bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between patient experience factors and likelihood of 30-day readmission: a prospective cohort study
Authors: Carter Jocelyn , Ward Charlotte , Wexler Deborah , Donelan Karen 
Published: November 2017

ObjectiveHospital care comprises nearly a third of US healthcare expenditures. Fifteen to 20 per cent of this spending is considered to be potentially preventable. Risk prediction models have suboptimal accuracy and typically exclude patient experience data. No studies have explored patient perceptions of the likelihood of readmission during index admission. Our objective was to examine associations between patient perceptions of care during index hospital admission and 30-day readmission.DesignProspective cohort study.SettingTwo inpatient adult medicine units at Massachusetts General Hospital, Boston, Massachusetts.ParticipantsEight hundred and forty-six patients admitted to study units between January 2012 and January 2016 who met eligibility criteria and consented to enrolment.Main outcomeOdds of 30-day readmission.ResultsOf 1754 eligible participants, 846 (48%) were enrolled and 201 (23.8%) were readmitted within 30 days. Readmitted participants were less likely to have a high school diploma/GED (44.3% not readmitted vs 53.5% readmitted, P=0.02). In multivariable models adjusting for baseline differences, respondents who reported being ‘very satisfied’ with the care received during the index hospitalisation were less likely to be readmitted (adjusted OR 0.61, 95% CI 0.43 to 0.88, P=0.007). Participants reporting doctors ‘always listened to them carefully’ were less likely to be readmitted (adjusted OR 0.68, 95% CI 0.48 to 0.97, P=0.03). Participants reporting they were ‘very likely’ to be readmitted were not more likely to be readmitted (adjusted OR 1.35, 95% CI 0.83 to 2.19, P=0.22).ConclusionParticipants reporting high satisfaction and good provider communication were less likely to be readmitted. Rates of readmission were increased among participants stating they were very likely to be readmitted though this association was not statistically significant. Incorporating patient-reported measures during index hospitalisations may improve readmission prediction.
Obesity and elevated blood pressure in suburban student athletes
Authors: Georgeson Andrew , Lebenthal Mark , Catania Raymond , Georgeson Steven 
Published: November 2017

ObjectiveTo assess the prevalence of obesity and elevated blood pressure in a suburban population of middle school and high school student athletes and examine the differences from the previously published populations.Study designThe Student Athlete Cardiac Evaluation Registry Study is a single-centre, community hospital-based registry study, that provided free annual preparticipation physical examinations (PPE) from 2009 to 2017. The PPE on the 906 athletes included a history, a physical examination and body metrics including height, weight and blood pressure. The blood pressure was measured with an automated blood pressure cuff and, if elevated, was remeasured using a manual blood pressure cuff with aneroid manometer. The data from the PPE were collected and analysed for prevalence of obesity, overweight and elevated blood pressure measurements.ResultsThe prevalence of obesity was 11%, and 19% of participants were overweight. Many of the athletes had an elevated blood pressure (15%). There was a significant association (P<0.001) between weight and elevated blood pressure. Among athletes with elevated blood pressure, 50% were either obese or overweight.ConclusionsThere was a similar prevalence of overweight athletes in our study compared with previously published populations, but there were a lower proportion of obese athletes, which may be explained by differences in demographics. Despite the differences in study populations and the lower rate of obesity, the proportion of athletes with elevated blood pressure in our study was similar to prior populations. Weight issues and elevated blood pressure affect athletes across a range of different populations.
Clinical outcomes in 1731 patients undergoing mitral valve surgery for rheumatic valve disease
Authors: Kim Wan Kee , Kim Ho Jin , Kim Joon Bum , Jung Sung-Ho , Choo Suk Jung , Chung Cheol Hyun , Lee Jae Won 
Published: November 2017

ObjectiveUnlike degenerative mitral valve (MV) disease, the advantages of valve repair procedure over replacement have been debated in rheumatic MV disease. This study aims to evaluate the impact of procedural types on long-term outcomes through analyses on a large data set from an endemic area of rheumatic disease.MethodsWe evaluated 1731 consecutive patients (52.3±12.5 years; 1190 women) undergoing MV surgery for rheumatic MV disease between 1997 and 2015. Long-term survival and valve-related outcomes were compared between repair and replacement procedures. To adjust for selection bias, propensity score analyses were performed.ResultsPatients undergoing repair were younger and had more predominant mitral regurgitation than mechanical and bioprosthetic replacement groups (61.6% vs 15.6% vs 24.4%; P<0.001). During follow-up (130.9±27.7 months), 283 patients (16.3%) died and 256 patients (14.8%) experienced valve-related complications. Propensity score matching yielded 188 pairs of repair and replacement patients that were well balanced for baseline covariates. In the matched cohort, there was no significant difference in the mortality risk between the repair and replacement groups (HR, 1.24; 95% CI 0.62 to 2.48). The risk of composite valve-related complications, however, was significantly lower in repair group (HR, 0.57; 95% CI 0.33 to 0.99) principally derived by a lower risk of haemorrhagic events (HR, 0.23; 95% CI 0.07 to 0.70). The incidence of reoperation was not significantly different between groups in the matched cohort (HR, 1.62; 95% CI 0.49 to 5.28).ConclusionValve repair in well-selected patients with severe rheumatic MV disease led to comparable survival, but superior valve-related outcomes compared with valve replacement surgery.
The NOTCH4–HEY1 Pathway Induces Epithelial–Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
Authors: Fukusumi Takahito , Guo Theresa W. , Sakai Akihiro , Ando Mizuo , Ren Shuling , Haft Sunny , Liu Chao , Amornphimoltham Panomwat , Gutkind J. Silvio , Califano Joseph A. 
Published: November 2017

Abstract
Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood.
Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among NOTCH4, HEY1, and epithelial–mesenchymal transition (EMT)-related genes using the TCGA data set and in vitro assays.
Results: HEY1 is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison with other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, NOTCH4 and HEY1 upregulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression was associated with an EMT phenotype as well as increased invasion and cell migration.
Conclusions: In HNSCC, the NOTCH4–HEY1 pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. Clin Cancer Res; 24(3); 619–33. ©2017 AACR.
Development of a Function-Blocking Antibody Against Fibulin-3 as a Targeted Reagent for Glioblastoma
Authors: Nandhu Mohan S. , Behera Prajna , Bhaskaran Vivek , Longo Sharon L. , Barrera-Arenas Lina M. , Sengupta Sadhak , Rodriguez-Gil Diego J. , Chiocca E. Antonio , Viapiano Mariano S. 
Published: November 2017

Abstract
Purpose: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NFκB signaling.
Experimental Design: We used deletion constructs to identify a key signaling motif of fibulin-3. An mAb (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3. mAb428.2 was tested in cultures to measure its inhibitory effect on fibulin-3 signaling. Nude mice carrying subcutaneous and intracranial GBM xenografts were treated with the maximum achievable dose of mAb428.2 to measure target engagement and antitumor efficacy.
Results: We identified a critical 23-amino acid sequence of fibulin-3 that activates its signaling mechanisms. mAb428.2 binds to that epitope with nanomolar affinity and blocks the ability of fibulin-3 to activate ADAM17, Notch, and NFκB signaling in GBM cells. mAb428.2 treatment of subcutaneous GBM xenografts inhibited fibulin-3, increased tumor cell apoptosis, and enhanced the infiltration of inflammatory macrophages. The antibody reduced tumor growth and extended survival of mice carrying GBMs as well as other fibulin-3–expressing tumors. Locally infused mAb428.2 showed efficacy against intracranial GBMs, increasing tumor apoptosis and reducing tumor invasion and vascularization, which are enhanced by fibulin-3.
Conclusions: To our knowledge, this is the first rationally developed, function-blocking antibody against an ECM target in GBM. Our results offer a proof of principle for using “anti-ECM” strategies toward more efficient targeted therapies for malignant glioma. Clin Cancer Res; 24(4); 821–33. ©2017 AACR.
JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma
Authors: Garcia Patrick L. , Miller Aubrey L. , Gamblin Tracy L. , Council Leona N. , Christein John D. , Arnoletti J. Pablo , Heslin Marty J. , Reddy Sushanth , Richardson Joseph H. , Cui Xiangqin , van Waardenburg Robert C.A.M. , Bradner James E. , Yang Eddy S. , Yoon Karina J. 
Published: November 2017

Abstract
Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of &lt;30%. For a majority of patients, chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the first-line agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ∼8 months. Combining this agent with cisplatin increases survival by ∼3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the antitumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2 and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis and downregulated multiple c-Myc transcriptional targets that regulate cell-cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. Mol Cancer Ther; 17(1); 107–18. ©2017 AACR.
Pharmacologic Inhibition of the Menin–MLL Interaction Leads to Transcriptional Repression of PEG10 and Blocks Hepatocellular Carcinoma
Authors: Kempinska Katarzyna , Malik Bhavna , Borkin Dmitry , Klossowski Szymon , Shukla Shirish , Miao Hongzhi , Wang Jingya , Cierpicki Tomasz , Grembecka Jolanta 
Published: November 2017

Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein–protein interaction between menin and histone methyltransferase mixed lineage leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Here, we demonstrate that the menin–MLL inhibitor MI-503 shows antitumor activity in in vitro and in vivo models of HCC and reveals the potential mechanism of menin contribution to HCC. Treatment with MI-503 selectively kills various HCC cell lines and this effect is significantly enhanced by a combination of MI-503 with sorafenib, the standard-of-care therapy for HCC. Furthermore, MI-503 reduces sphere formation and cell migration in in vitro HCC models. When applied in vivo, MI-503 gives a strong antitumor effect both as a single agent and in combination with sorafenib in mice xenograft models of HCC. Mechanistically, treatment with MI-503 downregulates expression of several genes known to play a critical role in proliferation and migration of HCC cells, including PEG10, and displaces the menin–MLL1 complex from the PEG10 promoter, resulting in reduced H3K4 methylation and transcriptional repression. Overall, our studies reveal a mechanistic link between menin and genes involved in HCC and demonstrate that pharmacologic inhibition of the menin–MLL interaction might represent a promising therapeutic approach for HCC. Mol Cancer Ther; 17(1); 26–38. ©2017 AACR.
CAT-02-106, a Site-Specifically Conjugated Anti-CD22 Antibody Bearing an MDR1-Resistant Maytansine Payload Yields Excellent Efficacy and Safety in Preclinical Models
Authors: Drake Penelope M. , Carlson Adam , McFarland Jesse M. , Bañas Stefanie , Barfield Robyn M. , Zmolek Wesley , Kim Yun Cheol , Huang Betty C.B. , Kudirka Romas , Rabuka David 
Published: November 2017

Abstract
Hematologically derived tumors make up ∼10% of all newly diagnosed cancer cases in the United States. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1. CD22 is a clinically validated target for the treatment of NHL, but no anti-CD22 agents have yet been approved for this indication. Recent approval of an anti-CD22 antibody–drug conjugate (ADC) for the treatment of relapsed/refractory ALL supports the rationale for targeting this protein. An opportunity exists for a next-generation anti-CD22 antibody–drug conjugate (ADC) to address unmet medical needs in the relapsed/refractory NHL population. We describe a site-specifically conjugated antibody–drug conjugate, made using aldehyde tag technology, targeted against CD22 and bearing a noncleavable maytansine payload that is resistant to MDR1-mediated efflux. The construct was efficacious against CD22+ NHL xenografts and could be repeatedly dosed in cynomolgus monkeys at 60 mg/kg with no observed significantly adverse effects. Exposure to total ADC at these doses (as assessed by AUC0-inf) indicated that the exposure needed to achieve efficacy was below tolerable limits. Together, the data suggest that this drug has the potential to be used effectively in patients with CD22+ tumors that have developed MDR1-related resistance to prior therapies. Mol Cancer Ther; 17(1); 161–8. ©2017 AACR.
Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging
Authors: Leenders Geert J. , Smeets Mirjam B. , van den Boomen Maaike , Berben Monique , Nabben Miranda , van Strijp Dianne , Strijkers Gustav J. , Prompers Jeanine J. , Arslan Fatih , Nicolay Klaas , Vandoorne Katrien 
Published: November 2017

Objective—
The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI).

Approach and Results—

Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE
−/−
, and statin-treated ApoE
−/−
mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE
−/−
infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE
−/−
infarcts, indicated by reduced permeability. The infarcted tissue of ApoE
−/−
mice 3 days post-MI displayed an unbalanced
Vegfa
(vascular endothelial growth factor A)/
Angpt1
(angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45
+
leukocytes and inflammatory LY6C
hi
monocytes. Statins reversed the unbalanced
Vegfa/Angpt1
expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE
−/−
mice.

Conclusions—
Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.
Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure
Authors: Van Tassell Benjamin W. , Canada Justin , Carbone Salvatore , Trankle Cory , Buckley Leo , Oddi Erdle Claudia , Abouzaki Nayef A. , Dixon Dave , Kadariya Dinesh , Christopher Sanah , Schatz Aaron , Regan Jessica , Viscusi Michele , Del Buono Marco , Melchior Ryan , Mankad Pranav , Lu Juan , Sculthorpe Robin , Biondi-Zoccai Giuseppe , Lesnefsky Edward , Arena Ross , Abbate Antonio 
Published: November 2017

Background
An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF.

Methods and Results

We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo. Patients underwent measurement of peak oxygen consumption (V
o
2
[mL/kg per minute]) and ventilatory efficiency (the VE/V
co
2
slope). Treatment with anakinra did not affect peak V
o
2
or VE/V
co
2
slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak V
o
2
from 14.5 (10.5–16.6) mL/kg per minute to 16.1 (13.2–18.6) mL/kg per minute (
P
=0.009 for within-group changes), whereas no significant changes occurred within the anakinra 2-week or placebo groups. The between-groups differences, however, were not statistically significant. The incidence of death or rehospitalization for HF at 24 weeks was 6%, 31%, and 30%, in the anakinra 12-week, anakinra 2-week, and placebo groups, respectively (log-rank test
P
=0.10).

Conclusions

No change in peak V
o
2
occurred at 2 weeks in patients with recently decompensated systolic HF treated with anakinra, whereas an improvement was seen in those patients in whom anakinra was continued for 12 weeks. Additional larger studies are needed to validate the effects of prolonged anakinra on peak V
o
2
and rehospitalization for HF.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01936909.
Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion
Authors: Wei Daniel , Oxley Thomas J. , Nistal Dominic A. , Mascitelli Justin R. , Wilson Natalie , Stein Laura , Liang John , Turkheimer Lena M. , Morey Jacob R. , Schwegel Claire , Awad Ahmed J. , Shoirah Hazem , Kellner Christopher P. , De Leacy Reade A. , Mayer Stephan A. , Tuhrim Stanley , Paramasivam Srinivasan , Mocco J , Fifi Johanna T. 
Published: November 2017

Background and Purpose—
Endovascular recanalization treatment for acute ischemic stroke is a complex, time-sensitive intervention. Trip-and-treat is an interhospital service delivery model that has not previously been evaluated in the literature and consists of a shared mobile interventional stroke team that travels to primary stroke centers to provide on-site interventional capability. We compared treatment times between the trip-and-treat model and the traditional drip-and-ship model.

Methods—
We performed a retrospective analysis on 86 consecutive eligible patients with acute ischemic stroke secondary to large vessel occlusion who received endovascular treatment at 4 hospitals in Manhattan. Patients were divided into 2 cohorts: trip-and-treat (n=39) and drip-and-ship (n=47). The primary outcome was initial door-to-puncture time, defined as the time between arrival at any hospital and arterial puncture. We also recorded and analyzed the times of last known well, IV-tPA (intravenous tissue-type plasminogen activator) administration, transfer, and reperfusion.

Results—

Mean initial door-to-puncture time was 143 minutes for trip-and-treat and 222 minutes for drip-and-ship (
P
<0.0001). Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (
P
=0.0887), initial door-to-recanalization was nonetheless 79 minutes faster for trip-and-treat (
P
<0.0001). There was a trend in improved admission-to-discharge change in National Institutes of Health Stroke Scale for trip-and-treat compared with drip-and-ship (
P
=0.0704).

Conclusions—
Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.
Fundamentals of the Real Estate Legislative System and Its Impact on Sustainable Development: Dubai Case Study
Authors: Jadalhaq Iyad Mohammed 
Published: November 2017

Abstract
The real estate legislative system is one of the bases of the sustainable development process. This research focuses on the role of the legal system in sustainable development, according to the most prominent relevant international reports. The uae ranked forty-first globally in the Human Development Index (hdi). In the World Bank’s ‘Doing Business Report’, the uae ranked second globally and first in the Middle East and North Africa (mena) for the ‘Dealing with Construction Permits’ indicator. Thus, the Emirate of Dubai is deemed the second-best city in the world in terms of ease of dealing with construction permits. For the ‘Registering Property’ indicator, the uae ranked tenth globally and first in the Middle East and North Africa (mena). Despite the uae’s great achievements in terms of developmental ranking at the global level, there is still more to achieve in the field of development.