bluuebunny/crossref_metadata_2025_split huggingface dataset:
A unit-based intervention aimed at improving patient adherence to pharmacological thromboprophylaxis
Authors: Baillie Charles Alexander , Guevara James P , Boston Raymond C , Hecht Todd E H 
Published: June 2015

BackgroundPharmacological thromboprophylaxis is necessary among many hospitalised patients to prevent venous thromboembolism (VTE). However, a significant number of clinician-ordered doses are not administered with many doses refused by patients. We aimed to assess the impact and sustainability of a multifaceted intervention to improve medication adherence to pharmacological thromboprophylaxis. The intervention included a standardised nursing response to patient refusal, daily assessment of VTE prophylaxis usage and regular feedback on refusal rates.MethodsWe conducted a quasi-experimental study of patients admitted between January 2010 and November 2012 to one of six hospital intervention units (three medical and three oncology units) or five control units. The primary outcome was the proportion of VTE prophylaxis doses missed for any reason.ResultsA total of 20 208 admissions occurred at the six hospital units during the study period. In the pre-post analysis, the rate of missed and refused doses decreased significantly after the intervention (24.7% to 14.7% and 18.3% to 9.4%, respectively; p value <0.01 for both comparisons). In multiple regression models with interrupted time series analysis, the intervention was associated with an immediate and sustained decrease in missed (adjusted OR 0.64; 95% CI 0.55 to 0.74 and 0.98; 95%CI 0.97 to 0.99) and refused doses (adjusted OR per month 0.58; 95% CI 0.48 to 0.71 and 0.97; 95%CI 0.96 to 0.98). No immediate or sustained reduction in missed or refused doses was observed in the control units.ConclusionsImplementation of a multifaceted intervention resulted in an immediate and sustained decrease in the proportion of missed and refused doses of pharmacological thromboprophylaxis. Efforts aimed at increasing patient adherence are a promising approach to improve rates of VTE thromboprophylaxis administration.
Connecting cyto-nano-architectural attributes and epithelial molecular expression in oral submucous fibrosis progression to cancer
Authors: Bag Swarnendu , Pal Mousumi , Chaudhary Amrita , Das Raunak Kumar , Paul Ranjan Rashmi , Sengupta Sanghamitra , Chatterjee Jyotirmoy 
Published: June 2015

ObjectiveProblems in pre-cancer diagnosis complicate cancer theragnosis as well as life expectancy. There is uncertainty regarding malignant transformation of oral submucous fibrosis (OSF), an oral pre-cancer with dysplastic (OSFWD) and non-dysplastic (OSFWT) subtypes. Understanding the structural, molecular and physical aspects of epithelial homeostasis may be useful.Materials and methodsHistopathological grading of biopsy sections was performed using H&E staining. Alterations in epithelial surface architecture in different groups was evaluated using scanning electron microscopy (SEM). The expression of crucial epithelial genes (p63, CK-5/6, CK-10, E-cadherin and β-catenin) was studied by immunohistochemistry, Western blot and RT-PCR analysis.ResultsSEM observations revealed that the surface epithelial ridge pattern became thick and dense, and pit pattern gradually decreased in OSFWD and oral squamous cell carcinoma (OSCC). p63, ΔNp63 and CK-5/6 were up-regulated in OSFWD and OSCC but down-regulated in OSFWT. CK-10 was down-regulated in OSFWD compared to OSFWT. Cytoplasmic expression of E-cadherin and β-catenin was elevated in dysplastic and cancerous conditions. Moreover, statistical correlation between SEM features (ridges and pits) and molecular attributes demonstrated a significant positive relationship between the ridge-to-pit ratio and p63 population density (r=0.85) and the ridge-to-pit ratio and CK-5/6 intensity (r=0.63).ConclusionsMolecular changes related to epithelial progressive maturation and cellular proliferation are correlated with concomitant alteration of epithelial surface architecture which helps to predict the malignant potentiality of OSF.
Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones
Authors: Gallagher Michael F , Salley Yvonne , Spillane Cathy D , Ffrench Brendan , El Baruni Salah , Blacksheilds Gordon , Smyth Paul , Martin Cara , Sheils Orla , Watson William , O'Leary John J 
Published: June 2015

AimsTargeting the stem cell properties of tumor-initiating cells is an avenue through which cancer treatment may be improved. Before this can be achieved, so-called ‘cancer stem cell’ (CSC) models must be developed and characterized in specific malignancies.MethodsIn this study, holoclone formation assays were used to characterise stem-like molecular signatures in prostate cancer (PCa) cells.ResultsLNCaP and PC3 parent cells were capable of responding to stem cell differentiation morphogen retinoic acid (RA), suggesting the presence of inherent stem-like properties. LNCaP cells, which represent early, androgen-responsive disease, formed holoclones after twenty six days. PC3 cells, which represent advanced, metastatic, castration-resistant disease, formed holoclones after only six days. Holoclones displayed decreased expression of RA-genes, suggesting a more immature, less differentiated phenotype. Gene and microRNA arrays demonstrated that holoclones downregulated a number of stem cell differentiation regulators while displaying enhanced regulation of G2 to M transition and the mitotic spindle checkpoint components of the cell cycle. PC3 holoclones displayed pronounced downregulation of known regulators of osteoblast differentiation from mesenchymal stem cells and Epithelial Mesenchymal Transition.ConclusionsOur results suggest that some PCa cells retain the ability to transition to a more immature state in which differentiation and metastatic mechanisms are suppressed. The highlighting of osteoblast differentiation regulators in this mechanism is particularly notable, considering the propensity of PCa to metastasise to bone.
Optical characterization of Ga2SeS layered crystals by transmission, reflection and ellipsometry
Authors: Isik Mehmet , Gasanly Nizami 
Published: June 2015

Optical properties of [Formula: see text] crystals grown by Bridgman method were investigated by transmission, reflection and ellipsometry measurements. Analysis of the transmission and reflection measurements performed in the wavelength range of 400–1100 nm at room temperature indicated the presence of indirect and direct transitions with 2.28 eV and 2.38 eV band gap energies. Ellipsometry measurements were carried out in the 1.2–6.0 eV spectral region to get information about optical constants, real and imaginary parts of the pseudodielectric function. Moreover, the critical point (CP) analysis of the second derivative spectra of the pseudodielectric constant in the above band gap region was accomplished. The analysis revealed the presence of five CPs with energies of 3.87, 4.16, 4.41, 4.67 and 5.34 eV.
Seismicity of the central Afar rift and implications for Tendaho dam hazards
Authors: Ayele Atalay , Ebinger Cynthia J. , van Alstyne Carolyn , Keir Derek , Nixon Casey W. , Belachew Manahloh , Hammond James O. S. 
Published: June 2015

Abstract

Temporary broadband seismic networks deployed from 2007 to 2011 around the Afar triple junction of the East African Rift System provide insights into seismicity patterns of the actively deforming crust around the 1.86 km
3
impounded lake system behind the Tendaho dam. The observed seismicity correlates well with the active magmatic centres around central Afar. The area around the dam site is characterized by a network of intersecting NNE- and NW-trending faults. Seismicity clusters observed in the specified time interval indicate that both fault sets are active and are potential sources of seismogenic hazards. The dam neighbourhood is naturally active and it is a challenge to associate the observed seismic activity to either a change in magmato-tectonic conditions or attribute it to the influence of reservoir load. It is evident that the dam region experiences high levels of seismic and volcano-tectonic unrest, regardless of the origin of the activity. The spatial overlap of narrow zones of crustal seismicity and upper mantle low velocity zones observed in S-wave tomography models suggests that melt production zones guide the distribution of strain during continental rupture. Given its volcanically and seismically active setting, the Tendaho dam site and the surrounding region require continuous monitoring for the safety of downstream populations and development infrastructures in the Afar National Regional State of Ethiopia.
Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens
Authors: Tveita Anders Aune , Schjesvold Fredrik , Haabeth Ole Audun , Fauskanger Marte , Bogen Bjarne 
Published: June 2015

AbstractTumors cells can escape cytotoxic CD8+ T cells by preventing MHC I display of tumor antigens. It is unknown how tumors evade CD4+ T-cell responses, but because many tumor cells lack MHC II expression, novel mechanisms would be required. We have investigated this issue in a model in which MHC IINEG myeloma cells secrete a monoclonal Ig containing a V region L chain (VL) epitope recognized by CD4+ T cells. Infiltrating macrophages process and present the secreted tumor antigen to Th1 cells, resulting in induction of macrophage cytotoxicity and apparent rejection of the tumor. Despite long-term tumor protection in VL-specific T-cell receptor transgenic mice, we here describe that some myeloma cells persisted in a dormant state and, eventually, formed expanding tumors. Escape tumor cells maintained their secretion of complete (H+L) monoclonal Ig with unchanged sequence, while secretion of surplus free L chain was severely diminished. Although free L chains were efficiently processed and presented by tumor-infiltrating macrophages to CD4+ T cells, complete (H+L) monoclonal Ig was not. Forced overexpression of free L chain secretion reinstated tumor rejection. These results show that tumors can escape CD4+ T-cell–mediated rejection by impairing indirect presentation of tumor antigen by infiltrating macrophages. This occurs through a novel mechanism of immunoediting, in which modulation of the quaternary structure of the secreted tumor-specific antigen reduces its immunogenicity. Cancer Res; 75(16); 3268–78. ©2015 AACR.
Fetal Growth and Subsequent Maternal Risk of Colorectal Cancer
Authors: Crump Casey , Sundquist Jan , Sieh Weiva , Winkleby Marilyn A. , Sundquist Kristina 
Published: June 2015

Abstract
Background: High birth weight has been associated with subsequent increased risk of breast cancer in the infant's mother, possibly related to maternal estrogen and growth factor pathways. However, its association with maternal risk of colorectal cancer, the third most common cancer among women, is unknown.
Methods: We conducted a national cohort study of 1,838,509 mothers who delivered 3,590,523 babies in Sweden in 1973–2008, followed up for colorectal cancer incidence through 2009.
Results: There were 7,318 mothers diagnosed with colorectal cancer in 36.8 million person-years of follow-up. After adjusting for maternal age, body mass index, diabetes, and other potential confounders, high fetal growth was associated with a subsequent increased risk of colorectal cancer in the mother [incidence rate ratio (IRR) per additional 1 SD relative to mean birth weight for gestational age and sex, 1.05; 95% confidence intervals (CI), 1.03–1.07; P &lt; 0.0001]. Each 1,000 g increase in the infant's birth weight was associated with a 12% increase in the mother's subsequent risk of colorectal cancer (IRR, 1.12; 95% CI, 1.07–1.17; P &lt; 0.0001). Multiple gestation was also independently associated with increased maternal risk of colorectal cancer (IRR for twin or higher order vs. singleton, 1.22; 95% CI, 1.04–1.44; P = 0.02).
Conclusion: In this large cohort study, high fetal growth and multiple gestation were independently associated with subsequent higher maternal risk of colorectal cancer. These findings warrant further investigation of maternal growth factor and estrogen pathways in the etiology of colorectal cancer.
Impact: If confirmed, our findings may help identify subgroups of women at high risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(8); 1184–9. ©2015 AACR.
Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations
Authors: Hunter John C. , Manandhar Anuj , Carrasco Martin A. , Gurbani Deepak , Gondi Sudershan , Westover Kenneth D. 
Published: June 2015

Abstract
KRAS mutations are the most common genetic abnormalities in cancer, but the distribution of specific mutations across cancers and the differential responses of patients with specific KRAS mutations in therapeutic clinical trials suggest that different KRAS mutations have unique biochemical behaviors. To further explain these high-level clinical differences and to explore potential therapeutic strategies for specific KRAS isoforms, we characterized the most common KRAS mutants biochemically for substrate binding kinetics, intrinsic and GTPase-activating protein (GAP)–stimulated GTPase activities, and interactions with the RAS effector, RAF kinase. Of note, KRAS G13D shows rapid nucleotide exchange kinetics compared with other mutants analyzed. This property can be explained by changes in the electrostatic charge distribution of the active site induced by the G13D mutation as shown by X-ray crystallography. High-resolution X-ray structures are also provided for the GDP-bound forms of KRAS G12V, G12R, and Q61L and reveal additional insight. Overall, the structural data and measurements, obtained herein, indicate that measurable biochemical properties provide clues for identifying KRAS-driven tumors that preferentially signal through RAF.
Implications: Biochemical profiling and subclassification of KRAS-driven cancers will enable the rational selection of therapies targeting specific KRAS isoforms or specific RAS effectors. Mol Cancer Res; 13(9); 1325–35. ©2015 AACR.
Estrogen Protects against Obesity-Induced Mammary Gland Inflammation in Mice
Authors: Bhardwaj Priya , Du Baoheng , Zhou Xi Kathy , Sue Erika , Giri Dilip , Harbus Michael D. , Falcone Domenick J. , Hudis Clifford A. , Subbaramaiah Kotha , Dannenberg Andrew J. 
Published: June 2015

Abstract
Obesity is a risk factor for the development of hormone receptor (HR)–positive breast cancer in postmenopausal women. Obesity causes subclinical inflammation in white adipose tissue (WAT), characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase. Previously, we demonstrated CLS and elevated levels of proinflammatory mediators and aromatase in the mammary glands of obese mice and breast tissue of obese women. Here, we tested the hypothesis that supplemental estrogen could prevent or reverse WAT inflammation (WATi) and related molecular changes in the mammary gland. C57BL/6J mice were ovariectomized (OVX) to simulate the postmenopausal state. Supplementation with 17β-estradiol (E2) protected against high fat diet (HFD)-induced weight gain and mammary glands WATi. Expression of proinflammatory mediators (Cox-2, TNFα, IL1β) and aromatase were also reduced in the mammary glands of mice that received supplemental E2. Next, to determine whether E2 supplementation can reverse WATi, obese OVX mice were treated with E2 or placebo and then continued on HFD. E2 supplementation induced weight loss, reversed mammary gland inflammation, and downregulated expression of proinflammatory mediators and aromatase. Finally, we determined whether the protective effects of E2 were mediated by estrogen receptor-α (ERα). Knocking out ERα in ovary intact mice fed a HFD led to weight gain, WATi and elevated levels of proinflammatory mediators and aromatase mimicking the effects of OVX. Taken together, our findings indicate that estrogen via ERα protects against weight gain, WATi and associated increases in proinflammatory mediators and aromatase in the mammary gland. Cancer Prev Res; 8(8); 751–9. ©2015 AACR.
NKG2D Receptor and Its Ligands in Host Defense
Authors: Lanier Lewis L. 
Published: June 2015

Abstract
NKG2D is an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, and subsets of CD4+ T cells, invariant NKT cells (iNKT), and γδ T cells. In humans, NKG2D transmits signals by its association with the DAP10 adapter subunit, and in mice alternatively spliced isoforms transmit signals either using DAP10 or DAP12 adapter subunits. Although NKG2D is encoded by a highly conserved gene (KLRK1) with limited polymorphism, the receptor recognizes an extensive repertoire of ligands, encoded by at least eight genes in humans (MICA, MICB, RAET1E, RAET1G, RAET1H, RAET1I, RAET1L, and RAET1N), some with extensive allelic polymorphism. Expression of the NKG2D ligands is tightly regulated at the level of transcription, translation, and posttranslation. In general, healthy adult tissues do not express NKG2D glycoproteins on the cell surface, but these ligands can be induced by hyperproliferation and transformation, as well as when cells are infected by pathogens. Thus, the NKG2D pathway serves as a mechanism for the immune system to detect and eliminate cells that have undergone “stress.” Viruses and tumor cells have devised numerous strategies to evade detection by the NKG2D surveillance system, and diversification of the NKG2D ligand genes likely has been driven by selective pressures imposed by pathogens. NKG2D provides an attractive target for therapeutics in the treatment of infectious diseases, cancer, and autoimmune diseases. Cancer Immunol Res; 3(6); 575–82. ©2015 AACR.
Risk of Heart Failure and Death After Prolonged Smoking Cessation
Authors: Ahmed Amiya A. , Patel Kanan , Nyaku Margaret A. , Kheirbek Raya E. , Bittner Vera , Fonarow Gregg C. , Filippatos Gerasimos S. , Morgan Charity J. , Aban Inmaculada B. , Mujib Marjan , Desai Ravi V. , Allman Richard M. , White Michel , Deedwania Prakash , Howard George , Bonow Robert O. , Fletcher Ross D. , Aronow Wilbert S. , Ahmed Ali 
Published: June 2015

Background—
According to the 2004 Surgeon General’s Report on Health Consequences of Smoking, after >15 years of abstinence, the cardiovascular risk of former smokers becomes similar to that of never-smokers. Whether this health benefit of smoking cessation varies by amount and duration of prior smoking remains unclear.

Methods and Results—
Of the 4482 adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study, 2556 were never-smokers, 629 current smokers, and 1297 former smokers with >15 years of cessation, of whom 312 were heavy smokers (highest quartile; ≥32 pack-years). Age–sex–race–adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for centrally adjudicated incident HF and mortality during 13 years of follow-up were estimated using Cox regression models. Compared with never-smokers, former smokers as a group had similar risk for incident HF (aHR, 0.99; 95% CI, 0.85–1.16) and all-cause mortality (aHR, 1.08; 95% CI, 0.96–1.20), but former heavy smokers had higher risk for both HF (aHR, 1.45; 95% CI, 1.15–1.83) and mortality (aHR, 1.38; 95% CI, 1.17–1.64). However, when compared with current smokers, former heavy smokers had lower risk of death (aHR, 0.64; 95% CI, 0.53–0.77), but not of HF (aHR, 0.97; 95% CI, 0.74–1.28).

Conclusions—
After >15 years of smoking cessation, the risk of HF and death for most former smokers becomes similar to that of never-smokers. Although this benefit of smoking cessation is not extended to those with ≥32 pack-years of prior smoking, they have lower risk of death relative to current smokers.
Wnt/β-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O
Authors: Okada Katsuki , Naito Atsuhiko T. , Higo Tomoaki , Nakagawa Akito , Shibamoto Masato , Sakai Taku , Hashimoto Akihito , Kuramoto Yuki , Sumida Tomokazu , Nomura Seitaro , Ito Masamichi , Yamaguchi Toshihiro , Oka Toru , Akazawa Hiroshi , Lee Jong-Kook , Morimoto Sachio , Sakata Yasushi , Shiojima Ichiro , Komuro Issei 
Published: June 2015

Background—
There are changes in the skeletal muscle of patients with chronic heart failure (CHF), such as volume reduction and fiber type shift toward fatigable type IIb fiber. Forkhead box O (FoxO) signaling plays a critical role in the development of skeletal myopathy in CHF, and functional interaction between FoxO and the Wnt signal mediator β-catenin was previously demonstrated. We have recently reported that serum of CHF model mice activates Wnt signaling more potently than serum of control mice and that complement C1q mediates this activation. We, therefore, hypothesized that C1q-induced activation of Wnt signaling plays a critical role in skeletal myopathy via the interaction with FoxO.

Methods and Results—
Fiber type shift toward fatigable fiber was observed in the skeletal muscle of dilated cardiomyopathy model mice, which was associated with activation of both Wnt and FoxO signaling. Wnt3a protein activated FoxO signaling and induced fiber type shift toward fatigable fiber in C2C12 cells. Wnt3a-induced fiber type shift was inhibited by suppression of FoxO1 activity, whereas Wnt3a-independent fiber type shift was observed by overexpression of constitutively active FoxO1. Serum of dilated cardiomyopathy mice activated both Wnt and FoxO signaling and induced fiber type shift toward fatigable fiber in C2C12 cells. Wnt inhibitor and C1-inhibitor attenuated FoxO activation and fiber type shift both in C2C12 cells and in the skeletal muscle of dilated cardiomyopathy mice.

Conclusions—
C1q-induced activation of Wnt signaling contributes to fiber type shift toward fatigable fiber in CHF. Wnt signaling may be a novel therapeutic target to prevent skeletal myopathy in CHF.