for NIHSS score <9 (OR=26, 95% CI 3.3 to 202, p<0.0001). Infarct volume was 57 (±55.7) cm3for NIHSS score ≥9 versus 30 (±34)cm3for NIHSS score <9 (p=0.003). IV recombinant tissue plasminogen activator (rtPA) administered in 28 (24%) patients did not affect outcomes. The rate of M2 occlusions was 7 (95% CI 5 to 9)/100 000 people/year (3%, 95% CI 2% to 4%), giving an incidence of 21 176 (95% CI 15 282 to 29 247)/year. Combined with M1, internal carotid artery terminus and basilar artery, this yields a ‘large vessel occlusion (LVO)+M2’ rate of 31 (95% CI 26 to 35)/100 000 people/year and a national incidence of 99 227 (95% CI 84 004 to 112 005) LVO+M2 strokes/year.ConclusionM2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.
Comparing different thrombectomy techniques in five large-volume centers: a ‘real world’ observational study
Authors: Hesse Amélie Carolina , Behme Daniel , Kemmling André , Zapf Antonia , Hokamp Nils Große , Frischmuth Isabelle , Maier Ilko , Liman Jan , Tsogkas Ioannis , Buhk Jan-Hendrik , Tran Julia , Fiehler Jens , Mpotsaris Anastasios , Schramm Peter , Berlis Ansgar , Knauth Michael , Psychogios Marios-Nikos 
Published: September 2017

Background and purposeThrombectomy has become the standard of care for acute ischaemic stroke due to large vessel occlusion. Aim of this study was to compare the radiological outcomes and time metrics of the various thrombectomy techniques.MethodsIn this retrospective, multicenter study we analysed the data of 450 patients with occlusion of the anterior circulation, treated in five high-volume center from 2013 to 2016. The treatment techniques were divided in three categories: first-pass use of a large-bore aspiration-catheter; first-pass use of a stent-retriever; and primary combined approach (PCA) of an aspiration-catheter and stent-retriever. Primary endpoints were successful reperfusion and groin to reperfusion time. Secondary endpoints were the number of attempts and occurrence of emboli in new territory (ENT). The primary analysis was based on the intention to treat groups (ITT).ResultsThe ITT-analysis showed significantly higher reperfusion rates, with 86% of successful reperfusion in the PCA-group compared with 73% in the aspiration group and 65% in the stent-retriever group. There was no significant difference in groin to reperfusion time regarding the used technique. The secondary analysis showed an impact of the technique on the number of attempts and the occurrence of ENTs. Lowest ENT rates and attempts were reported with the combined approach.ConclusionsThe combined first-pass deployment of a stent-retriever and an aspiration-catheter was the most effective technique for reperfusion of anterior circulation large vessel occlusion. Our results correlate with the latest single-centrere studies, reporting very high reperfusion rates with PCA variations.
Long term follow-up of bifurcation aneurysms treated with braided stent assisted coiling and complex T- and Y- stent constructs
Authors: Cheung Nicholas K , Chiu Albert HY , Cheung Andrew , Wenderoth Jason D 
Published: September 2017

BackgroundStent assisted coil embolization (SACE) of bifurcation aneurysms is challenging. Heterogeneous results have been achieved to date, but largely for laser cut stents. While braided stents offer multiple technical advantages, their long term efficacy has yet to be validated.ObjectiveTo report the first long term 18 month results for the durability of bifurcation aneurysms treated with braided stents.Materials and methodsOver a 4 year period, 59 consecutive patients with 60 bifurcation aneurysms underwent elective braided SACE across three Australian neurovascular centers. 17 of these aneurysms underwent T- or Y-shaped stent constructs. All patients had immediate, 6 month and 18 month clinical and radiological follow-up. Radiological assessment was made on modified Raymond–Roy occlusion scores while clinical assessment was based on the modified Rankin Scale. Subgroup analysis of 17 aneurysms treated with multi-stent constructs was conducted.Results6 month follow-up data were available for 59 aneurysms and 18 month follow-up data for 58 aneurysms. Satisfactory aneurysm occlusion was achieved in 97% at inception and at 6 months, and 98% at 18 months. Good neurological outcomes were achieved in 95% at 18 months. Similar satisfactory results were achieved with the multi-stent construct cohort. Intraprocedural thromboembolic events were recorded in 5% and delayed events in 2%. Technical complications were found in 5%. All complication rate was 13%.ConclusionBraided SACE was safe, efficacious, and durable at the long term 18 month follow-up, including for multi-stent constructs. Preliminary results indicate favorable clinical and radiological outcomes compared with laser cut stents.
Significant reduction in hospital-acquired thrombosis: impact of national risk assessment and real-time feedback
Authors: Rowswell Huw Raymond , Nokes Timothy J C 
Published: September 2017

ObjectiveSince 2010, National Health Service hospitals in England have been incentivised to risk assess for Venous Thromboembolism (VTE) in all adult patients admitted, using a national tool. We studied the impact of this, together with local real-time reporting of VTE events to senior clinicians, on cases of hospital-acquired thrombosis (HAT) diagnosed, since 2010.MethodsThis was an observational cohort study reviewing all cases of VTE diagnosed between January 2010 and December 2016 in a single teaching hospital. These were matched against the number of patients admitted to produce crude incidence rates per thousand admissions. Similarly, all cases associated with inadequate thromboprophylaxis (TP) measures were documented over the same period.ResultsBy the end of 2010, with 70% compliance with VTE risk assessment, improving to 90% (the national target) early in 2011, there were 217 HAT events from 103 845 admissions. In 2016, there were 176 HAT events from 119 128 admissions, being a significant reduction, relative risk (RR) 0.718 (95% CI 0.589 to 0.875; p=0.001). In 2010, there were 50 of 217 HAT events associated with inadequate TP, falling to 7 of 176 in 2016, also a significant reduction, RR 0.140 (95% CI 0.065 to 0.300; p=0.0001).ConclusionsNational guidance on VTE prevention and mandatory risk assessment linked to local real-time reporting of VTE events are associated with significant reductions both in total HAT events and those associated with inadequate TP.
Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology
Authors: Caprioli Marta , Carrara Greta , Sakellariou Garifallia , Silvagni Ettore , Scirè Carlo Alberto 
Published: September 2017

ObjectivesThe purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with tamoxifen.MethodsData were collected from the administrative healthcare database of Lombardy Region, Italy, from 2004 to 2013. This study follows a nested cohort design, including women with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole, exemestane or letrozole. The risk of RA related to the prescription of the different drugs was estimated by survival models for competing risks and the results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CI), adjusted for age and cancer severity.ResultsOut of total 10 493 women with breast cancer with a median (IQR) age of 66 (57–74), 7533 (71.8%) started an active treatment with AIs or tamoxifen. In this subgroup a total of 113 new cases of RA developed during the 26 105.9 person-year of 10 186 exposure periods, including time varying exposures in the same patient. Using tamoxifen as reference category, AIs therapy was associated with an increased risk of RA (adjusted HR 1.62 (95%1.03–2.56)), in particular in patients receiving anastrozole, even after adjusting for age and level of neoplasia: (adjusted HR 1.75 (95%1.07–2.86)).ConclusionsIn a large population-based sample of women with breast cancer, exposure to AIs compared with tamoxifen is associated with a significantly increased risk of RA, which is not influenced by the cancer severity and the relationship of age with indication to specific drugs.
Identifying chronic heavy alcohol use in emergency general surgery patients: a pilot study
Authors: Matar Maher M , Jewett Brent , Fakhry Samir M , Wilson Dulaney A , Ferguson Pamela L , Anton Raymond F , Sakran Joseph V 
Published: September 2017

BackgroundChronic heavy alcohol (CHA) use has been associated with perioperative complications. Emergency general surgery (EGS) patients are not routinely screened for CHA. If screened, it is usually for hazardous use of alcohol, using a survey such as the Alcohol Use Disorders Identification Test (AUDIT). This study screened EGS patients for CHA use using serum carbohydrate-deficient transferrin (%dCDT) level, a biomarker that has been validated as an indicator for CHA use, as well as the AUDIT. The purpose of this study was to determine the percent of EGS patients with CHA (as indicated by elevated %dCDT), and the relationship between %dCDT and AUDIT. Secondary aims included comparing the characteristics of EGS patients with and without CHA use, and evaluating the association of CHA use with negative clinical outcomes.MethodsEGS patients aged 21 and older admitted to the general surgery inpatient service of a tertiary hospital from July 2014 to June 2016 were invited to participate in this study. %dCDT levels above 1.7% were considered positive for CHA use, as were AUDIT scores ≥8.Results195 EGS patients were screened for inclusion and 91 (46.7%) agreed to participate. 14 (15.4%) were positive for hazardous alcohol use on AUDIT and 5 (5.5%) were positive for CHA by %dCDT. Positive predictive value of AUDIT for CHA was 21.4%. There was no correlation between positive scores on AUDIT and %dCDT.DiscussionIdentifying at risk patients early on in their hospital course may allow clinicians to institute treatments to mitigate and/or circumvent complications in such patients. This pilot study determined that 17.6% of participating EGS patients were positive for some type of alcohol misuse, but only 5.5% had CHA. Further research is needed to determine whether routine use of %dCDT would be beneficial in reducing perioperative complications in this patient population.Level of evidenceIII (diagnostic test).
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors
Authors: Malone Clare F. , Emerson Chloe , Ingraham Rachel , Barbosa William , Guerra Stephanie , Yoon Haejin , Liu Lin L. , Michor Franziska , Haigis Marcia , Macleod Kay F. , Maertens Ophélia , Cichowski Karen 
Published: September 2017

Abstract
Although agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here, we identify a promising combination therapy that kills NF1-mutant tumors by triggering catastrophic oxidative stress. Specifically, we show that mTOR and HDAC inhibitors kill aggressive nervous system malignancies and shrink tumors in vivo by converging on the TXNIP/thioredoxin antioxidant pathway, through cooperative effects on chromatin and transcription. Accordingly, TXNIP triggers cell death by inhibiting thioredoxin and activating apoptosis signal-regulating kinase 1 (ASK1). Moreover, this drug combination also kills NF1-mutant and KRAS-mutant non–small cell lung cancers. Together, these studies identify a promising therapeutic combination for several currently untreatable malignancies and reveal a protective nodal point of convergence between these important epigenetic and oncogenic enzymes.
Significance: There are no effective therapies for NF1- or RAS-mutant cancers. We show that combined mTOR/HDAC inhibitors kill these RAS-driven tumors by causing catastrophic oxidative stress. This study identifies a promising therapeutic combination and demonstrates that selective enhancement of oxidative stress may be more broadly exploited for developing cancer therapies. Cancer Discov; 7(12); 1450–63. ©2017 AACR.
This article is highlighted in the In This Issue feature, p. 1355
Somatic Superenhancer Duplications and Hotspot Mutations Lead to Oncogenic Activation of the KLF5 Transcription Factor
Authors: Zhang Xiaoyang , Choi Peter S. , Francis Joshua M. , Gao Galen F. , Campbell Joshua D. , Ramachandran Aruna , Mitsuishi Yoichiro , Ha Gavin , Shih Juliann , Vazquez Francisca , Tsherniak Aviad , Taylor Alison M. , Zhou Jin , Wu Zhong , Berger Ashton C. , Giannakis Marios , Hahn William C. , Cherniack Andrew D. , Meyerson Matthew 
Published: September 2017

Abstract
The Krüppel-like family of transcription factors plays critical roles in human development and is associated with cancer pathogenesis. Krüppel-like factor 5 gene (KLF5) has been shown to promote cancer cell proliferation and tumorigenesis and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here, we show that these alterations activate KLF5 by three distinct mechanisms: (i) Focal amplification of superenhancers activates KLF5 expression in squamous cell carcinomas; (ii) Missense mutations disrupt KLF5–FBXW7 interactions to increase KLF5 protein stability in colorectal cancer; (iii) Cancer type–specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with KLF5 overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.
Significance: Our observations, together with previous studies that identified oncogenic properties of KLF5, establish the importance of KLF5 activation in human cancers, delineate the varied genomic mechanisms underlying this occurrence, and nominate KLF5 as a putative target for therapeutic intervention in cancer. Cancer Discov; 8(1); 108–25. ©2017 AACR.
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Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis
Authors: Piao Limei , Zhao Guangxian , Zhu Enbo , Inoue Aiko , Shibata Rei , Lei Yanna , Hu Lina , Yu Chenglin , Yang Guang , Wu Hongxian , Xu Wenhu , Okumura Kenji , Ouchi Noriyuki , Murohara Toyoaki , Kuzuya Masafumi , Cheng Xian Wu 
Published: September 2017

Background

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase‐4 (
DPP
4) regulates several intracellular signaling pathways associated with the glucagon‐like peptide‐1 (
GLP
‐1) metabolism, we investigated the role of
DPP
4/
GLP
‐1 axis in vascular senescence and ischemia‐induced neovascularization in mice under chronic stress, with a special focus on adiponectin ‐mediated peroxisome proliferator activated receptor‐γ/its co‐activator 1α (
PGC
‐1α) activation.

Methods and Results

Seven‐week‐old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood‐flow ratio throughout the follow‐up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle
DPP
4 and decreased levels of
GLP
‐1 and adiponectin in plasma and phospho‐
AMP
‐activated protein kinase α (p‐
AMPK
α), vascular endothelial growth factor, peroxisome proliferator activated receptor‐γ,
PGC
‐1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial
CD
31
+
/c‐Kit
+
progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting.
DPP
4 inhibition and
GLP
‐1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion.

Conclusions

These results indicate that the
DPP
4/
GLP
‐1‐adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions.
El book or the libro? Insights from acceptability judgments into determiner/noun code-switches
Authors: Parafita Couto Maria Carmen , Stadthagen-Gonzalez Hans 
Published: September 2017

Objectives/research questions: We used two types of acceptability judgments to experimentally test the predictions of two theoretical models of code-switching regarding the surface realization of the determiner in nominal constructions: lexicalist approaches within the Minimalist Program (MP) versus the Bilingual NP Hypothesis within the Matrix Language Frame Model (MLF). Methodology: Two separate groups of 40 early Spanish-English bilinguals evaluated the acceptability of sentences with code-switches between the determiner and the noun that reflected the predictions of the MP model, the MLF, of both or none. The first group rated them on a Likert scale, while the second group performed a two-alternative forced-choice acceptability task (2AFC). Data and analysis: Ratings from the Likert ratings were subjected to an analysis of variance while results from the 2AFC were analyzed using Thurstone’s Law of Comparative Judgment. Conclusions: Both experiments yielded converging evidence supporting the predictions of the MLF. Results from the 2AFC provided a more detailed picture that suggests also a (smaller) contribution of the language of the determiner. Originality: This is the first study to use acceptability judgments to directly contrast the predictions of these major theoretical models regarding switches between determiner and noun. An additional novelty is the use of the 2AFC and Thurstone’s Law of Comparative Judgment, which yielded a more detailed picture than the more commonly used Likert-scale ratings. Implications: Our results provide further support for Eppler, Luescher, and Deuchar’s recent claim that we can only advance our understanding of grammaticality in code-switching if we combine the insights of the different frameworks rather than considering them in isolation.
Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications
Authors: Babushok Daria V. , Duke Jamie L. , Xie Hongbo M. , Stanley Natasha , Atienza Jamie , Perdigones Nieves , Nicholas Peter , Ferriola Deborah , Li Yimei , Huang Hugh , Ye Wenda , Morrissette Jennifer J. D. , Kearns Jane , Porter David L. , Podsakoff Gregory M. , Eisenlohr Laurence C. , Biegel Jaclyn A. , Chou Stella T. , Monos Dimitrios S. , Bessler Monica , Olson Timothy S. 
Published: September 2017

Key Points
Somatic HLA class I gene mutations are frequent in aAA and define HLA class I restricted autoimmunity in aAA. HLA alleles targeted by inactivating mutations are overrepresented in aAA and correlate with poor therapy response and clonal evolution.
Prevalence of mental health conditions and relationship with
general health in a whole-country population of people with intellectual
disabilities compared with the general population
Authors: Hughes-McCormack Laura A. , Rydzewska Ewelina , Henderson Angela , MacIntyre Cecilia , Rintoul Julie , Cooper Sally-Ann 
Published: September 2017

BackgroundThere are no previous whole-country studies on mental health and
relationships with general health in intellectual disability populations;
study results vary.AimsTo determine the prevalence of mental health conditions and relationships
with general health in a total population with and without intellectual
disabilities.MethodNinety-four per cent completed Scotland's Census 2011. Data on
intellectual disabilities, mental health and general health were
extracted, and the association between them was investigated.ResultsA total of 26 349/5 295 403 (0.5%) had intellectual disabilities. In
total, 12.8% children, 23.4% adults and 27.2% older adults had mental
health conditions compared with 0.3, 5.3 and 4.5% of the general
population. Intellectual disabilities predicted mental health conditions;
odds ratio (OR)=7.1 (95% CI 6.8–7.3). General health was substantially
poorer and associated with mental health conditions; fair health OR=1.8
(95% CI 1.7–1.9), bad/very bad health OR=4.2 (95% CI 3.9–4.6).ConclusionsThese large-scale, whole-country study findings are important, given the
previously stated lack of confidence in comparative prevalence results,
and the need to plan services accordingly.