bluuebunny/crossref_metadata_2025_split huggingface dataset:
RECIST: No Longer the Sharpest Tool in the Oncology Clinical Trials Toolbox—Point
Authors: Sharma Manish R. , Maitland Michael L. , Ratain Mark J. 
Published: September 2012

Abstract
Although “response” has been an attractive term for oncologists and patients, oncologists really want to know which therapy to start for a given patient and when to discontinue that therapy in favor of an alternative. In efficacy trials, cancer therapeutics have conventionally been assessed by endpoints that are based on the categorical Response Evaluation Criteria In Solid Tumors (RECIST) system. In this article, we make the case for a new paradigm in which therapeutics are assessed on a continuous scale by evidence of efficacy, using a variety of quantitative tools that take advantage of technologic innovations and increasing understanding of cancer biology. The new paradigm relies on randomized comparisons between investigational arms and control arms, as historical controls are unavailable or unreliable for these quantitative measures. We discuss multiple limitations of RECIST, including its overemphasis on tumor regression, concerns about the accuracy of tumor measurements and the validity of comparisons with historical controls, and its inadequacy in disease settings in which tumor measurements on cross-sectional imaging are difficult or uninformative. We discuss how the new paradigm overcomes these limitations and provides a framework for answering the key questions of the oncologist and improving patient outcomes. Cancer Res; 72(20); 5145–9. ©2012 AACR.
SINE Retrotransposons Cause Epigenetic Reprogramming of Adjacent Gene Promoters
Authors: Estécio Marcos R.H. , Gallegos Juan , Dekmezian Mhair , Lu Yue , Liang Shoudan , Issa Jean-Pierre J. 
Published: September 2012

Abstract
Almost half of the human genome and as much as 40% of the mouse genome is composed of repetitive DNA sequences. The majority of these repeats are retrotransposons of the SINE and LINE families, and such repeats are generally repressed by epigenetic mechanisms. It has been proposed that these elements can act as methylation centers from which DNA methylation spreads into gene promoters in cancer. Contradictory to a methylation center function, we have found that retrotransposons are enriched near promoter CpG islands that stay methylation-free in cancer. Clearly, it is important to determine which influence, if any, these repetitive elements have on nearby gene promoters. Using an in vitro system, we confirm here that SINE B1 elements can influence the activity of downstream gene promoters, with acquisition of DNA methylation and loss of activating histone marks, thus resulting in a repressed state. SINE sequences themselves did not immediately acquire DNA methylation but were marked by H3K9me2 and H3K27me3. Moreover, our bisulfite sequencing data did not support that gain of DNA methylation in gene promoters occurred by methylation spreading from SINE B1 repeats. Genome-wide analysis of SINE repeats distribution showed that their enrichment is directly correlated with the presence of USF1, USF2, and CTCF binding, proteins with insulator function. In summary, our work supports the concept that SINE repeats interfere negatively with gene expression and that their presence near gene promoters is counter-selected, except when the promoter is protected by an insulator element. Mol Cancer Res; 10(10); 1332–42. ©2012 AACR.
The Great Escape: Microbiotal LPS Takes a Toll on the Liver
Authors: Weiss David S. 
Published: September 2012

Abstract
The interaction between the intestinal microbiota and host is much more complex than previously appreciated, and we are now learning that it can have an impact on extraintestinal human diseases. In this issue of the journal (beginning on page 1090), Lin and colleagues present important data linking the microbiota, lipopolysaccharide (LPS), and toll-like receptor (TLR)4 with hepatitis in a mouse model. These provocative results and those from other recent studies highlight the microbiota as a potential target for therapeutic intervention in several liver diseases. Cancer Prev Res; 5(9); 1078–80. ©2012 AACR.
The Short-Term Effects of Vitamin D Repletion on Cholesterol
Authors: Ponda Manish P. , Dowd Kathleen , Finkielstein Dennis , Holt Peter R. , Breslow Jan L. 
Published: September 2012

Objective—
Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile.

Methods and Results—

One hundred fifty-one vitamin D−deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other n
uclear magnetic resonance
−based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [−80 to +116 nmol/L];
P
=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [−1.4 to +13.0 mg/dL],
P
=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [−2.5 to +10.2 mg/dL],
P
=0.13); high–density lipoprotein cholesterol (+0.4 mg/dL 95% CI [−1.6 to +2.6 mg/dL],
P
=0.71); and triglycerides (+7.9 mg/dL 95% CI [−6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (
P
<0.001) and inversely with the changes in serum parathyroid hormone (
P
=0.02).

Conclusion—
In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01008384.
Different Impacts of Blood Pressure Variability on the Progression of Cerebral Microbleeds and White Matter Lesions
Authors: Liu Wenhong , Liu Ran , Sun Wei , Peng Qing , Zhang Weiwei , Xu En , Cheng Yan , Ding Meiping , Li Yansheng , Hong Zhen , Wu Jiang , Zeng Jinsheng , Yao Chen , Huang Yining ,   for the CASISP Study Group
Published: September 2012

Background and Purpose—
Cerebral microbleeds (CMB) and white matter lesions (WML) are cerebral small vessel diseases. Hypertension is considered the most important risk factor. Its mechanism is not yet clarified. Our study assessed the association of blood pressure variability (BPV) with CMB and WML progression.

Methods—
Patients with a history of ischemic stroke within 1 to 6 months were consecutively recruited and followed-up for 12 to 18 months. Blood pressure was measured monthly and controlled to a target level. BPV was quantified by the maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of mean, and successive variation independent of mean. Magnetic resonance imaging was performed at baseline and the end of the study. CMB and WML were rated using Microbleed Anatomic Rating Scale and Age-Related White Matter Changes scales, respectively. Multiple logistic analyses assessed BPV associations with CMB and WML development.

Results—

Of 720 patients recruited, 500 and 584 had follow-up results for CMB and WML, respectively; 13.2% and 48.1% showed CMB and WML progression, respectively, over a median of 14 months. Patients with CMB had a higher mean, maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of the mean, and successive variation independent of the mean in either systolic blood pressure or diastolic blood pressure (
P
<0.05). Systolic blood pressure variability was an independent risk factor for deep and infratentorial CMB progression, whereas diastolic blood pressure variability was independently associated with CMB development in deep regions. WML progression was not significantly associated with BPV between visits.

Conclusion—
BPV independently predicts CMB progression in deep and infratentorial regions.

Clinical Trial Registration Information—

URL:
http://www.clinicaltrials.gov
. Unique identi-fier: NCT00202020.
Silent Stroke
Authors: Saini Monica , Ikram Kamran , Hilal Saima , Qiu Anqi , Venketasubramanian Narayanaswamy , Chen Christopher 
Published: September 2012

Background and Purpose—
The prevalence of silent brain infarcts varies from 8% to 28% in the general elderly population. Silent brain infarcts are associated with increased risk of subsequent stroke and cognitive dysfunction. By definition, silent strokes lack clinically overt stroke-like symptoms and fail to come to clinical attention; however, impaired recall of symptoms may be a potential confounder. Our aim is to report a series of patients with incidentally detected acute and subacute strokes and examine whether they were truly asymptomatic.

Methods—
Subjects included in this study were drawn from ongoing dementia research studies at the Memory Ageing and Cognition Center, in which all participants underwent a cranial MRI. Incidental hyperintense lesions on diffusion-weighted imaging with corresponding apparent diffusion coefficient defects indicative of acute/subacute silent stroke were identified. Clinical data for individuals with incidental hyperintense lesions on diffusion-weighted imaging were collated.

Results—
Six of 649 subjects had incidental hyperintense lesions on diffusion-weighted imaging; on retrospective questioning, 3 recalled symptoms temporally correlated with MRI lesions, which had been reported to but ignored by family members. Two subjects had focal neurological signs. A majority of the subjects with incidental hyperintense lesions on diffusion-weighted imaging had significant cognitive impairment.

Conclusions—
A significant number of strokes may be “silent” due to lack of awareness of stroke-like symptoms in the elderly and their families. Enhanced stroke prevention education strategies are needed for the elderly population and, in particular, for their families.
High-Resolution Modeling of Typhoon Morakot (2009): Vortex Rossby Waves and Their Role in Extreme Precipitation over Taiwan
Authors: Hall Jonathan D. , Xue Ming , Ran Lingkun , Leslie Lance M. 
Published: September 2012

AbstractA high-resolution nonhydrostatic numerical model, the Advanced Regional Prediction System (ARPS), was used to simulate Typhoon Morakot (2009) as it made landfall over Taiwan, producing record rainfall totals. In particular, the mesoscale structure of the typhoon was investigated, emphasizing its associated deep convection, the development of inner rainbands near the center, and the resultant intense rainfall over western Taiwan.Simulations at 15- and 3-km grid spacing revealed that, following the decay of the initial inner eyewall, a new, much larger eyewall developed as the typhoon made landfall over Taiwan. Relatively large-amplitude wave structures developed in the outer eyewall and are identified as vortex Rossby waves (VRWs), based on the wave characteristics and their similarity to VRWs identified in previous studies.Moderate to strong vertical shear over the typhoon system produced a persistent wavenumber-1 (WN1) asymmetric structure during the landfall period, with upward motion and deep convection in the downshear and downshear-left sides, consistent with earlier studies. This strong asymmetry masks the effects of WN1 VRWs. WN2 and WN3 VRWs apparently are associated with the development of deep convective bands in Morakot’s southwestern quadrant. This occurs as the waves move cyclonically into the downshear side of the cyclone. Although the typhoon track and topographic enhancement contribute most to the record-breaking rainfall totals, the location of the convective bands, and their interaction with the mountainous terrain of Taiwan, also affect the rainfall distribution. Quantitatively, the 3-km ARPS rainfall forecasts are superior to those obtained from coarser-resolution models.
Nav1.5 sodium channels in macrophages in multiple sclerosis lesions
Authors: Black Joel A , Newcombe Jia , Waxman Stephen G 
Published: September 2012

Background: Macrophages are dynamic participants in destruction of white matter in active multiple sclerosis (MS) plaques. Regulation of phagocytosis and myelin degradation along endosomal pathways in macrophages is highly-orchestrated and critically-dependent upon acidification of endosomal lumena. Evidence from in vitro studies with macrophages and THP-1 cells suggests that sodium channel Nav1.5 is present in the limiting membrane of maturing endosomes where it plays a prominent role in the accumulation of protons. However, a contribution of the Nav1.5 channel to macrophage-mediated events in vivo has not been demonstrated. Method: We examined macrophages within active MS lesions by immunohistochemistry to determine whether Nav1.5 is expressed in these cells in situ and, if expressed, whether it is localized to specific compartments along the endocytic pathway. Results: Our results demonstrate that Nav1.5 is expressed within macrophages in active MS lesions, and that it is preferentially expressed in late endosomes and phagolysosomes (Rab7+, LAMP-1+), and sparsely expressed in early (EEA-1+) endosomes. Triple-immunolabeling studies showed localization of Nav1.5 within Rab7+ endosomes containing proteolipid protein, a myelin marker, in macrophages within active MS plaques. Conclusions: These observations support the suggestion that Nav1.5 contributes to the phagocytic pathway of myelin degradation in macrophages in vivo within MS lesions.
Iron oxide catalysts: Fenton and Fentonlike reactions – a review
Authors: Pereira M. C. , Oliveira L. C. A. , Murad E. 
Published: September 2012

AbstractIron is the fourth most common element by mass in the Earth's crust and forms compounds in several oxidation states. Iron (hydr)oxides, some of which form inherently and exclusively in the nanometre-size range, are ubiquitous in nature and readily synthesized. These facts add up to render many Fe (hydr)oxides suitable as catalysts, and it is hardly surprising that numerous studies on the applications of Fe (hydr)oxides in catalysis have been published. Moreover, the abundant availability of a natural Fe source from rocks and soils at minimal cost makes the potential use of these as heterogeneous catalyst attractive.Besides those Fe (hydr)oxides that are inherently nanocrystalline (ferrihydrite, Fe5HO8.4H2O, and feroxyhyte, δ’-FeOOH), magnetite (Fe3O4) is often used as a catalyst because it has a permanent magnetization and contains Fe in both the divalent and trivalent states. Hematite, goethite and lepidocrocite have also been used as catalysts in their pure forms, doped with other cations, and as composites with carbon, alumina and zeolites among others.In this review we report on the use of synthetic and natural Fe (hydr)oxides as catalysts in environmental remediation procedures using an advanced oxidation process, more specifically the Fenton-like system, which is highly efficient in generating reactive species such as hydroxyl radicals, even at room temperature and under atmospheric pressure. The catalytic efficiency of Fe (hydr)oxides is strongly affected by factors such as the Fe oxidation state, surface area, isomorphic substitution of Fe by other cations, pH and temperature.
Microtexture and genesis of clay minerals from a turbiditic sequence in a Southern Pyrenees foreland basin (Jaca basin, Eocene)
Authors: Bauluz B. , Yuste A. , Mayayo M. J. , Rodríguez-Navarro A. B. , González-López J. M. 
Published: September 2012

AbstractA set of fine-grained samples from a turbiditic sequence in a Southern Pyrenees foreland basin (Jaca Basin, Eocene) were studied to determine the influence of tectonics (Pyrenean Orogeny) on phyllosilicate recrystallization and infer the grade and basin maturity. The samples from four different outcrops were examined by X-ray diffraction (XRD) and by scanning (SEM) and transmission electron microscopy (TEM) with special emphasis on clay-mineral characterization (e.g.illitic phases). The analysed samples have simple mineral assemblages and consist of detrital quartz, albite and calcite, scarce clay matrix (mainly illite with chlorite), and calcite and dolomite cement. The lack of other phyllosilicates such as mixed-layer illite-smectite (I-S), pyrophyllite, Na-micas, or kaolin minerals is quite remarkable. On the SEM scale, samples (with marl composition) have poorly sorted textures and high detrital contents. In many cases they show bedding and/or cleavage, and in some cases neither is observed. Most of the clay-sized illites show very similar crystallinity and b0 values (determined by XRD) and distributions of crystallite thickness (measured by TEM) in all the outcrops, which is typical of late-diagenesis illites forming under low-pressure conditions. These illites are parallel (or subparallel) to bedding or randomly orientated. They are also characterized by disordered polytypes and low K contents. In some TEM images, a second type of illite has been observed. This secondary illite occurs parallel to cleavage, with thicker crystals (25–35 layers), K contents in the interlayer, and a 2M1 polytype. The pole figure analysis shows that most of the clays have (00l) planes parallel (or subparallel) to bedding although there are abundant clays with random orientation. There is no trend in the clay orientation/disorientation from the south to the north of the basin. All the data indicate that the strain rate associated with the Pyrenean Orogeny has not been recorded in the turbidite sequence controlling the relative orientation of clays, although anchizonal clay crystallization is favoured as a minor process.
Halloysite in Argentinian deposits: origin and textural constraints
Authors: Cravero F. , Maiza P. J. , Marfil S. A. 
Published: September 2012

AbstractIn Argentina, the only halloysite deposits found so far are located in the southwest of the province of Rio Negro. The areas are named Mamil Choique and Buitrera, separated by 50 km in a W–E direction. The deposits are located in pyroclastic rocks, rhyolitic tuffs and ignimbrites.The aim of this paper is to determine the origin of the alteration, any relationship between the processes in Mamil Choique and Buitrera, and the factors which controlled the halloysite formation. The work was based on field work, mineralogical and geochemical studies, form and distribution of the alteration. Fresh as well as altered rocks were collected. The first were studied by petrographic and chemical methods. In altered samples, the clay mineralogy was determined by XRD and textures by SEM and TEM. Chemical analyses on fresh and altered samples were used to characterize the alteration process and the rock composition.It was concluded that halloysite has been formed by weathering in a time range from Middle Eocene to Middle Oligocene and extended along 50 km in a W-E direction, independent of the source rock. Particle morphology depends on the original texture of the rock. Spheroidal halloysite is related to rocks with low porosity and tubular particles are related to rocks with open spaces.
A simple approach for producing high aspect ratio fluorohectorite nanoplatelets utilizing a stirred media mill (ball mill)
Authors: Ziadeh M. , Chwalka B. , Kalo H. , Schütz M. R. , Breu J. 
Published: September 2012

AbstractThe potential of platy nanofillers like clays in polymer nanocomposites is mostly determined by their aspect ratio. The degree of improvement that may be achieved in respect to reinforcement, gas-barrier properties and flame retardancy critically depends on the aspect ratio. Thus, increasing the aspect ratio is highly desirable in order to explore the full potential of the clay filler. Mechanical shear stress as generated in the grinding chamber of a stirred media mill (ball mill) induced an efficient exfoliation of highly hydrated and therefore ‘shear-labile’ synthetic Mg-fluorohectorite in aqueous dispersion. The attainable degree of exfoliation can be tuned and controlled through the shear forces applied by changing process parameters such as solid content and grinding media diameter. Characterization and evaluation of the exfoliation efficiency during milling was achieved by combining and cross-validating data obtained by powder X-ray diffraction (XRD), static light scattering (SLS), specific surface area measurements applying the Brunauer-Emmett-Teller (BET) equation, and scanning electron microscopy (SEM). This led to the identification of optimal processing parameters, allowing for control of the degree of exfoliation and, consequently, the aspect ratio of the nanoplatelets. Not surprisingly, besides exfoliation, increasing the magnitude of the shear stress also resulted in some reduction in platelet size.The clay platelets obtained showed a high average aspect ratio (>600), several times greater than that of original synthetic fluorohectorite. The increase of aspect ratio was reflected in a significant enhancement of both specific surface area and cation exchange capacity (CEC) of the external basal surfaces. This method has substantial advantages compared to microfluidizer processing with respect to feasibility, batch size and particle diameter size preservation. The exfoliated nanoplatelets obtained by milling have great potential to improve mechanical properties of polymer layered silicate nanocomposites (PLSN).
Effect of heating vermiculites on extractability of phosphorus and some essential plant micronutrients
Authors: Marwa E. M. M. , Meharg A. A. , Rice C. M. 
Published: September 2012

AbstractThe study assessed the effect of heating vermiculites on extractability of phosphorus, iron, zinc and manganese with respect to their potential agricultural use. Of these elements, phosphorus was from apatite and monazite that occur as accessory minerals in vermiculites. Vermiculites were heated at 15–800°C and digested by acetic acid for extracting phosphorus and diethylene triamine pentaacetic acid (DTPA) for extracting zinc, iron and manganese. Phosphorus in the extract was analysed by a flow injection method while zinc, iron and manganese were measured by atomic absorption spectrometry. The results showed that heating vermiculites to 400°C enhanced extractability of phosphorus from apatite and monazite to a level of 335 mg kg–1. Further heating to 800°C reduced extractable phosphorus to less than 75 mg kg–1. Maximum extractable zinc, iron and manganese found were 2.7, 19.1 and 22.9 mg kg–1, respectively, values that are beneficial and tolerable by most plants. Thus, it was concluded that heating vermiculites to ⩽ 400°C optimizes extractability of phosphorus from incorporated apatite and monazite and some essential plant micronutrients in vermiculites.