bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal exposure to hurricane destruction and fetal mortality
Authors: Zahran Sammy , Breunig Ian M , Link Bruce G , Snodgrass Jeffrey G , Weiler Stephan , Mielke Howard W 
Published: May 2014

BackgroundThe majority of research documenting the public health impacts of natural disasters focuses on the well-being of adults and their living children. Negative effects may also occur in the unborn, exposed to disaster stressors when critical organ systems are developing and when the consequences of exposure are large.MethodsWe exploit spatial and temporal variation in hurricane behaviour as a quasi-experimental design to assess whether fetal death is dose-responsive in the extent of hurricane damage. Data on births and fetal deaths are merged with Parish-level housing wreckage data. Fetal outcomes are regressed on housing wreckage adjusting for the maternal, fetal, placental and other risk factors. The average causal effect of maternal exposure to hurricane destruction is captured by difference-in-differences analyses.ResultsThe adjusted odds of fetal death are 1.40 (1.07–1.83) and 2.37 (1.684–3.327) times higher in parishes suffering 10–50% and >50% wreckage to housing stock, respectively. For every 1% increase in the destruction of housing stock, we observe a 1.7% (1.1–2.4%) increase in fetal death. Of the 410 officially recorded fetal deaths in these parishes, between 117 and 205 may be attributable to hurricane destruction and postdisaster disorder. The estimated fetal death toll is 17.4–30.6% of the human death toll.ConclusionsThe destruction caused by Hurricanes Katrina and Rita imposed significant measurable losses in terms of fetal death. Postdisaster migratory dynamics suggest that the reported effects of maternal exposure to hurricane destruction on fetal death may be conservative.
Rupture Resemblance Score (RRS): toward risk stratification of unruptured intracranial aneurysms using hemodynamic–morphological discriminants
Authors: Xiang Jianping , Yu Jihnhee , Choi Hoon , Dolan Fox Jennifer M , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H , Meng Hui 
Published: May 2014

ObjectiveWe have previously developed three logistic regression models for discriminating intracranial aneurysm rupture status from 119 aneurysms based on hemodynamic–morphological parameters. In this study we exploit their use as a tool for predicting the risk of rupture of aneurysms with a defined Rupture Resemblance Score (RRS).MethodsWe collected three-dimensional images of 85 consecutive aneurysms, applied the three regression models and compared model performance at predicting rupture status against anecdotal metrics (aneurysm size and aspect ratio). We then reinterpreted the model-predicted probability as RRS, where the higher the score the closer the resemblance to previously known rupture components, and applied the RRS prospectively to four unruptured aneurysms with borderline treatment decisions.ResultsAll three models yielded excellent sensitivity (0.78–0.83) and specificity (0.78–0.84) at a cutoff score of 50%, whereas aneurysm size and aspect ratio showed poor sensitivities (0.28 and 0.33, respectively). Lowering the cutoff score to 30% improved sensitivity to 0.90. The RRS identified most of the ruptured aneurysms and also some unruptured ones that closely resembled ruptured aneurysms hemodynamically and/or morphologically. The prospective application of the RRS to unruptured aneurysms shows that it could provide additional insights for treatment decisions.ConclusionsPrevious regression models based on hemodynamic–morphological parameters are able to discriminate rupture in a new cohort in the same population. A higher probability of rupture is associated with larger size ratio, lower normalized wall shear stress and higher oscillatory shear index. The RRS could potentially stratify rupture risk and assist in treatment decision-making for unruptured aneurysms.
Results of a national cerebrovascular neurosurgery survey on the management of cerebral vasospasm/delayed cerebral ischemia
Authors: Bulsara Ketan R , Günel Murat , Amin-Hanjani Sepideh , Chen Peng Roc , Connolly E Sander , Friedlander Robert M 
Published: May 2014

ObjectiveFollowing aneurysmal subarachnoid hemorrhage, cerebral vasospasm/delayed cerebral ischemia accounts for significant morbidity and mortality. In this paper we provide the first glimpse of actual practice in the management of cerebral vasospasm in the USA.MethodsAll active members of the Joint American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Cerebrovascular Section were emailed the survey. The responses were collected anonymously.ResultsThe response rate for this survey was 44% (177 responses/400 total members). Non-responders were characterized by the fact that multiple responders were not obtained from practices that had multiple providers with uniform practice. Both high-volume and low-volume centers were equally represented. Optimizing medical management is first-line treatment in practice. Although there is some variability regarding screening methods, the greatest variability occurs with regard to the choice of intra-arterial treatment drug and dose. There is also considerable variability in the perceived effectiveness of endovascular treatment for vasospasm.ConclusionsIn this preliminary glimpse of actual cerebral vasospasm management practice in the USA, two salient points emerge: (1) there is considerable variability in intra-arterial therapies for vasospasm; and (2) there are major differences in the perceived effectiveness of these therapies. Standardization of intra-arterial therapies may contribute to improved outcomes. A prospective randomized trial evaluating endovascular treatment for cerebral vasospasm is needed.
Experimental observations of mechanical dilation at the onset of gas flow in Callovo-Oxfordian claystone
Authors: Cuss Robert , Harrington Jon , Giot Richard , Auvray Christophe 
Published: May 2014

Abstract
Understanding the mechanisms controlling the advective movement of gas and its potential impact on a geological disposal facility (GDF) for radioactive waste is important to performance assessment. In a clay-based GDF, four primary phenomenological models can be defined to describe gas flow: (i) diffusion and/or solution within interstitial water; (ii) visco-capillary (or two-phase) flow in the original porosity of the fabric; (iii) flow along localized dilatant pathways (micro-fissuring); and (iv) gas fracturing of the rock. To investigate which mechanism(s) control the movement of gas, two independent experimental studies on Callovo-Oxfordian claystone (COx) have been undertaken at the British Geological Survey (BGS) and LAEGO–ENSG Nancy (LAEGO).

The study conducted at BGS used a triaxial apparatus specifically designed to resolve very small volumetric (axial and radial) strains potentially associated with the onset of gas flow. The LAEGO study utilized a triaxial setup with axial and radial strains measured by strain gauges glued to the sample. Both studies were conducted on COx at
in situ
stresses representative of the Bure Underground Research Laboratory (URL), with flux and pressure of gas and water carefully monitored throughout long-duration experiments.

A four-stage model has been postulated to explain the experimental results. Stage 1: gas enters at the gas entry pressure. Gas propagation is along dilatant pathways that exploit the pore network of the material. Around each pathway the fabric compresses, which may lead to localized movement of water away from the pathways. Stage 2: the dendritic flow path network has reached the mid-plane of the sample, resulting in acceleration of the observed radial strain. During this stage, outflow from the sample also develops. Stage 3: gas has reached the backpressure end of the sample with end-to-end movement of gas. Dilation continues, indicating that gas pathway numbers have increased. Stage 4: gas-fracturing occurs with a significant tensile fracture forming, resulting in failure of the sample.

Both studies clearly showed that as gas started to move through the COx, the sample underwent mechanical dilation (i.e. an increase in sample volume). Under
in situ
conditions, the onset of dilation (micro-fissuring) is a necessary precursor for the advective movement of gas.
Numerical modelling of moisture controlled laboratory swelling/shrinkage experiments on argillaceous rocks
Authors: Xu W. J. , Shao H. , Hesser J. , Kolditz O. 
Published: May 2014

Abstract
Moisture-induced swelling and shrinkage deformation is a well-known phenomenon for clayey material. To quantify this deformation a fully coupled thermal-hydro-mechanical (TH2M) model based on the modified effective stress concept has been developed and implemented in the numerical code OGS. Three laboratory tests have been analysed using this concept. All specimens for the tests are argillaceous rocks, from different underground laboratory sites (Tournemire, Bure, France, and Mont Terri, Switzerland). The laboratory tests are performed under different conditions; the first test is free swelling/shrinkage and other two tests are with uniaxial loading. The relative humidity is also controlled. Only one test is carried out under varied temperature conditions. In this study the anisotropic swelling/shrinkage deformation wais simulated and analysed using this modified effective stress concept.
Re-engineering Vesicular Stomatitis Virus to Abrogate Neurotoxicity, Circumvent Humoral Immunity, and Enhance Oncolytic Potency
Authors: Muik Alexander , Stubbert Lawton J. , Jahedi Roza Z. , Geiβ Yvonne , Kimpel Janine , Dold Catherine , Tober Reinhard , Volk Andreas , Klein Sabine , Dietrich Ursula , Yadollahi Beta , Falls Theresa , Miletic Hrvoje , Stojdl David , Bell John C. , von Laer Dorothee 
Published: May 2014

AbstractAs cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP), creating a replicating therapeutic, rVSV(GP), that is benign in normal brain but can effectively eliminate brain cancer in multiple preclinical tumor models in vivo. Furthermore, it can be safely administered systemically to mice and displays greater potency against a spectrum of human cancer cell lines than current OV candidates. Remarkably, rVSV(GP) escapes humoral immunity, thus, for the first time, allowing repeated systemic OV application without loss of therapeutic efficacy. Taken together, rVSV(GP) offers a considerably improved OV platform that lacks several of the major drawbacks that have limited the clinical potential of this technology to date. Cancer Res; 74(13); 3567–78. ©2014 AACR.
Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin, and Other Platinum Complexes
Authors: Hall Matthew D. , Telma Katherine A. , Chang Ki-Eun , Lee Tobie D. , Madigan James P. , Lloyd John R. , Goldlust Ian S. , Hoeschele James D. , Gottesman Michael M. 
Published: May 2014

AbstractThe platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence are extensively studied in the laboratory setting. In this study, we examined the literature and found a significant number of studies (11%–34%) in prominent cancer journals utilizing cisplatin dissolved in DMSO. However, dissolving cisplatin in DMSO for laboratory-based studies results in ligand displacement and changes to the structure of the complex. We examined the effect of DMSO on platinum complexes, including cisplatin, carboplatin, and oxaliplatin, finding that DMSO reacted with the complexes, inhibited their cytotoxicity and their ability to initiate cell death. These results render a substantial portion of the literature on cisplatin uninterpretable. Raising awareness of this significant issue in the cancer biology community is critical, and we make recommendations on appropriate solvation of platinum drugs for research. Cancer Res; 74(14); 3913–22. ©2014 AACR.
The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer
Authors: Hjelmborg Jacob B. , Scheike Thomas , Holst Klaus , Skytthe Axel , Penney Kathryn L. , Graff Rebecca E. , Pukkala Eero , Christensen Kaare , Adami Hans-Olov , Holm Niels V. , Nuttall Elizabeth , Hansen Steinbjorn , Hartman Mikael , Czene Kamila , Harris Jennifer R. , Kaprio Jaakko , Mucci Lorelei A. 
Published: May 2014

Abstract
Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.
Methods: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.
Results: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability [heritability = 58% (95% confidence interval, 52%–63%)] of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary.
Conclusions: Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age.
Impact: Findings affect the search for genetic and epigenetic markers and frame prevention efforts. Cancer Epidemiol Biomarkers Prev; 23(11); 2303–10. ©2014 AACR.
Prescription Diuretic Use and Risk of Basal Cell Carcinoma in the Nationwide U.S. Radiologic Technologists Cohort
Authors: McDonald Emily , Freedman D. Michal , Alexander Bruce H. , Doody Michele M. , Tucker Margaret A. , Linet Martha S. , Cahoon Elizabeth K. 
Published: May 2014

Abstract
Background: UV radiation (UVR) exposure is the primary risk factor for basal cell carcinoma (BCC). Although prescription diuretics have photosensitizing properties, the relationship between diuretic use and BCC remains unclear.
Methods: Using data from the United States Radiologic Technologists Study, a large, nationwide prospective cohort, we assessed the relationship between diuretic use and first primary BCC while accounting for sun exposure history, constitutional characteristics, lifestyle factors, and anthropometric measurements for geographically dispersed individuals exposed to a wide range of ambient UVR.
Results: After adjustment for potential confounders, we found a significantly increased risk of BCC associated with diuretic use [HR, 1.22; 95% confidence interval (CI), 1.07–1.38]. This relationship was modified by body mass index (P = 0.019), such that BCC risk was increased with diuretic use in overweight (HR, 1.43; 95% CI, 1.16–1.76) and obese individuals (HR, 1.43; 95% CI, 1.09–1.88), but not in normal weight individuals (HR, 0.99; 95% CI, 0.81–1.21).
Conclusions: Increased risk of BCC associated with diuretic use in overweight and obese participants may be related to higher dosages, longer duration of medication use, reduced drug metabolism, or drug interactions.
Impact: Future cohort studies should obtain more detailed information on medication use, consider factors that affect drug metabolism, and measure intermediate endpoints such as photosensitivity reactions. Cancer Epidemiol Biomarkers Prev; 23(8); 1539–45. ©2014 AACR.
Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-EGFR Antibodies Converge on MEK/ERK Pathway Activation and Can Be Overcome by Combined MEK/EGFR Inhibition
Authors: Troiani Teresa , Napolitano Stefania , Vitagliano Donata , Morgillo Floriana , Capasso Anna , Sforza Vincenzo , Nappi Anna , Ciardiello Davide , Ciardiello Fortunato , Martinelli Erika 
Published: May 2014

Abstract
Purpose: The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab.
Experimental Design: We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab.
Results: Among the colorectal cancer cell lines, five with a KRAS mutation (LOVO, HCT116, HCT15, SW620, and SW480) and one with a BRAF mutation (HT29) were resistant to the antiproliferative effects of cetuximab, whereas two cells (GEO and SW48) were highly sensitive. Treatment with BAY 86-9766 determined dose-dependent growth inhibition in all cancer cells, including two human colorectal cancer cells with acquired resistance to cetuximab (GEO-CR and SW48-CR), with the exception of HCT15 cells. Combined treatment with cetuximab and BAY 86-9766 induced a synergistic antiproliferative and apoptotic effects with blockade in the MAPK and AKT pathway in cells with either primary or acquired resistance to cetuximab. The synergistic antiproliferative effects were confirmed using other two selective MEK1/2 inhibitors, selumetinib and pimasertib, in combination with cetuximab. Moreover, inhibition of MEK expression by siRNA restored cetuximab sensitivity in resistant cells. In nude mice bearing established human HCT15, HCT116, SW48-CR, and GEO-CR xenografts, the combined treatment with cetuximab and BAY 86-9766 caused significant tumor growth inhibition and increased mice survival.
Conclusion: These results suggest that activation of MEK is involved in both primary and acquired resistance to cetuximab and the inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance in patients with colorectal cancer. Clin Cancer Res; 20(14); 3775–86. ©2014 AACR.
MET as a Target in Papillary Renal Cell Carcinoma
Authors: Fay André P. , Signoretti Sabina , Choueiri Toni K. 
Published: May 2014

Abstract
The biology underlying papillary renal cell carcinoma (pRCC) is largely unknown, and no specific therapies have been developed for advanced disease. The elucidation of the MET pathway status in types I and II pRCC may help to select patients who are more likely to benefit from MET inhibitors. Clin Cancer Res; 20(13); 3361–3. ©2014 AACR.
Prevention of Abdominal Aortic Aneurysm by Anti–MicroRNA-712 or Anti–MicroRNA-205 in Angiotensin II–Infused Mice
Authors: Kim Chan Woo , Kumar Sandeep , Son Dong Ju , Jang In-Hwan , Griendling Kathy K. , Jo Hanjoong 
Published: May 2014

Objective—
Abdominal aortic aneurysm (AAA) is characterized as a progressive dilation and degradation of the aortic wall, associated with activation of matrix metalloproteinases (MMPs) and inflammation. Emerging evidence indicates a role for microRNAs (miRNAs) in AAA pathogenesis, but it is unclear whether abdominal aortic endothelial miRNAs play a role in the disease process. We aimed to identify miRNAs in the abdominal aortic endothelium that play a critical role in AAA development.

Approach and Results—

The mouse model of AAA induced by angiotensin II infusion was used in this study. Through a miRNA array and validation study, we initially identified the murine-specific miR-712 and subsequently its human/murine homolog miR-205 as angiotensin II–induced miRNAs in the abdominal aortic endothelium in vivo and in vitro. Mechanistically, miR-712 stimulated MMP activity in the aortic wall by directly targeting 2 MMP inhibitors: tissue inhibitor of metalloproteinase 3 (TIMP3) and reversion-inducing cysteine-rich protein with kazal motifs (RECK). Silencing of miR-712 and miR-205 by using anti–miR-712 and anti–miR-205, respectively, significantly decreased the aortic MMP activity and inflammation, preventing AAA development in angiotensin II–infused ApoE
−/−
mice. Further, upregulation of 4 angiotensin II–sensitive miRNAs, miR-205, -21, -133b, and -378, identified in this murine study were confirmed in human AAA samples compared with nondiseased control.

Conclusions—

Our results demonstrate that angiotensin II–sensitive miR-712 and its human homolog miR-205 downregulate
TIMP3
and
RECK
, which in turn stimulate aortic MMP activity and inflammation, leading to AAA development. Targeting these miRNAs may be a novel therapeutic strategy to prevent AAA.
Redox Regulation of 14-3-3ζ Controls Monocyte Migration
Authors: Kim Hong Seok , Ullevig Sarah L. , Nguyen Huynh Nga , Vanegas Difernando , Asmis Reto 
Published: May 2014

Objective—
Metabolic stress primes monocytes for accelerated chemokine-mediated adhesion, migration, and recruitment into vascular lesions by increasing actin remodeling. The mechanism linking metabolic stress to accelerated actin turnover and enhanced monocyte migration was not known. We tested the hypothesis that in metabolically primed monocytes, the acceleration of monocyte chemoattractant protein-1–induced chemotaxis is mediated by the hyperactivation of cofilin.

Approach and Results—

Metabolic priming was induced by exposing human THP-1 monocytes to diabetic conditions, that is, human native low-density lipoprotein plus high glucose concentrations. In healthy monocytes, monocyte chemoattractant protein-1 induced the phosphorylation and inactivation of cofilin. This response was completely blocked in metabolically primed monocytes but restored by overexpression of the thiol transferase, glutaredoxin 1. Cofilin kinase, LIM kinase 1, and cofilin phosphatase, Slingshot-1L, were not affected by metabolic stress. However, metabolic priming increased 3.8-fold the
S
-glutathionylation of the Slingshot-1L-binding protein 14-3-3ζ (zeta), resulting in its caspase-dependent degradation. Glutaredoxin 1 overexpression inhibited low-density lipoprotein plus high glucose–induced
S
-glutathionylation and degradation of 14-3-3ζ. The C25S mutant of 14-3-3ζ was resistant to both
S
-glutathionylation and degradation induced by low-density lipoprotein plus high glucose. Overexpression of the C25S mutant restored monocyte chemoattractant protein-1–induced cofilin phosphorylation and prevented accelerated migration of metabolically stressed monocytes, suggesting that loss of 14-3-3ζ increases the pool of free Slingshot-1L phosphatase, thereby preventing the phosphorylation and deactivation of cofilin in response to chemokine activation.

Conclusions—
By preventing the inactivation of cofilin, metabolic stress–induced degradation of 14-3-3ζ promotes the conversion of blood monocytes into a hypermigratory, proatherogenic phenotype.