bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterior reperfusion T-waves: Wellens' syndrome of the posterior wall
Authors: Driver Brian E , Shroff Gautam R , Smith Stephen W 
Published: July 2016

BackgroundReperfusion after coronary occlusion (myocardial infarction, MI), as in Wellens' syndrome, is often represented on ECG as T-wave inversion in the leads overlying the affected myocardial wall(s). As an extension of this logic, reperfusion of the posterior wall should manifest on right precordial leads (which are opposite the posterior wall) as enlarged T-waves.ObjectiveWe sought to determine whether T-wave amplitude (TWa) in leads V2 and V3 after reperfusion in posterior MI (PMI) is greater than in patients without PMI.MethodsReview of ECGs from patients with ST elevation MI of the left circumflex or right coronary artery with post-procedure thrombolysis in MI (TIMI) flow >0 between 2007 and 2009. Blinded experts reviewed admission ECGs to determine the presence of PMI and measure TWa before and after reperfusion. Maximum TWa in V2 and V3 and the difference between maximum and admission V2 and V3 TWa were compared between those with and without PMI.ResultsOf 72 patients, 48 had PMI. Values expressed are medians and IQRs. Maximum TWa after reperfusion was greater in PMI than in non-PMI in V2 (5.00 mm (3.5 to 8.25) vs 3.9 mm (2.75 to 5.5), p=0.04), but not in V3 (4.0 mm (2 to 5.5) vs 3.0 mm (1.75 to 4), p=0.09). The increase in TWa in V2 and V3 after reperfusion was greater in PMI compared with non-PMI: (V2, 3.4 mm (2 to 5.25) vs 1.25 mm (−0.25 to 2), p=0.0005; V3, 2 mm (−0.5 to 3.25) vs 0.25 mm (−1 to 1.75), p=0.03).ConclusionsReperfusion of the posterior wall results in higher right precordial TWa, and an even greater increase in TWa, as measured in leads V2 and V3. This observation has important implications for emergency physicians to accurately identify recent posterior infarction in patients who may be symptom free on presentation but at risk of reocclusion.
Life expectancy of different ethnic groups using death records linked to population census data for 4.62 million people in Scotland
Authors: Gruer Laurence , Cézard Geneviève , Clark Esta , Douglas Anne , Steiner Markus , Millard Andrew , Buchanan Duncan , Katikireddi Srinivasa Vittal , Sheikh Aziz , Bhopal Raj 
Published: July 2016

BackgroundFew countries record the data needed to estimate life expectancy by ethnic group. Such information is helpful in assessing the extent of health inequality.MethodLife tables were created using 3 years of deaths (May 2001–April 2004) linked to Scottish 2001 Census data for 4.62 million individuals with self-reported ethnicity. We created 8 ethnic groups based on the census definitions, each with at least 5000 individuals and 40 deaths. Life expectancy at birth was calculated using the revised Chiang method.ResultsThe life expectancy of White Scottish males at birth was 74.7 years (95% CI 74.6 to 74.8), similar to Mixed Background (73.0; 70.2 to 75.8) and White Irish (75.0; 74.0 to 75.9), but shorter than Indian (80.9; 78.4 to 83.4), Pakistani (79.3; 76.9 to 81.6), Chinese (79.0; 76.5 to 81.5), Other White British (78.9; 78.6 to 79.2) and Other White (77.2; 76.4 to 78.1). The life expectancy of White Scottish females was 79.4 years (79.3 to 79.5), similar to mixed background (79.3; 76.6 to 82.0), but shorter than Pakistani (84.6; 82.0 to 87.3), Chinese (83.4; 81.1 to 85.7), Indian (83.3; 80.7 to 85.9), Other White British (82.6; 82.3 to 82.9), other White (82.0; 81.3 to 82.8) and White Irish (81; 80.2 to 81.8).ConclusionsMales and females in most of the larger ethnic minority groups in Scotland have longer life expectancies than the majority White Scottish population.
Verapamil eluting stents as a possible treatment for vasospasm after subarachnoid hemorrhage
Authors: Bhambri Pallavi , Sarvi Ali , Wong John H , Sundararaj Uttandaraman , Mitha Alim P 
Published: July 2016

ObjectiveThe only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm.MethodsNitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days.ResultsElectrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase.ConclusionsDevelopment of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage.
The long-term effect of bundle care for catheter-related blood stream infection: 5-year follow-up
Authors: Hsin Ho-Tsung , Hsu Meng-Shiuan , Shieh Jiann-Shing 
Published: July 2016

ABSTRACTObjectiveTo address the importance of bundle care for catheter-related infection (CRBSI) on the basis of long-term observation in a catheter-abundant cardiovascular intensive care unit (CVICU).DesignProspective longitudinal cohort study.SettingCVICU of a tertiary referring medical centre in northern Taiwan.ParticipantsAround 1400 critically ill patients annually for 5 years in the CVICU (from January 2010 to June 2015). CRBSI bundle care has been applied ever since by a multidisciplinary team.Main outcome measuresCRBSI per 1000 catheter days, bloodstream infection (BSI) per 1000 inpatient days, and catheter utilisation rates.ResultsFrom January 2010 to June 2015 (22 quarters), there were in total 45 140 inpatient days and 24 163 catheter days, with an overall central venous catheter utilisation rate of 53.5%. The duration of the indwelled catheter was 6.3±1.2 days. The beginning CRBSI rate was 7.0 per 1000 catheter days and was significantly decreased to 0.7 per 1000 catheter days (p&lt;0.001). Regarding the time series, cubic polynomial function depicted the CRBSI decrement most vividly (R2=0.501, p=0.005). In addition, the improvement in overall BSIs (2010 Q1, 4.4 per 1000 inpatient days to 2015 Q2, 0.5 per 1000 inpatient days, p&lt;0.001) significantly correlated with the decrease in CRBSI (r=0.86, p&lt;0.001).ConclusionsThrough the bundle care, we successfully reduced CRBSIs. After 5 years of follow-up, we observed that the effect of bundle care was stepwise and persistent, as long as we kept working on this integrated project.
A simulation study on the hydrogen storage properties of fullerene family molecules Cx(x = 56,60,70) and their hydrides
Authors: Dai Wei , Xiao Ming , Chen Mu-Qing , Xu Jia-Jing , Tang Yong-Jian 
Published: August 2016

Hydrogen storage is a key factor for the application of hydrogen energy. From first principle calculation, we have acquired the energy barrier for hydrogen molecules to pass through the hexagonal rings and pentagonal rings of the fullerene. Then the absorption energy and energy barrier are used to analyze the hydrogen adsorption capacity of the fullerene family and their hydrides. We have also studied the hydrogen storage properties of the fullerene family and their hydrides by grand canonical Monte Carlo method. It is found that the weight density of hydrogen storage at ambient temperature and pressure can reach 7.71 wt.%. The results show that it is difficult for hydrogen to get into the carbon cage of the fullerene because of the high energy barrier, while it is beneficial to destroy the fullerene structure for the processes of absorption and desorption. Meanwhile, fullerene hydrogenation is an effective method to improve the hydrogen storage properties. Our study facilitates the design and synthesis of hydrogen storage materials, and provides theoretical support to improve the hydrogen storage capability for materials.
Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome
Authors: Pitt Jonathan M. , Vétizou Marie , Waldschmitt Nadine , Kroemer Guido , Chamaillard Mathias , Boneca Ivo Gomperts , Zitvogel Laurence 
Published: July 2016

Abstract
The equilibrium linking the intestinal microbiota, the intestinal epithelium, and the host immune system establishes host health and homeostasis, with perturbations of this balance resulting in chronic inflammatory and autoimmune immunopathologies. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. This new evidence hints that interindividual differences in the microbiome may account for the significant heterogeneity in therapeutic and immunopathologic responses to immune checkpoint therapies. We discuss how this new understanding could improve the therapeutic coverage of immune checkpoint inhibitors, and potentially limit their immune-mediated toxicity, through the use of adjunctive “oncomicrobiotics” that indirectly promote beneficial immune responses through optimizing the gut microbiome. Cancer Res; 76(16); 4602–7. ©2016 AACR.
Mechanism-Based Drug Combinations with the DNA Strand–Breaking Nucleoside Analog CNDAC
Authors: Liu Xiaojun , Jiang Yingjun , Nowak Billie , Hargis Sarah , Plunkett William 
Published: July 2016

AbstractCNDAC (2′-C-cyano-2′-deoxy-1-β-d-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematologic malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use. The ability of each agent to decrease proliferative potential, determined by clonogenic assays, was determined in paired cell lines proficient and deficient in certain DNA repair proteins. Subsequently, each agent was used in combination with CNDAC at fixed concentration ratios. The clonogenicity was quantitated by median effect analysis, and a combination index was calculated. The c-Abl kinase inhibitor imatinib had synergy with CNDAC in HCT116 cells, regardless of p53 status. Inhibitors of PARP1 that interfere with homologous recombination (HR) repair or base excision repair (BER) and agents such as temozolomide that cause DNA damage repaired by the BER pathway were also synergistic with CNDAC. The toxicity of the nitrogen mustards bendamustine and cytoxan, or of platinum compounds, which generate DNA adducts repaired by nucleotide excision repair and HR, was additive with CNDAC. An additive cell killing was also achieved by the combination of CNDAC with taxane mitotic inhibitors (paclitaxel and docetaxel). At concentrations that allow survival of the majority of wild-type cells, the synergistic or additive combination effects were selective in HR-deficient cells. This study provides mechanistic rationales for combining CNDAC with other active drugs. Mol Cancer Ther; 15(10); 2302–13. ©2016 AACR.
ERBB2 Overexpression Establishes ERBB3-Dependent Hypersensitivity of Breast Cancer Cells to Withaferin A
Authors: Liu Wenjun , Barnette Annalise R. , Andreansky Samita , Landgraf Ralf 
Published: July 2016

Abstract
The catalytically deficient ERBB3 strongly synergizes with the receptor tyrosine kinase ERBB2, and elevated levels represent an overall risk factor for unfavorable disease outcomes in breast cancer. Although itself not a target of pan-ERBB kinase inhibitors, it contributes to resistance in ERBB2-targeted treatment regiments. The steroidal lactone Withaferin A (WA) has established broad anticancer properties through several modes of action and was shown to be effective against triple-negative breast cancers at elevated concentrations. We found that ERBB2 overexpression does render cells hypersensitive to WA. Although ERBB2 downregulation is one aspect of WA treatment at high concentrations, it is not causal for the elevated sensitivity at lower dosages. Instead, WA targets the ability of ERBB3 to amplify ERBB2 signaling. ERBB3 receptor levels, constitutive phosphorylation of both ERBB3 and ERBB2, as well as signaling through AKT are eliminated by WA treatment. By targeting ERBB2/ERBB3 as a functional unit, it is also effective in cases in which ERBB2-directed inhibitors, such as lapatinib, alone show reduced potency. Hence, WA or derivatives thereof may present a low toxicity addition to ERBB2-targeting therapeutics, especially in cases in which ERBB3 involvement is driving resistance or reduced overall sensitivity. Mol Cancer Ther; 15(11); 2750–7. ©2016 AACR.
The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma
Authors: Olsson P. Olof , Gustafsson Renata , in 't Zandt René , Friman Tomas , Maccarana Marco , Tykesson Emil , Oldberg Åke , Rubin Kristofer , Kalamajski Sebastian 
Published: July 2016

Abstract
A typical obstacle to cancer therapy is the limited distribution of low molecular weight anticancer drugs within the carcinoma tissue. In experimental carcinoma, imatinib (STI571) increases efficacy of synchronized chemotherapy, reduces tumor interstitial fluid pressure, and increases interstitial fluid volume. STI571 also increases the water-perfusable fraction in metastases from human colorectal adenocarcinomas. Because the mechanism(s) behind these effects have not been fully elucidated, we investigated the hypothesis that STI571 alters specific properties of the stromal extracellular matrix. We analyzed STI571-treated human colorectal KAT-4/HT-29 experimental carcinomas, known to have a well-developed stromal compartment, for solute exchange and glycosaminoglycan content, as well as collagen content, structure, and synthesis. MRI of STI571-treated KAT-4/HT-29 experimental carcinomas showed a significantly increased efficacy in dynamic exchanges of solutes between tumor interstitium and blood. This effect was paralleled by a distinct change of the stromal collagen network architecture, manifested by a decreased average collagen fibril diameter, and increased collagen turnover. The glycosaminoglycan content was unchanged. Furthermore, the apparent effects on the stromal cellular composition were limited to a reduction in an NG2-positive stromal cell population. The current data support the hypothesis that the collagen network architecture influences the dynamic exchanges of solutes between blood and carcinoma tissue. It is conceivable that STI571 reprograms distinct nonvascular stromal cells to produce a looser extracellular matrix, ultimately improving transport characteristics for traditional chemotherapeutic agents. Mol Cancer Ther; 15(10); 2455–64. ©2016 AACR.
In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice
Authors: Song Yinhong , Liu Yalan , Hu Rong , Su Min , Rood Debra , Lai Laijun 
Published: July 2016

Abstract
Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs, and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer. Mol Cancer Ther; 15(10); 2413–21. ©2016 AACR.
Targeting Homologous Recombination by Pharmacological Inhibitors Enhances the Killing Response of Glioblastoma Cells Treated with Alkylating Drugs
Authors: Berte Nancy , Piée-Staffa Andrea , Piecha Nadine , Wang Mengwan , Borgmann Kerstin , Kaina Bernd , Nikolova Teodora 
Published: July 2016

Abstract
Malignant gliomas exhibit a high level of intrinsic and acquired drug resistance and have a dismal prognosis. First- and second-line therapeutics for glioblastomas are alkylating agents, including the chloroethylating nitrosoureas (CNU) lomustine, nimustine, fotemustine, and carmustine. These agents target the tumor DNA, forming O6-chloroethylguanine adducts and secondary DNA interstrand cross-links (ICL). These cross-links are supposed to be converted into DNA double-strand breaks, which trigger cell death pathways. Here, we show that lomustine (CCNU) with moderately toxic doses induces ICLs in glioblastoma cells, inhibits DNA replication fork movement, and provokes the formation of DSBs and chromosomal aberrations. Since homologous recombination (HR) is involved in the repair of DSBs formed in response to CNUs, we elucidated whether pharmacologic inhibitors of HR might have impact on these endpoints and enhance the killing effect. We show that the Rad51 inhibitors RI-1 and B02 greatly ameliorate DSBs, chromosomal changes, and the level of apoptosis and necrosis. We also show that an inhibitor of MRE11, mirin, which blocks the formation of the MRN complex and thus the recognition of DSBs, has a sensitizing effect on these endpoints as well. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of CCNU on tumor growth. The data suggest that pharmacologic inhibition of HR, for example by RI-1, is a reasonable strategy for enhancing the anticancer effect of CNUs. Mol Cancer Ther; 15(11); 2665–78. ©2016 AACR.
FLIP: A Targetable Mediator of Resistance to Radiation in Non–Small Cell Lung Cancer
Authors: McLaughlin Kylie A. , Nemeth Zsuzsanna , Bradley Conor A. , Humphreys Luke , Stasik Izabela , Fenning Catherine , Majkut Joanna , Higgins Catherine , Crawford Nyree , Holohan Caitriona , Johnston Patrick G. , Harrison Timothy , Hanna Gerard G. , Butterworth Karl T. , Prise Kevin M. , Longley Daniel B. 
Published: July 2016

AbstractResistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non–small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were downregulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the antitumor activity of IR in vivo. Therefore, FLIP downregulation induced by HDAC inhibitors is a potential clinical strategy to radiosensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR. Mol Cancer Ther; 15(10); 2432–41. ©2016 AACR.
Impact of Increased Early Statin Administration on Ischemic Stroke Outcomes: A Multicenter Electronic Medical Record Intervention
Authors: Flint Alexander C. , Conell Carol , Klingman Jeff G. , Rao Vivek A. , Chan Sheila L. , Kamel Hooman , Cullen Sean P. , Faigeles Bonnie S. , Sidney Steve , Johnston S. Claiborne 
Published: July 2016

Background
Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization.

Methods and Results

This is a retrospective analysis of a multicenter electronic medical record (
EMR
) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke
EMR
order set was modified from an “opt‐in” to “opt‐out” mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time‐series modeling. The
EMR
intervention increased both overall in‐hospital statin administration (from 87.2% to 90.7%,
P
<0.001) and early statin administration (from 16.9% to 26.3%,
P
<0.001). ARIMA models showed a small increase in the rate of survival (difference in probability [
P
diff
]=0.02,
P
=0.016) and discharge to home or rehabilitation facility (
P
diff
=0.04,
P
=0.034) associated with the intervention. The increase in statin administration <8 hours was associated with much larger increases in survival (
P
diff
=0.17,
P
=0.033) and rate of discharge to home or rehabilitation (
P
diff
=0.29,
P
=0.011), as well as a decreased rate of neurological deterioration in‐hospital (
P
diff
=−0.14,
P
=0.026).

Conclusions

A simple
EMR
change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first
EMR
intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.