bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance of Glioblastoma-Initiating Cells to Radiation Mediated by the Tumor Microenvironment Can Be Abolished by Inhibiting Transforming Growth Factor-β
Authors: Hardee Matthew E. , Marciscano Ariel E. , Medina-Ramirez Christina M. , Zagzag David , Narayana Ashwatha , Lonning Scott M. , Barcellos-Hoff Mary Helen 
Published: June 2012

Abstract
The poor prognosis of glioblastoma (GBM) routinely treated with ionizing radiation (IR) has been attributed to the relative radioresistance of glioma-initiating cells (GIC). Other studies indicate that although GIC are sensitive, the response is mediated by undefined factors in the microenvironment. GBM produce abundant transforming growth factor-β (TGF-β), a pleotropic cytokine that promotes effective DNA damage response. Consistent with this, radiation sensitivity, as measured by clonogenic assay of cultured murine (GL261) and human (U251, U87MG) glioma cell lines, increased by approximately 25% when treated with LY364947, a small-molecule inhibitor of TGF-β type I receptor kinase, before irradiation. Mice bearing GL261 flank tumors treated with 1D11, a pan-isoform TGF-β neutralizing antibody, exhibited significantly increased tumor growth delay following IR. GL261 neurosphere cultures were used to evaluate GIC. LY364947 had no effect on the primary or secondary neurosphere-forming capacity. IR decreased primary neurosphere formation by 28%, but did not reduce secondary neurosphere formation. In contrast, LY364947 treatment before IR decreased primary neurosphere formation by 75% and secondary neurosphere formation by 68%. Notably, GL261 neurospheres produced 3.7-fold more TGF-β per cell compared with conventional culture, suggesting that TGF-β production by GIC promotes effective DNA damage response and self-renewal, which creates microenvironment-mediated resistance. Consistent with this, LY364947 treatment in irradiated GL261 neurosphere-derived cells decreased DNA damage responses, H2AX and p53 phosphorylation, and induction of self-renewal signals, Notch1 and CXCR4. These data motivate the use of TGF-β inhibitors with radiation to improve therapeutic response in patients with GBM. Cancer Res; 72(16); 4119–29. ©2012 AACR.
Functional Interaction of Tumor Suppressor DLC1 and Caveolin-1 in Cancer Cells
Authors: Du Xiaoli , Qian Xiaolan , Papageorge Alex , Schetter Aaron J. , Vass William C. , Liu Xi , Braverman Richard , Robles Ana I. , Lowy Douglas R. 
Published: June 2012

Abstract
Deleted in liver cancer 1 (DLC1), a tumor suppressor gene frequently inactivated in non–small cell lung cancer (NSCLC) and other malignancies, encodes a multidomain protein with a RhoGTPase-activating (RhoGAP) domain and a StAR-related lipid transfer (START) domain. However, no interacting macromolecule has been mapped to the DLC1 START domain. Caveolin-1 (CAV-1) functions as a tumor suppressor in most contexts and forms a complex with DLC1. Here, we have mapped the region of DLC1 required for interaction with CAV-1 to the DLC1 START domain. Mutation of the DLC1 START domain disrupted the interaction and colocalization with CAV-1. Moreover, DLC1 with a START domain mutation failed to suppress neoplastic growth, although it negatively regulated active Rho. CAV-1 and DLC1 expression levels were correlated in two public datasets of NSCLC lines and in two independent publicly available mRNA expression datasets of NSCLC tumors. Clinically, low DLC1 expression predicted a poor clinical outcome in patients with lung cancer. Together, our findings indicate that complex formation between the DLC1 START domain and CAV-1 contributes to DLC1 tumor suppression via a RhoGAP-independent mechanism, and suggest that DLC1 inactivation probably contributes to cancer progression. Cancer Res; 72(17); 4405–16. ©2012 AACR.
Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma
Authors: Lee Sun Joo , Ghosh Sukhen C. , Han Hee Dong , Stone Rebecca L. , Bottsford-Miller Justin , Shen De Yue , Auzenne Edmond J. , Lopez-Araujo Alejandro , Lu Chunhua , Nishimura Masato , Pecot Chad V. , Zand Behrouz , Thanapprapasr Duangmani , Jennings Nicholas B , Kang Yu , Huang Jie , Hu Wei , Klostergaard Jim , Sood Anil K. 
Published: June 2012

Abstract
Purpose: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown to result in reduced normal tissue toxicity and to minimize “off-treatment” exposure resulting in an improved therapeutic ratio.
Experimental Design: We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1 or HeyA8 ovarian cancer cells were treated intraperitoneally (i.p.) with MET HA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects.
Results: All MET HA-TXL–treated mice and the MTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values &lt; 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL–treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistant HeyA8-MDR model, significant reduction in tumor weight and nodule counts was noted in the metronomic groups whereas the response of the MTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis.
Conclusions: This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism. Clin Cancer Res; 18(15); 4114–21. ©2012 AACR.
A Pragmatic Approach Using Magnetic Resonance Imaging to Treat Ischemic Strokes of Unknown Onset Time in a Thrombolytic Trial
Authors: Song Shlee S. , Latour Lawrence L. , Ritter Carsten H. , Wu Ona , Tighiouart Mourad , Hernandez Daymara A. , Ku Katherine D. , Luby Marie , Warach Steven 
Published: June 2012

Background and Purpose—
Toward the goal of designing a clinical trial using imaging parameters to treat stroke patients with unknown onset time, we investigated the timing of changes on MRI in patients with well-defined stroke onset.

Methods—
Hypothesis-generating (n=85) and confirmatory (n=111) samples were scored by blinded readers for fluid-attenuated inversion recovery (FLAIR) hyperintensity in diffusion-positive regions. Reader-measured signal intensity ratio (SIR) of the lesion to contralateral tissue was compared with SIR measured by coregistration.

Results—

Lesion conspicuity increased with time on FLAIR (
P
=0.006). Qualitative assessment of FLAIR-negative vs FLAIR hyperintensity (k=0.7091; 95% CI, 0.61–0.81) showed good interrater agreement. Subtle hyperintensity was less reliably categorized (k=0.59; 95% CI, 0.47–0.71). Reader-measured SIR <1.15 can identify patients within the treatable time window of 4.5 hours (positive predictive value=0.90). The SIR was greater for right hemisphere lesions (
P
=0.04) for a given reported time from stroke symptom onset.

Conclusion—
The SIR on FLAIR provides a quantitative tool to identify early ischemic strokes. In developing SIR thresholds, right hemisphere lesions may confound the accurate estimate of stroke onset time. Image coregistration for thrombolytic trial enrollment is not necessary. A SIR <1.15 on FLAIR yields a practical estimate of stroke onset within 4.5 hours.
Moyamoya Disease-Related Versus Primary Intracerebral Hemorrhage
Authors: Nah Hyun-Wook , Kwon Sun U. , Kang Dong-Wha , Ahn Jae-Sung , Kwun Byung-Duk , Kim Jong S. 
Published: June 2012

Background and Purpose—
The purpose of our study was to compare lesion location between moyamoya disease-related intracerebral hemorrhage (MMD-ICH) and primary intracerebral hemorrhage (P-ICH).

Methods—
Ninety-three patients each with MMD-ICH and P-ICH were compared. In patients with MMD-ICH, angiographic findings were assessed with special attention to the prominent anterior choroidal artery. Follow-up data were obtained through clinical visit and telephone interview.

Results—

The location of hemorrhage was different between MMD-ICH and P-ICH, the most frequent one being intraventricular region (37.6%) in the former and putaminal region (46.2%) in the latter (
P
<0.001). Intraventricular hemorrhage was more frequent in MMD-ICH than P-ICH (80.6% versus 20.4%,
P
<0.001). In MMD-ICH, primary intraventricular hemorrhage was more closely associated with prominent ipsilateral anterior choroidal artery than ICHs without intraventricular hemorrhage (75.0% versus 16.7%,
P
<0.001). Higher rates of rebleeding and infarction were observed in MMD-ICH than in age- and sex-matched patients with P-ICH.

Conclusions—
MMD-ICH may differ from P-ICH in hemorrhage location, generally presenting with intraventricular hemorrhage with or without ICH, which may be due to a prominent anterior choroidal artery. Patients with MMD may be more likely to experience recurrent bleeding and infarction.
Telestroke Ambulances in Prehospital Stroke Management
Authors: Liman Thomas G. , Winter Benjamin , Waldschmidt Carolin , Zerbe Norman , Hufnagl Peter , Audebert Heinrich J. , Endres Matthias 
Published: June 2012

Background and Purpose—
Pre- and intrahospital time delays are major concerns in acute stroke care. Telemedicine-equipped ambulances may improve time management and identify patients with stroke eligible for thrombolysis by an early prehospital stroke diagnosis. The aims of this study were (1) to develop a telestroke ambulance prototype; (2) to test the reliability of stroke severity assessment; and (3) to evaluate its feasibility in the prehospital emergency setting.

Methods—
Mobil, real-time audio–video streaming telemedicine devices were implemented into advanced life support ambulances. Feasibility of telestroke ambulances and reliability of the National Institutes of Health Stroke Scale assessment were tested using current wireless cellular communication technology (third generation) in a prehospital stroke scenario. Two stroke actors were trained in simulation of differing right and left middle cerebral artery stroke syndromes. National Institutes of Health Stroke Scale assessment was performed by a hospital-based stroke physician by telemedicine, by an emergency physician guided by telemedicine, and “a posteriori” on the basis of video documentation.

Results—
In 18 of 30 scenarios, National Institutes of Health Stroke Scale assessment could not be performed due to absence or loss of audio–video signal. In the remaining 12 completed scenarios, interrater agreement of National Institutes of Health Stroke Scale examination between ambulance and hospital and ambulance and “a posteriori” video evaluation was moderate to good with weighted κ values of 0.69 (95% CI, 0.51–0.87) and 0.79 (95% CI, 0.59–0.98), respectively.

Conclusion—
Prehospital telestroke examination was not at an acceptable level for clinical use, at least on the basis of the used technology. Further technical development is needed before telestroke is applicable for prehospital stroke management during patient transport.
Cavitation of Deep Lacunar Infarcts in Patients With First-Ever Lacunar Stroke
Authors: Loos Caroline M.J. , Staals Julie , Wardlaw Joanna M. , van Oostenbrugge Robert J. 
Published: June 2012

Background and Purpose—
Studies in patients with lacunar stroke often assess the number of lacunes. However, data on how many symptomatic lacunar infarcts cavitate into a lacune are limited. We assessed the evolution of symptomatic lacunar infarcts over 2-year follow-up.

Methods—
In 82 patients with first-ever lacunar stroke with a lacunar infarct in the deep brain regions (excluding the centrum semiovale), we performed a brain MR at presentation and 2 years later. We classified cavitation of lacunar infarcts at baseline and on follow-up MR as absent, incomplete, or complete. We recorded time to imaging, infarct size, and vascular risk factors.

Results—

On baseline MR, 38 (46%) index infarcts showed complete or incomplete cavitation. Median time to imaging was 8 (0–73) days in noncavitated and 63 (1–184) days in cavitated lesions (
P
<0.05). On follow-up imaging, 94% of the lacunar infarcts were completely or incompletely cavitated, most had reduced in diameter, and 5 (6%) had disappeared. Vascular risk factors were not associated with cavitation.

Conclusion—
Cavitation and lesion shrinkage were seen in almost all symptomatic lacunar infarcts in the deep brain regions over 2-year follow-up. Counting lacunes in these specific regions at a random moment might slightly, however not substantially, underestimate the burden of deep lacunar infarction.
Management of Hyoid Bone Fractures
Authors: Ramchand Tekchand , Choudhry Osamah J. , Shukla Pratik A. , Tomovic Senja , Kuperan Arjuna B. , Eloy Jean Anderson 
Published: June 2012

ObjectiveFractures of the hyoid bone are rare occurrences. They are mainly caused by strangulation/asphyxiation injuries, trauma to the neck, and motor vehicle accidents (MVAs). As a result of their rarity, proper treatment guidelines are not in place for dealing with these injuries. In this study, a systematic literature review was conducted with the goal of identifying optimal management for patients with fracture of the hyoid bone.Data SourcesMEDLINE and PubMed databases.Review MethodsThe MEDLINE and PubMed databases were searched for patients diagnosed with hyoid bone fracture. Further cases were obtained from the bibliographies of relevant articles. Full‐text articles were obtained. Patient presentation, method of diagnosis, treatment regimen, and outcomes are discussed.ResultsForty‐six cases were collected from 36 articles. No randomized controlled trials regarding treatment of hyoid fractures were found. The most common etiologies were MVA, assault, and neck trauma during athletic activities. Most common presenting symptoms included dysphagia, odynophagia, and pain upon neck rotation. Most frequent presenting signs included anterior neck tenderness and swelling. Five cases out of 46 had surgical repair of the fractured hyoid bone. In the remaining 41 cases, 26 were treated with conservative management, which included rest/observation, diet changes, and analgesia, while the other 15 cases required tracheotomy or surgical treatment for related injuries. All patients survived and had excellent outcomes with resolution of symptoms.ConclusionThis review shows that direct surgical treatment of hyoid fractures was performed in only 10.9% of cases. Both conservative and surgical management yielded positive outcomes.
Clinical Comparison of the Osteochondral Autograft Transfer System and Subchondral Drilling in Osteochondral Defects of the First Metatarsal Head
Authors: Kim Yong Sang , Park Eui Hyun , Lee Ho Jin , Koh Yong Gon , Lee Jin Woo 
Published: June 2012

Background: Osteochondral defects of the first metatarsal head can deteriorate to osteoarthritis of the first metatarsophalangeal joint if left untreated. Treatment options for osteochondral defects of the first metatarsal head vary widely. Purpose: To compare the clinical outcomes of the osteochondral autograft transfer system with those of subchondral drilling for the treatment of osteochondral defects of the first metatarsal head. Study Design: Cohort study; Level of evidence, 3. Methods: The authors retrospectively evaluated 24 cases of osteochondral defects of the first metatarsal head treated operatively; 14 patients underwent subchondral drilling (group A), while 10 were treated with the osteochondral autograft transfer system (group B). The association of variables of osteochondral defects with clinical outcomes was assessed in each group. Clinical outcomes were evaluated according to a visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scale, and the Roles and Maudsley score. The Tegner activity scale and an activity rating scale were used to determine the activity levels. Results: The mean VAS score in both groups was significantly improved (from 6.9 ± 0.9 to 3.9 ± 1.3 in group A and from 7.4 ± 0.8 to 3.4 ± 1.2 in group B; P < .05). No difference was noted between the 2 groups at final follow-up ( P = .651). The mean AOFAS score in both groups was significantly improved (from 62.9 ± 5.8 to 73.2 ± 8.2 in group A and from 65.0 ± 4.1 to 81.5 ± 5.8 in group B; P < .05). There was a significant difference in mean AOFAS score between the 2 groups at final follow-up ( P = .032). Large defect size (≥50 mm2) and the existence of a subchondral cyst were significant predictors of unsatisfactory clinical outcomes in group A ( P = .047 and P = .019, respectively). Multivariate analyses showed a defect size larger than 50 mm2 was associated with significantly worse outcomes on the last follow-up VAS and AOFAS scores in group A ( P = .005 for VAS and P = .006 for AOFAS). There was no association of defect size and subchondral cyst with clinical outcomes in group B ( P > .05). No association was found between location of the defect area and clinical outcome in either group. Conclusion: For osteochondral defects larger than 50 mm2 or when a subchondral cyst exists, the osteochondral autograft transfer system could potentially be used as a treatment of choice for osteochondral defects of the first metatarsal head to restore functionality of the metatarsophalangeal joint.
Tapping their Patients’ Problems Away?
Authors: Gaudiano Brandon A. , Brown Lily A. , Miller Ivan W. 
Published: June 2012

Objective: The objective was to learn about the characteristics of psychotherapists who use energy meridian techniques (EMTs). Methods: We conducted an Internet-based survey of the practices and attitudes of licensed psychotherapists. Results: Of 149 survey respondents (21.4% social workers), 42.3% reported that they frequently use or are inclined to use EMTs. EMT therapists reported higher use of a number of techniques from different theoretical orientations, reliance on intuition in decision making, positive attitudes toward complementary and alternative treatments, erroneous health beliefs, and importance placed on the intuitive appeal of evidence-based treatments. EMT therapists also had lower scores on a test of critical thinking. Conclusions: Results suggest that a number of characteristics differentiate therapists who are inclined to use EMTs, which can aid in future educational efforts.
Ceramic tiles based on central Tunisian clays (Sidi Khalif formation)
Authors: Medhioub M. , Hajjaji W. , Hachani M. , Lopez-Galindo A. , Rocha F. , Labrincha J. A. , Jamoussi F. 
Published: June 2012

AbstractThis study aims to find alternatives to some overexploited deposits in the north of Tunisia. The clays of the Sidi Khalif formation, of Uppermost Jurassic to Lower Cretaceous age, seem suitable to support this strategy, due to their abundance. In terms of mineralogy, they can be divided into two distinct groups, related to their palaeogeographic and eustatic contexts. The clays of the Sidi Khalif formation from Jebel Houareb (JH) and Jebel Meloussi (JM) are richer in clay minerals, while those of Jebel Rhouis (JR) and Jebel Boudinar (JB) zones are dolomite-rich. The compositional differences between the two groups influenced their technological behaviour in production of ceramic tiles. Upon firing, forsterite and gehlenite crystallized in the carbonate-rich JR and JB clays, whereas mullite formed in the JH and JM clays. Concerning their ceramic properties, the tiles made from JR or JB clays showed low bending strength and high water absorption. For JH and JM, the tiles had slightly greater mechanical resistance, but exhibited considerable linear shrinkage. These defects were partially corrected by introducing new formulations based on the same clays and by altering the firing cycles (HM1, HM2, RB1 and RB2). With these modifications, “Porcelanico” and “Monoporosa” technologically conforming tiles were obtained from HM2 and RB2 formulations, respectively.
Detailed clay mineralogy of the Triassic-Jurassic boundary section at Kendlbachgraben (Northern Calcareous Alps, Austria)
Authors: Zajzon N. , Kristály F. , Pálfy J. , Németh T. 
Published: June 2012

AbstractThe Triassic-Jurassic boundary (TJB) is marked by one of the five largest Phanerozoic mass extinctions. To constrain existing models for TJB events, we obtained a stratigraphically highly resolved dataset from a marine section at Kendlbachgraben, Austria.The topmost Triassic Kössen Formation contains low to medium-charged smectite and vermiculite as alteration products of mafic-ultramafic minerals. The clay minerals in the boundary mudstone are kaolinite ⩾ illite + muscovite ⨠ smectite > chlorite. Predominant kaolinite suggests humid climate and abundant terrigenous input. In the lowermost Jurassic, the clay mineral pattern changes to illite + muscovite ⨠ kaolinite ⨠ smectite, which reflects change to less humid and more moderate climate.The topmost Kössen Formation also contains clay spherules. Their composition, shape and size indicate that they are alteration products of airborne volcanic glass droplets solidified in the air, settled in the sea and altered rapidly with negligible transport in terrestrial or marine environments. Our data are consistent with sudden climatic change at the TJB, as a result of large-scale volcanic activity of the Central Atlantic Magmatic Province which produced distal airfall volcanic ash.
Clay minerals for nanocomposites and biotechnology: surface modification, dynamics and responses to stimuli
Authors: Heinz H. 
Published: June 2012

AbstractClay minerals find a wide range of application in composites, paints, drilling liquids, cosmetics, and medicine. This article reviews chemical and physical properties of natural and organically modified clay minerals to understand the nanometre-scale structure, surface characteristics, and application in functional materials. The relation between fundamental properties and materials design is emphasized and illustrated by examples. The discussion comprises the following: an overview; surface structure and cation density; solubility and solubility reversal by surface modification; the degree of covalent and ionic bonding represented by atomic charges; the distribution of metal substitution sites; measurements and simulations of interfacial properties at the nanometre scale; self-assembly, packing density, and orientation of alkylammonium surfactants on the clay mineral surface; the density and chain conformation of surfactants in organic interlayer spaces; the free energy of exfoliation in polymer matrices and modifications by tuning the cleavage energy; thermal transitions, diffusion, and optical responses of surfactants on the mineral surface; elastic moduli and bending stability of clay layers; and the adsorption mechanism of peptides onto clay mineral surfaces in aqueous solution. Potential applications in biotechnology and other future uses are described.