bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Detection of Glutamate Predicts Survival in Pediatric Medulloblastoma
Authors: Wilson Martin , Gill Simrandip K. , MacPherson Lesley , English Martin , Arvanitis Theodoros N. , Peet Andrew C. 
Published: June 2014

Abstract
Purpose: Medulloblastoma is the most common malignant brain tumor occurring in childhood and is a significant cause of morbidity and mortality in pediatric oncology. More intense treatment strategies are recommended for patients displaying high-risk factors; however, considerable variation in outcome remains, indicating a need for improved predictive markers. In this study, 1H magnetic resonance spectroscopy (MRS) was used to investigate noninvasive molecular biomarkers of survival in medulloblastoma.
Experimental Design: MRS was performed on a series of 35 biopsy-confirmed medulloblastoma cases. One case was excluded because of poor quality MRS. The prognostic value of MRS detectable biomarkers was investigated using Cox regression, retrospectively (N = 15). A subsequent validation analysis (N = 19) was also performed to reduce the chance of type I errors. Where available, high-resolution ex vivo MRS of biopsy tissue was used to confirm biomarker assignments.
Results: The retrospective analysis revealed that creatine, glutamate, and glycine were markers of survival (P &lt; 0.01). The validation analysis showed that glutamate was a robust marker, with a hazard ration (HR) of 8.0 for the full dataset (P = 0.0003, N = 34). A good correlation between in vivo and ex vivo MRS glutamate/total-choline was found (P = 0.001), validating the in vivo assignment. Ex vivo glutamate/total-choline was also associated with survival (P &lt; 0.01).
Conclusion: The identification of glutamate as a predictive biomarker of survival in pediatric medulloblastoma provides a clinically viable risk factor and highlights the importance of more detailed studies into the metabolism of this disease. Noninvasive biomarker detection using MRS may offer improved disease monitoring and potential for widespread use following multicenter validation. Clin Cancer Res; 20(17); 4532–9. ©2014 AACR.
The Combination of Circulating Ang1 and Tie2 Levels Predicts Progression-Free Survival Advantage in Bevacizumab-Treated Patients with Ovarian Cancer
Authors: Backen Alison , Renehan Andrew G. , Clamp Andrew R. , Berzuini Carlo , Zhou Cong , Oza Amit , Bannoo Selina , Scherer Stefan J. , Banks Rosamonde E. , Dive Caroline , Jayson Gordon C. 
Published: June 2014

Abstract
Purpose: Randomized ovarian cancer trials, including ICON7, have reported improved progression-free survival (PFS) when bevacizumab was added to conventional cytotoxic therapy. The improvement was modest prompting the search for predictive biomarkers for bevacizumab.
Experimental Design: Pretreatment training (n = 91) and validation (n = 114) blood samples were provided by ICON7 patients. Plasma concentrations of 15 angio-associated factors were determined using validated multiplex ELISAs. Our statistical approach adopted PFS as the primary outcome measure and involved (i) searching for biomarkers with prognostic relevance or which related to between-individual variation in bevacizumab effect; (ii) unbiased determination of cutoffs for putative biomarker values; (iii) investigation of biologically meaningfully predictive combinations of putative biomarkers; and (iv) replicating the analysis on candidate biomarkers in the validation dataset.
Results: The combined values of circulating Ang1 (angiopoietin 1) and Tie2 (Tunica internal endothelial cell kinase 2) concentrations predicted improved PFS in bevacizumab-treated patients in the training set. Using median concentrations as cutoffs, high Ang1/low Tie2 values were associated with significantly improved PFS for bevacizumab-treated patients in both datasets (median, 23.0 months vs. 16.2; P = 0.003) for the interaction of Ang1–Tie2 treatment in Cox regression analysis. The prognostic indices derived from the training set also distinguished high and low probability for progression in the validation set (P = 0.008), generating similar values for HR (0.21 vs. 0.27) between treatment and control arms for patients with high Ang1 and low Tie2 values.
Conclusions: The combined values of Ang1 and Tie2 are predictive biomarkers for improved PFS in bevacizumab-treated patients with ovarian cancer. These findings need to be validated in larger trials due to the limitation of sample size in this study. Clin Cancer Res; 20(17); 4549–58. ©2014 AACR.
Phase I Expansion and Pharmacodynamic Study of the Oral MEK Inhibitor RO4987655 (CH4987655) in Selected Patients with Advanced Cancer with RAS–RAF Mutations
Authors: Zimmer Lisa , Barlesi Fabrice , Martinez-Garcia Maria , Dieras Veronique , Schellens Jan H.M. , Spano Jean-Philippe , Middleton Mark R. , Calvo Emiliano , Paz-Ares Luiz , Larkin James , Pacey Simon , Venturi Miro , Kraeber-Bodéré Françoise , Tessier Jean J.L. , Eberhardt Wilfried Ernst Erich , Paques Michel , Guarin Ernesto , Meresse Valerie , Soria Jean-Charles 
Published: June 2014

Abstract
Purpose: This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor.
Experimental Design: We undertook a multicenter phase I two-part study (dose escalation and cohort expansion). Here, we present the part 2 expansion that included melanoma, non–small cell lung cancer (NSCLC), and colorectal cancer with oral RO4987655 administered continuously at recommended doses of 8.5 mg twice daily until progressive disease (PD). Sequential tumor sampling investigated multiple markers of pathway activation/tumor effects, including ERK phosphorylation and Ki-67 expression. BRAF and KRAS testing were implemented as selection criteria and broader tumor mutational analysis added.
Results: Ninety-five patients received RO4987655, including 18 BRAF-mutant melanoma, 23 BRAF wild-type melanoma, 24 KRAS-mutant NSCLC, and 30 KRAS-mutant colorectal cancer. Most frequent adverse events were rash, acneiform dermatitis, and gastrointestinal disorders, mostly grade 1/2. Four (24%) of 17 BRAF-mutated melanoma had partial response as did four (20%) of 20 BRAF wild-type melanoma and two (11%) of 18 KRAS-mutant NSCLC. All KRAS-mutant colorectal cancer developed PD. Paired tumor biopsies demonstrated reduced ERK phosphorylation among all cohorts but significant differences among cohorts in Ki-67 modulation. Sixty-nine percent showed a decrease in fluorodeoxyglucose uptake between baseline and day 15. Detailed mutational profiling confirmed RAS/RAF screening and identified additional aberrations (NRAS/non-BRAF melanomas; PIK3CA/KRAS colorectal cancer) without therapeutic implications.
Conclusions: Safety profile of RO4987655 was comparable with other MEK inhibitors. Single-agent activity was observed in all entities except colorectal cancer. Evidence of target modulation and early biologic activity was shown among all indications independent of mutational status. Clin Cancer Res; 20(16); 4251–61. ©2014 AACR.
Endothelial Deletion of Phospholipase D2 Reduces Hypoxic Response and Pathological Angiogenesis
Authors: Ghim Jaewang , Moon Jin-Sook , Lee Chang Sup , Lee Junyeop , Song Parkyong , Lee Areum , Jang Jin-Hyeok , Kim Dayea , Yoon Jong Hyuk , Koh Young Jun , Chelakkot Chaithanya , Kang Byung Jun , Kim Jung-Min , Kim Kyung Lock , Yang Yong Ryoul , Kim Youngmi , Kim Sun-Hee , Hwang Daehee , Suh Pann-Ghill , Koh Gou Young , Kong Young-Yun , Ryu Sung Ho 
Published: June 2014

Objective—
Aberrant regulation of the proliferation, survival, and migration of endothelial cells (ECs) is closely related to the abnormal angiogenesis that occurs in hypoxia-induced pathological situations, such as cancer and vascular retinopathy. Hypoxic conditions and the subsequent upregulation of hypoxia-inducible factor-1α and target genes are important for the angiogenic functions of ECs. Phospholipase D2 (PLD2) is a crucial signaling mediator that stimulates the production of the second messenger phosphatidic acid. PLD2 is involved in various cellular functions; however, its specific roles in ECs under hypoxia and in vivo angiogenesis remain unclear. In the present study, we investigated the potential roles of PLD2 in ECs under hypoxia and in hypoxia-induced pathological angiogenesis in vivo.

Approach and Results—

Pld2
knockout ECs exhibited decreased hypoxia-induced cellular responses in survival, migration, and thus vessel sprouting. Analysis of hypoxia-induced gene expression revealed that PLD2 deficiency disrupted the upregulation of hypoxia-inducible factor-1α target genes, including
VEGF
,
PFKFB3
,
HMOX-1
, and
NTRK2
. Consistent with this, PLD2 contributed to hypoxia-induced hypoxia-inducible factor-1α expression at the translational level. The roles of PLD2 in hypoxia-induced in vivo pathological angiogenesis were assessed using oxygen-induced retinopathy and tumor implantation models in endothelial-specific
Pld2
knockout mice.
Pld2
endothelial-specific knockout retinae showed decreased neovascular tuft formation, despite a larger avascular region. Tumor growth and tumor blood vessel formation were also reduced in
Pld2
endothelial-specific knockout mice.

Conclusions—
Our findings demonstrate a novel role for endothelial PLD2 in the survival and migration of ECs under hypoxia via the expression of hypoxia-inducible factor-1α and in pathological retinal angiogenesis and tumor angiogenesis in vivo.
Cerebrovascular Events in 21 105 Patients With Atrial Fibrillation Randomized to Edoxaban Versus Warfarin
Authors: Giugliano Robert P. , Ruff Christian T. , Rost Natalia S. , Silverman Scott , Wiviott Stephen D. , Lowe Cheryl , Deenadayalu Naveen , Murphy Sabina A. , Grip Laura T. , Betcher Joshua M. , Duggal Anil , Dave Jay , Shi Minggao , Mercuri Michele , Antman Elliott M. , Braunwald Eugene 
Published: June 2014

Background and Purpose—
The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate–high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously.

Methods—
We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose). The primary end point for this prespecified analysis of cerebrovascular events was all stroke (ischemic plus hemorrhagic), defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting ≥24 hours or fatal in <24 hours. Independent stroke neurologists unaware of treatment adjudicated all cerebrovascular events.

Results—

Patients randomized to high-dose edoxaban had fewer strokes on-treatment (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) than warfarin (median time-in-therapeutic range, 68.4%); patients in the low-dose edoxaban group had similar rates (hazard ratio, 1.10 versus warfarin; 95% confidence interval, 0.91–1.32). Rates of ischemic stroke or transient ischemic attack were similar with high-dose edoxaban (1.76% per year) and warfarin (1.73% per year;
P
=0.81), but more frequent with low-dose edoxaban (2.48% per year;
P
<0.001). Both edoxaban regimens significantly reduced hemorrhagic stroke and other subtypes of intracranial bleeds.

Conclusions—
In patients with atrial fibrillation, once-daily edoxaban was as effective as warfarin in preventing all strokes, with significant reductions in various subtypes of intracranial bleeding. Ischemic cerebrovascular event rates were similar with high-dose edoxaban and warfarin, whereas low-dose edoxaban was less effective than warfarin.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00781391.
<span lang="EN-GB">Notes on Early Land Plants Today. 58. Historical circumscription of Schistochilaceae (Marchantiophyta) and a new combination in Schistochila</span>
Authors: He Xiaolan , Glenny David , Söderström Lars , Hagborg Anders , Von Konrat Matt 
Published: June 2014

The family Schistochilaceae Buch (1928: 9) consists of approximately 80 extant species. More than two-thirds of its diversity occurs in temperate to subantarctic South America and Australasia, and nearly one third in the tropical mountain forests of Southeast Asia and the western Pacific Islands. The plants of Schistochilaceae are usually robust and form a prominent component of the ground layer of cool temperate forests or upper montane tropical forests, commonly forests in which Nothofagus is a dominant genus. The first species of the family, published as Jungermannia appendiculata Hooker (1818: tab. 15), Jungermannia glaucescens Hooker (1818: tab. 39), Jungermannia lamellata Hooker (1818: tab. 49), Jungermannia nobilis Hooker (1818: tab. 11), Jungermannia sphagnoides Schwägrichen (1814: 23) and Jungermannia thouarsii Hooker (1818: tab. 48), were described during 1814–1818. Dumortier established the genus Schistochila Dumortier (1835: 15) to accommodate the above mentioned species except Jungermannia glaucescens and Jungermannia sphagnoides, but he also added one new species, Schistochila pinnatifolia Dumortier (1835: 15) nom. inval. (ICN Art. 38.1(a); no description; McNeill et al. 2012). The definition of Schistochilaceae has remained largely unchanged since it was separated from Scapaniaceae Migula (1904: 479) by Buch (1928) and then later Balantiopsaceae Buch (1955: 23). The presence of magenta rhizoids, winged and complicate-bilobed leaves with smaller dorsal lobes, a shoot calyptra elaborated into a well-developed coelocaule, and a cylindrical sporophyte capsule with straight valves generally defines the family. These features, to a great extent, isolate Schistochilaceae from the rest of the leafy liverworts. Therefore, taxonomic rearrangements or revisions, based on morphological investigations, have mostly been at generic level or below (Grolle 1966, 1968, Hässel 1973, Schuster 1971a, Schuster & Engel 1977, 1985). So far, taxonomic revisions have only been done at regional scales, a study at global scale is under way (Glenny et al., unpublished).
Morphological diversity and genetic structure within Lerista kalumburu Storr, 1976 (Squamata: Scincomorpha: Sphenomorphidae)—taxonomic implications
Authors: AMEY ANDREW P. , WILMER JESSICA WORTHINGTON 
Published: June 2014

Discovery of a population of two-toed Lerista allied to L. kalumburu prompted a morphological and genetic examination of this taxon. Molecular analysis showed limited divergence and paraphyly of three-toed populations with respect to the two-toed form. We contend that these populations are best viewed as a single species exhibiting remarkable diversity in limb morphology. As this prevents successfully identifying the taxon using published keys, we provide a new diagnosis and a redescription of the species.
Caregiver burden is associated with disability in schizophrenia: Results of a study from a rural setting of south India
Authors: Kumar Channaveerachari N , Suresha Kudumallige K , Thirthalli Jagadisha , Arunachala Udupi , Gangadhar Bangalore N 
Published: June 2014

Background: Taking care of patients with schizophrenia is a major source of burden to the family. Research on burden experienced by family members of patients living in rural communities is sparse. Methods: Data were obtained from a community intervention program for psychoses in a rural community of south India, where persons with severe mental disorders were identified, treated and followed up. As part of the program, caregivers of 245 schizophrenia patients were interviewed using the Burden Assessment Schedule. Psychopathology (Positive and Negative Syndrome Scale; PANSS), treatment status and disability (Indian Disability Evaluation and Assessment Scale; IDEAS) experienced by the patients were also assessed. Univariate and multivariate analyses were used to study the influence of different factors on the caregiver burden. Results: Level of burden had a significant direct correlation with disability (Pearson’s r = .35; p < .01) and severity of psychopathology ( r = .21; p < .01). Duration of treatment had an inverse correlation with burden (Pearson’s r = −.16; p < .01). Multivariate analysis revealed that total IDEAS score (Beta = .28; t = 4.37; p ≤ .01), duration of treatment (Beta = −.17; t = −2.58; p = .01), age of the family caregiver (Beta = .15; t = 2.4; p = .02) and gender of the patient (Beta = −.13; t = −2.1; p = .04) were significant predictors of burden. The model including total IDEAS score explained 14% of variance (adjusted R2 = .139; p < .01). Conclusion: Burden experienced by family caregivers of schizophrenia patients depends on the level of disability experienced by the patient, age of the family caregivers and gender of the patient. Interventions to reduce disability of the patients may reduce the caregiver burden.
Intracranial Facial Nerve Crush Injury and Facial Motor Nuclei Cell Loss in Rats
Authors: Amine Muhamad , Foecking Eileen M. , Marzo Sam J. 
Published: June 2014

ObjectivesThe purpose of this study was to (1) assess the degree of motoneuron cell loss and (2) the combinatorial effects of electrical stimulation (ES) and testosterone propionate (TP) on cell survival following an intracranial facial nerve crush injury and (3) compare these results to distal injuries.Study DesignProspective, randomized, controlled animal study.MethodsSprague‐Dawley rats were randomly divided into 3 groups: intracranial sham surgery or intracranial crush injury with or without ES and TP treatments. The intracranial sham group underwent exposure of the meatal segment of the right facial nerve. The intracranial crush groups underwent a crush of the meatal segment following exposure with or without ES and TP treatment immediately following the injury and followed for 8 weeks. Brain sections were thionin‐stained, and facial motor nuclei (FMN) were counted using light microscopy. Results were compared to intratemporal and extracranial facial nerve crush injuries.ResultsIntracranial crush injury resulted in a significant decrease in cell survival (n = 6) of 65.6% as compared to the sham group (99.4%; n = 9). The treatments increased cell survival to 93.8% (n = 2). The cell loss in the intracranial facial nerve injury is more substantial than the intratemporal (85.8%; n = 7) and extracranial (103.3%; n = 4) injuries.ConclusionsIntracranial injury results in a more profound cell loss compared to the distal injuries. These data suggest a critical importance for the development of treatment modalities that can help improve cell survival following facial nerve injuries.
The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial
Authors: Schramko A , Suojaranta-Ylinen R , Niemi T , Pesonen E , Kuitunen A , Raivio P , Salmenperä M 
Published: June 2014

Introduction: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. Materials and methods: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. Results: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). Conclusions: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.
Dose reduction for chest CT: comparison of two iterative reconstruction techniques
Authors: Pourjabbar Sarvenaz , Singh Sarabjeet , Kulkarni Naveen , Muse Victorine , Digumarthy Subba R , Khawaja Ranish Deedar Ali , Padole Atul , Do Synho , Kalra Mannudeep K 
Published: June 2014

Background Lowering radiation dose in computed tomography (CT) scan results in low quality noisy images. Iterative reconstruction techniques are used currently to lower image noise and improve the quality of images. Purpose To evaluate lesion detection and diagnostic acceptability of chest CT images acquired at CTDIvol of 1.8 mGy and processed with two different iterative reconstruction techniques. Material and Methods Twenty-two patients (mean age, 60 ± 14 years; men, 13; women, 9; body mass index, 27.4 ± 6.5 kg/m2) gave informed consent for acquisition of low dose (LD) series in addition to the standard dose (SD) chest CT on a 128 - multidetector CT (MDCT). LD images were reconstructed with SafeCT C4, L1, and L2 settings, and Safire S1, S2, and S3 settings. Three thoracic radiologists assessed LD image series (S1, S2, S3, C4, L1, and L2) for lesion detection and comparison of lesion margin, visibility of normal structures, and diagnostic confidence with SD chest CT. Inter-observer agreement (kappa) was calculated. Results Average CTDIvol was 6.4 ± 2.7 mGy and 1.8 ± 0.2 mGy for SD and LD series, respectively. No additional lesion was found in SD as compared to LD images. Visibility of ground-glass opacities and lesion margins, as well as normal structures visibility were not affected on LD. CT image visibility of major fissure and pericardium was not optimal in some cases ( n = 5). Objective image noise in some low dose images processed with SafeCT and Safire was similar to SD images ( P value > 0.5). Conclusion Routine LD chest CT reconstructed with iterative reconstruction technique can provide similar diagnostic information in terms of lesion detection, margin, and diagnostic confidence as compared to SD, regardless of the iterative reconstruction settings.