bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response–Effect Compatibility Defines the Natural Scrolling Direction
Authors: Chen Jing , Proctor Robert W. 
Published: March 2013

Objective: We evaluated alternative scrolling methods on non–touch screen computer operating systems by comparing human performance in different scrolling conditions. Background: The scrolling directions on current operating systems are discrepant. Few researchers have investigated how scrolling method influences users’ performance. The response–effect (R-E) compatibility principle can be used as a theoretical guide. Method: Experiments 1 and 2 involved two successive tasks (scrolling and target content judgment) to simulate how people scroll to acquire and use off-screen information. Performance in R-E compatible and incompatible conditions was compared. Experiment 3 involved a location judgment task to test the influence of target location. Experiments 4 and 5 included a scrolling effect following the location judgment task to test the sufficient role of the scrolling effect. Results: Overall, responses were facilitated when the response direction was compatible with the forthcoming display-content movement direction (an R-E compatibility effect), when the scrolling effect was task relevant or task irrelevant. A spatial stimulus–response (S-R) compatibility effect attributable to target location was also found. When the scrolling effect was present, there were both R-E and S-R components; the R-E effect was the larger of the two. Conclusion: Scrolling in the direction of content movement yielded the best performance, and the scrolling effect was the main source of the R-E compatibility effect. Application: These findings suggest that (a) the R-E compatibility principle may be used as a general design guideline for scrolling and (b) a consistent scrolling method should be available on various operating systems.
Prospective Open-Label, Single-Arm, Multicenter, Safety, Tolerability, and Pharmacokinetic Studies of Intravenous Levetiracetam in Children With Epilepsy
Authors: Weinstock Arie , Ruiz Matilde , Gerard Danielle , Toublanc Nathalie , Stockis Armel , Farooq Osman , Dilley Deanne , Karmon Yuval , Elgie Mary Jo , Schiemann-Delgado Jimmy 
Published: March 2013

Levetiracetam given via intravenous administration has been shown to be an effective alternative in adults with epilepsy when oral administration is not feasible. This study was a prospective single-arm, multicenter study to assess tolerability, safety, and pharmacokinetics of intravenous levetiracetam in children with epilepsy. Children with epilepsy ages 1 month to 16 years requiring intravenous levetiracetam were enrolled. Assessments included vital signs, electrocardiogram, hematology, chemistry, plasma concentrations of antiepileptic medications, weight, physical/neurological examinations, and pharmacokinetics. A total of 52 patients were enrolled. Mild to moderate treatment-emergent adverse events occurred in 63%, the most frequent being pyrexia and dry mouth. Most other treatment-emergent adverse events were considered unrelated to intravenous levetiracetam administration. Therefore, intravenous levetiracetam in the acute setting was overall well tolerated in children 1 month to 16 years.
Methods for Improving the Quality of Palliative Care Delivery
Authors: Lau Brandyn D. , Aslakson Rebecca A. , Wilson Renee F. , Fawole Oluwakemi A. , Apostol Colleen C. , Martinez Kathryn A. , Vollenweider Daniela , Bass Eric B. , Dy Sydney E. Morss 
Published: March 2013

Background: The effectiveness for improving the outcomes across palliative care domains remains unclear. We conducted a systematic review of different types of quality improvement interventions relevant to palliative care. Methods: We searched PubMed, CINAHL, PsycINFO, and Cochrane for relevant articles published between 2000 and 2011. Results: A total of 10 randomized controlled trials and 7 nonrandomized controlled trials were included. Of the 5 studies using relay of clinical information, 1 reported significant improvement in patient quality of life. Of the 5 studies targeting education and self-management, 4 found significant improvements in quality of life or patient symptoms. Conclusion: A minority of quality improvement interventions have succeeded in improving the quality of palliative care delivery. More studies are needed on specific quality improvement types, including organizational change and multiple types of interventions.
Central Calcaneal Osteotomy for Correction of Flexible Pes Planovalgus Deformity
Authors: Klaue Kaj , Kaliyaperumal Kannan , Swanson Scott A. , Low Wilson Cong Jin 
Published: March 2013

Background: Lateral column lengthening procedures have been extensively reported either as primary procedures or adjuncts to combined soft tissue procedures and osteotomies for the correction of the pes planovalgus deformity. There is also considerable debate as to the ideal procedure that is not followed by recurrence and obviates the need for revision surgeries and minimizes complications. We describe a technique and present the clinical results of lateral column lengthening that provides a powerful correction to restore normal foot alignment. Methods: We retrospectively reviewed 26 feet in 21 patients with a mean age of 35.4 years (range, 12-75) over an average follow-up period of 71 months (range, 12-147) who underwent reconstructive surgery for flexible pes planovalgus foot. The reconstructive procedures included a central calcaneal osteotomy in all patients, a medial column stabilization procedure, flexor digitorium transfer (FDL), and a gastrocnemius or Achilles tendon lengthening. Clinical evaluation was carried out with the AOFAS ankle-hindfoot scores. Standard weight-bearing anterior posterior (AP) and lateral radiographs before surgery and at follow-up were analyzed for radiographic parameters of correction. Results: The median AOFAS score increased from 50 to 90. Two patients reported dissatisfaction with the result. There were no nonunions nor complications related to hardware. Radiographic improvement of the talonavicular coverage angle was a 74% change from baseline value. All radiographic parameters improved ( P < .001) except the lateral talocalcaneal angle ( P = .48). No secondary subsidence of the arch was observed within the follow-up time. Conclusion: Correction of flexible pes planovalgus deformity with a central calcaneal osteotomy was an effective, reproducible method to restore normal foot alignment and good function. Level of Evidence: Level IV, retrospective case series.
MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor
Authors: Chakraborty Arup R. , Robey Robert W. , Luchenko Victoria L. , Zhan Zhirong , Piekarz Richard L. , Gillet Jean-Pierre , Kossenkov Andrew V. , Wilkerson Julia , Showe Louise C. , Gottesman Michael M. , Collie Nathan L. , Bates Susan E. 
Published: March 2013

Key Points
MAPK pathway activation and Bim loss may represent a fundamental mechanism of resistance to histone deacetylase inhibitors. Combination of romidepsin with an MEK inhibitor may lead to greater responses in cancers in which the MAPK pathway is active.
Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium
Authors: Yuan Lei , Janes Lauren , Beeler David , Spokes Katherine C. , Smith Joshua , Li Dan , Jaminet Shou-Ching , Oettgen Peter , Aird William C. 
Published: March 2013

Key PointsRNA splicing of the first intron of the von Willebrand factor gene is essential for expression in the endothelium. RNA splicing may play a role in mediating endothelial cell heterogeneity.
Endothelial RAF1/ERK activation regulates arterial morphogenesis
Authors: Deng Yong , Larrivée Bruno , Zhuang Zhen W. , Atri Deepak , Moraes Filipa , Prahst Claudia , Eichmann Anne , Simons Michael 
Published: March 2013

Key PointsRAF1 Ser259 phosphorylation is a critical regulator step controlling arterial morphogenesis and arterial-venous patterning. ERK activation controls DLL4/Notch signaling and semaphorin 6A–mediated endothelial cell repulsion.
Chengia laxispicatagen. et sp. nov., a new ephedroid plant from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China: evolutionary, taxonomic, and biogeographic implications
Authors: Yang Yong , Lin Longbiao , Wang Qi 
Published: March 2013

AbstractBackgroundThe extant Gnetales include three monotypic families, namely, Ephedraceae (Ephedra), Gnetaceae (Gnetum), and Welwitschiaceae (Welwitschia), all of which possess compound female cones that comprise a main axis and 1 to multiple pairs/whorls of bracts subtending a female reproductive unit or having lower pairs/whorls of bracts sterile. However, the evolutionary origin of such a reproductive architecture in Gnetales is controversial in the light of the competing anthophyte versus gnetifer hypotheses of seed plant relationships. Hence, macrofossils demonstrating the structure of compound female cones of the Gnetales should be important to decipher the early evolution of the order.ResultsA new ephedroid plantChengia laxispicatagen. et sp. nov. is described from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China. The fossil represents a part of a leafy shooting system with reproductive organs attached. The main shoot bears internodes and swollen nodes, from which lateral branches arise oppositely. Reproductive organs consist of female spikes terminal to twigs or axillary to linear leaves. Spikes are loosely arranged, having prominent nodes and internodes. Bracts of the spikes are decussately opposite and comprise 4—8 pairs of bracts. Each bract subtends an ellipsoid seed. Seeds are sessile, with a thin outer envelope and a distal micropylar tube.ConclusionsChengia laxispicatagen. et sp. nov. provides a missing link between archetypal fertile organs in the crown lineage of the Gnetales and compound female cones of the extant Ephedraceae. Combined with a wealth ofEphedraand ephedroid macrofossils from the Early Cretaceous, we propose a reduction and sterilization hypothesis that the female cone of the extant Ephedraceae may have stemmed from archetypal fertile organs in the crown lineage of the Gnetales. These have undergone sequentially intermediate links similar to female cones of CretaceousSiphonospermum, Chengia, andLiaoxiaby reduction and sterilization of the lower fertile bracts, shortenings of internodes and peduncles as well as loss of reproductive units in all inferior bracts. The basal family Ephedraceae includingEphedraof the extant Gnetales was demonstrated to have considerable diversity by the Early Cretaceous, so an emended familial diagnosis is given here. The Jehol Biota in Northeast China and adjacent areas contains a plethora of well-preserved macrofossils ofEphedraand ephedroids that show different evolutionary stages including primitive and derived characters of Ephedraceae, so Northeast China and adjacent areas may represent either the centre of origination or one of the centres for early diversification of the family.
Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb
Authors: Hori Kazuichiro , Tsujii Masaya , Iino Takahiro , Satonaka Haruhiko , Uemura Takeshi , Akeda Koji , Hasegawa Masahiro , Uchida Atsumasa , Sudo Akihiro 
Published: March 2013

Abstract

Background
Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles.

Methods
C57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis.

Results
This model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression.

Conclusions
Edaravone was found to have a protective effect against I/R injury by directly inhibiting lipid peroxidation of the myocyte by free radicals in skeletal muscles and may also reduce the secondary edema and inflammatory infiltration incidence of oxidative stress on tissue.
cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by bumetanide in semicircular canal duct epithelium
Authors: Pondugula Satyanarayana R , Kampalli Suresh B , Wu Tao , De Lisle Robert C , Raveendran Nithya N , Harbidge Donald G , Marcus Daniel C 
Published: March 2013

Abstract

Background
The vestibular system controls the ion composition of its luminal fluid through several epithelial cell transport mechanisms under hormonal regulation. The semicircular canal duct (SCCD) epithelium has been shown to secrete Cl- under β2-adrenergic stimulation. In the current study, we sought to determine the ion transporters involved in Cl- secretion and whether secretion is regulated by PKA and glucocorticoids.

Results
Short circuit current (I

sc
) from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 μM), 8-Br-cAMP (EC50: 180 μM), 8-pCPT-cAMP (100 μM), IBMX (250 μM), and RO-20-1724 (100 μM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated I

sc
. Partial inhibition of stimulated I

sc
individually by bumetanide (10 & 50 μM), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 μM) were additive and complete. Stimulated I

sc
was also partially inhibited by CFTRinh-172 (5 & 30 μM), flufenamic acid (5 μM) and diphenylamine-2,2′-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR+/− mice showed a stimulation of Isc from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR−/− mice had no responses. Nonetheless, CFTR−/− mice showed no difference from CFTR+/− mice in their ability to balance (rota-rod). Stimulated I

sc
was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 & 0.3 μM), prednisolone (0.3, 1 & 3 μM), hydrocortisone (0.01, 0.1 & 1 μM), and corticosterone (0.1 & 1 μM) and mineralocorticoid aldosterone (1 μM). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.

Conclusions
These results are consistent with a model of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+-K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the regulation of Cl- secretion by protein kinase A and glucocorticoids.
MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1
Authors: Creevey Laura , Ryan Jacqueline , Harvey Harry , Bray Isabella M , Meehan Maria , Khan Adnan R , Stallings Raymond L 
Published: March 2013

Abstract

Background
Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive of neuroblastoma patient survival and has been reported as a tumor suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of the cell cycle and predicted target of miR-497, has emerged as an oncogene in several cancer types and therefore represents an attractive potential target for novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate the potential tumor suppressive role of miR-497 in high-risk neuroblastoma.

Methods
Expression levels of miR-497 and WEE1 in tissues and cells were determined using RT-PCR. The effect of miR-497 and siWEE1 on cell viability was evaluated using MTS assays, apoptosis levels were determined using FACS analysis of Annexin V/PI stained cells, and target protein expression was determined using western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean±S.E.M and differences were tested for significance using 2-tailed Students t-test.

Results
We determined that miR-497 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and that low miR-497 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma. Furthermore, our analysis showed that high WEE1 levels are significantly associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1 in MNA cell lines results in significant levels of apoptosis, supporting an oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR-497 over-expressing cells and WEE1 inhibited cells, resulted in a significant increase in apoptosis in MNA cells, describing a synergistic effect and therefore a potential therapeutic for high-risk neuroblastoma.

Conclusion
Our study’s results are consistent with miR-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. These findings re-enforce the proposal of WEE1 as a therapeutic target in neuroblastoma.
Targeting p53 by small molecules in hematological malignancies
Authors: Saha Manujendra N , Qiu Lugui , Chang Hong 
Published: March 2013

Abstractp53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their anti-tumor effects in different types of hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully reached the stage of phase I/II clinical trials in at least one type of hematological cancer. Thus, the pharmacological activation of p53 by these small molecules has a major clinical impact on prognostic use and targeted drug design. In the current review, we present the recent achievements in p53 research using small molecules in hematological malignancies. Anticancer activity of different classes of compounds targeting the p53 signaling pathway and their mechanism of action are discussed. In addition, we discuss how p53 tumor suppressor protein holds promise as a drug target for recent and future novel therapies in these diseases.
Germline deletion of β2 microglobulin or CD1d reduces anti-phospholipid antibody, but increases autoantibodies against non-phospholipid antigens in the NZB/W F1 model of lupus
Authors: Singh Ram Raj , Yang Jun-Qi , Kim Peter J , Halder Ramesh C 
Published: March 2013

Abstract
Introduction
β2-microglobulin (β2m) is required for the surface expression of MHC class I and class I-like proteins such as CD1d, Qa1 and neonatal Fc receptor (FcRn), all of which may impact the development of autoimmunity. Since CD1d is known to bind and present phospholipid antigens to T cells, we asked if the deficiency of β2m or CD1d will impact the development of anti-phospholipid antibodies as compared to other aspects of lupus autoimmunity.

Methods
We introgressed the β2m-null genotype onto the NZB and NZW backgrounds for 12 to 14 generations to generate genetically lupus-susceptible (NZB/NZW)F1 (BWF1) mice that are β2m-deficient (β2m°). Circulating immunoglobulins (Ig), rheumatoid factor (RF), anti-DNA and anti-cardiolipin (anti-CL) antibodies, and renal disease were analyzed in these and CD1d-deficient (CD1d°) BWF1 mice that we had previously generated.

Results
Whereas β2m° BWF1 mice had reduced serum IgG, they had increased mortality, nephritis, serum IgG anti-DNA antibody and RF as compared to heterozygous and wild-type littermates. These effects were recapitulated in CD1d° BWF1 mice, except that they also had increased serum IgG as compared to control littermates. Intriguingly, both β2m° and CD1d° mice had lower serum anti-CL antibody levels than in control littermates. Such CD1d dependence of anti-CL antibody production is not mediated by CD1d/glycolipid-reactive iNKT cells, as these cells reduced the production of RF and anti-DNA antibodies but had no effect on anti-CL antibodies.

Conclusions
We report a novel dichotomous role of β2m and CD1d, whereby these molecules differently regulate autoimmunity against phospholipid versus non-phospholipid autoantigens.
Estimation of optic nerve sheath diameter on an initial brain computed tomography scan can contribute prognostic information in traumatic brain injury patients
Authors: Legrand Aurélien , Jeanjean Patrick , Delanghe Fanny , Peltier Johann , Lecat Benoit , Dupont Hervé 
Published: March 2013

Abstract
Introduction
The aim of this study was to evaluate the prognostic value of optic nerve sheath diameter (ONSD) measured on the initial brain computed tomography (CT) scan for intensive care unit (ICU) mortality in severe traumatic brain injury (TBI) patients.

Methods
A prospective observational study of all severe TBI patients admitted to a neurosurgical ICU (over a 10-month period). Demographic and clinical data and brain CT scan results were recorded. ONSD for each eye was measured on the initial CT scan. The group of ICU survivors was compared to non-survivors. Glasgow Outcome Scale (GOS) was evaluated six months after ICU discharge.

Results
Seventy-seven patients were included (age: 43 ± 18; 81% males; mean Injury Severity Score: 35 ± 15; ICU mortality: 28.5% (n = 22)). Mean ONSD on the initial brain CT scan was 7.8 ± 0.1 mm in non-survivors vs. 6.8 ± 0.1 mm in survivors (P < 0.001). The operative value of ONSD was a good predictor of mortality (area under the curve: 0.805). An ONSD cutoff ≥ 7.3 had a sensitivity of 86.4% and a specificity of 74.6% and was independently associated with mortality in this population (adjusted odds ratio 95% confidence interval: 22.7 (3.2 to 159.6), P = 0.002). There was a relationship between initial ONSD values and six-month GOS (P = 0.03).

Conclusions
ONSD measured on the initial brain CT scan is independently associated with ICU mortality rate (when ≥ 7.3 mm) in severe TBI patients.
See related commentary by Masquère et al.,http://ccforum.com/content/17/3/151