bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Antitumor Therapy with Metronomic Topotecan and Hypoxia-Activated Prodrug, Evofosfamide, in Neuroblastoma and Rhabdomyosarcoma Preclinical Models
Authors: Zhang Libo , Marrano Paula , Wu Bing , Kumar Sushil , Thorner Paul , Baruchel Sylvain 
Published: December 2015

Abstract
Purpose: Tumor cells residing in tumor hypoxic zones are a major cause of drug resistance and tumor relapse. In this study, we investigated the efficacy of evofosfamide, a hypoxia-activated prodrug, and its combination with topotecan in neuroblastoma and rhabdomyosarcoma preclinical models.
Experimental Design: Neuroblastoma and rhabdomyosarcoma cells were tested in vitro to assess the effect of evofosfamide on cell proliferation, both as a single agent and in combination with topotecan. In vivo antitumor activity was evaluated in different xenograft models. Animal survival was studied with the neuroblastoma metastatic tumor model.
Results: All tested cell lines showed response to evofosfamide under normoxic conditions, but when exposed to hypoxia overnight, a 2- to 65-fold decrease of IC50 was observed. Adding topotecan to the evofosfamide treatment significantly increased cytotoxicity in vitro. In neuroblastoma xenograft models, single-agent evofosfamide treatment delayed tumor growth. Complete tumor regression was observed in the combined topotecan/evofosfamide treatment group after 2-week treatment. Combined treatment also improved survival in a neuroblastoma metastatic model, compared to single-agent treatments. In rhabdomyosarcoma xenograft models, combined treatment was more effective than single agents. We also showed that evofosfamide mostly targeted tumor cells within hypoxic regions while topotecan was more effective to tumor cells in normoxic regions. Combined treatment induced tumor cell apoptosis in both normoxic and hypoxic regions.
Conclusions: Evofosfamide shows antitumor effects in neuroblastoma and rhabdomyosarcoma xenografts. Compared with single-agent, evofosfamide/topotecan, combined therapy improves tumor response, delays tumor relapse, and enhances animal survival in preclinical tumor models. Clin Cancer Res; 22(11); 2697–708. ©2015 AACR.
Translation Inhibition by Rocaglates Is Independent of eIF4E Phosphorylation Status
Authors: Chu Jennifer , Cencic Regina , Wang Wenyu , Porco John A. , Pelletier Jerry 
Published: December 2015

Abstract
Rocaglates are natural products that inhibit protein synthesis in eukaryotes and exhibit antineoplastic activity. In vitro biochemical assays, affinity chromatography experiments coupled with mass spectrometry analysis, and in vivo genetic screens have identified eukaryotic initiation factor (eIF) 4A as a direct molecular target of rocaglates. eIF4A is the RNA helicase subunit of eIF4F, a complex that mediates cap-dependent ribosome recruitment to mRNA templates. The eIF4F complex has been implicated in tumor initiation and maintenance through elevated levels or increased phosphorylation status of its cap-binding subunit, eIF4E, thus furthering the interest toward developing rocaglates as antineoplastic agents. Recent experiments have indicated that rocaglates also interact with prohibitins 1 and 2, proteins implicated in c-Raf-MEK-ERK signaling. Because increased ERK signaling stimulates eIF4E phosphorylation status, rocaglates are also expected to inhibit eIF4E phosphorylation status, a point that has not been thoroughly investigated. It is currently unknown whether the effects on translation observed with rocaglates are solely through eIF4A inhibition or also a feature of blocking eIF4E phosphorylation. Here, we show that rocaglates inhibit translation through an eIF4E phosphorylation–independent mechanism. Mol Cancer Ther; 15(1); 136–41. ©2015 AACR.
Human Leukocyte Antigen–Presented Macrophage Migration Inhibitory Factor Is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer
Authors: Patterson Andrea M. , Kaabinejadian Saghar , McMurtrey Curtis P. , Bardet Wilfried , Jackson Ken W. , Zuna Rosemary E. , Husain Sanam , Adams Gregory P. , MacDonald Glen , Dillon Rachelle L. , Ames Harold , Buchli Rico , Hawkins Oriana E. , Weidanz Jon A. , Hildebrand William H. 
Published: December 2015

Abstract
T cells recognize cancer cells via HLA/peptide complexes, and when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2–presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n = 27) and normal fallopian tube (n = 24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared with normal fallopian tube epithelium (P &lt; 0.0001), with minimal staining of normal stroma and blood vessels (P &lt; 0.0001 and P &lt; 0.001 compared with tumor cells) suggesting a therapeutic window. We then demonstrated the anticancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2–presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy. Mol Cancer Ther; 15(2); 313–22. ©2015 AACR.
A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition
Authors: Alagpulinsa David A. , Ayyadevara Srinivas , Yaccoby Shmuel , Shmookler Reis Robert J. 
Published: December 2015

Abstract
PARP1/2 are required for single-strand break repair, and their inhibition causes DNA replication fork collapse and double-strand break (DSB) formation. These DSBs are primarily repaired via homologous recombination (HR), a high-fidelity repair pathway. Should HR be deficient, DSBs may be repaired via error-prone nonhomologous end-joining mechanisms, or may persist, ultimately resulting in cell death. The combined disruption of PARP and HR activities thus produces synthetic lethality. Multiple myeloma cells are characterized by chromosomal instability and pervasive DNA damage, implicating aberrant DNA repair. Cyclin-dependent kinases (CDK), upstream modulators of HR, are dysregulated in multiple myeloma. Here, we show that a CDK inhibitor, dinaciclib, impairs HR repair and sensitizes multiple myeloma cells to the PARP1/2 inhibitor ABT-888. Dinaciclib abolishes ABT-888–induced BRCA1 and RAD51 foci and potentiates DNA damage, indicated by increased γH2AX foci. Dinaciclib treatment reduces expression of HR repair genes, including Rad51, and blocks BRCA1 phosphorylation, a modification required for HR repair, thus inhibiting HR repair of chromosome DSBs. Cotreatment with dinaciclib and ABT-888 in vitro resulted in synthetic lethality of multiple myeloma cells, but not normal CD19+ B cells, and slowed growth of multiple myeloma xenografts in SCID mice almost two-fold. These findings support combining dinaciclib with PARP inhibitors for multiple myeloma therapy. Mol Cancer Ther; 15(2); 241–50. ©2015 AACR.
Estimating Daytime Planetary Boundary Layer Heights over a Valley from Rawinsonde Observations at a Nearby Airport: An Application to the Page Valley in Virginia, United States
Authors: Lee Temple R. , De Wekker Stephan F. J. 
Published: December 2015

AbstractThe planetary boundary layer (PBL) height is an essential parameter required for many applications, including weather forecasting and dispersion modeling for air quality. Estimates of PBL height are not easily available and often come from twice-daily rawinsonde observations at airports, typically at 0000 and 1200 UTC. Questions often arise regarding the applicability of PBL heights retrieved from these twice-daily observations to surrounding locations. Obtaining this information requires knowledge of the spatial variability of PBL heights. This knowledge is particularly limited in regions with mountainous terrain. The goal of this study is to develop a method for estimating daytime PBL heights in the Page Valley, located in the Blue Ridge Mountains of Virginia. The approach includes using 1) rawinsonde observations from the nearest sounding station [Dulles Airport (IAD)], which is located 90 km northeast of the Page Valley, 2) North American Regional Reanalysis (NARR) output, and 3) simulations with the Weather Research and Forecasting (WRF) Model. When selecting days on which PBL heights from NARR compare well to PBL heights determined from the IAD soundings, it is found that PBL heights are higher (on the order of 200–400 m) over the Page Valley than at IAD and that these differences are typically larger in summer than in winter. WRF simulations indicate that larger sensible heat fluxes and terrain-following characteristics of PBL height both contribute to PBL heights being higher over the Page Valley than at IAD.
Dynamics of the ITCZ Boundary Layer
Authors: Gonzalez Alex O. , Slocum Christopher J. , Taft Richard K. , Schubert Wayne H. 
Published: December 2015

Abstract
This paper presents high-resolution numerical solutions of a nonlinear zonally symmetric slab model of the intertropical convergence zone (ITCZ) boundary layer. The boundary layer zonal and meridional flows are forced by a specified pressure field, which can also be interpreted as a specified geostrophically balanced zonal wind field ug(y). One narrow on-equatorial peak in boundary layer pumping is produced when the forcing is easterly geostrophic flow along the equator and two narrow peaks in boundary layer pumping are produced on opposite sides of the equator (a double ITCZ) when the forcing is westerly geostrophic flow along the equator. In the case when easterlies are surrounding a westerly wind burst, once again a double ITCZ is produced, but the ITCZs have significantly more intense boundary layer pumping than the case of only westerly geostrophic flow. A comparison of the numerical solutions to those of classical Ekman theory suggests that the meridional advection term υ(∂υ/∂y) plays a vital role in strengthening and narrowing boundary layer pumping regions while weakening and broadening boundary layer suction regions.
Temporal and Spatial Interpolation Errors of High-Resolution Modeled Atmospheric Fields
Authors: Privé N. C. , Errico R. M. 
Published: December 2015

AbstractGeneral circulation models can now be run at very high spatial resolutions to capture finescale features, but saving the full-spatial-resolution output at every model time step is usually not practical because of storage limitations. To reduce storage requirements, the model output may be produced at reduced temporal and/or spatial resolutions. When this reduced-resolution output is then used in situations where spatiotemporal interpolation is required, such as the generation of synthetic observations for observing system simulation experiments, interpolation errors can significantly affect the quality and usefulness of the reduced-resolution model output. Although it is common in practice to record model output at the highest possible spatial resolution with relatively infrequent temporal output, this may not be the best option to minimize interpolation errors. In this study, two examples using a high-resolution global run of the Goddard Earth Observing System Model, version 5 (GEOS-5), are presented to illustrate cases in which the optimal output dataset configurations for interpolation have high temporal frequency but reduced spatial resolutions. Interpolation errors of tropospheric temperature, specific humidity, and wind fields are investigated. The relationship between spatial and temporal output resolutions and interpolation errors is also characterized for the example model.
Evolution of Patients With Immediate Complete Facial Paralysis Secondary to Acoustic Neuroma Surgery
Authors: Pardo-Maza Adriana , Lassaletta Luis , González-Otero Teresa , Roda José María , Moraleda Susana , Arbizu Álvaro , Gavilán Javier 
Published: December 2015

Objective: To study the evolution of patients with immediate complete facial paralysis after acoustic neuroma surgery in different scenarios and assess different facial reanimations techniques. Methods: This study included 50 patients with complete facial paralysis immediately after acoustic neuroma surgery. Data were analyzed into 4 groups according to the need and type of reconstruction of the facial nerve, either none, immediate, or on a deferred basis. All patients had intraoperative facial nerve monitoring, and facial nerve function was evaluated according the House-Brackmann (HB) scale. Results: Of all patients with immediate total paralysis, no patients achieved totally normal facial function (grade I), and only 5 (10%) recovered to a grade II. For all groups included, the majority of patients (82%) achieved an acceptable final facial function (grade III HB). In this series, only 2 patients remained with a grade VI facial function. Conclusions: The possibility of recovering near normal facial function after a grade VI facial paralysis is very low. Procedures like the immediate repair of the facial nerve with an interposed donor graft may provide better facial function in patients with partially injured facial nerve. Even in cases of total section, there are other procedures that can improve the results.
Can renaming schizophrenia reduce negative attitudes toward patients in Turkey?
Authors: Aker Servet , Böke Ömer , Oğuz Gülay 
Published: December 2015

Aim: To determine the perception of the term schizophrenia among university students. Methods: This cross-sectional study was performed in April 2015 with students from Canik Başarı University (Samsun/Turkey). A patient history was first established. We then investigated to what extent students agreed with 10 statements based on that patient history. Three separate questionnaire forms (versions A, B and C), differing only in terms of the diagnosis in the patient in the history, were prepared. The three diagnoses were ‘Schizophrenia’ (version A), ‘A psychiatric disease by the name of Bleuler’s syndrome’ (version B) and ‘Brain tumor’ (version C). The questionnaires were administered in a class environment. In all, 771 students participated. Results: Statistically significant differences between the forms were determined in only two statements (‘A.’s disease will represent a problem in A.’s future career’ and ‘A. will in all probability have problems with the law in the future’). While no difference was determined between versions A and B at two-way comparisons, a statistically significant difference was observed between versions A and B and version C. Conclusion: No difference was determined between students’ attitudes toward a diagnosis of ‘schizophrenia’ and one of ‘a psychiatric disease known as Bleuler’s syndrome’. The focus in preventing stigmatization of schizophrenia should not concentrate on a name change alone. Changing the name schizophrenia may be of no use unless public ignorance and fear of psychiatric diseases can also be overcome.
Ultrasound-Guided Versus Blind Subacromial Corticosteroid Injections for Subacromial Impingement Syndrome
Authors: Cole Brandi F. , Peters Karin S. , Hackett Lisa , Murrell George A.C. 
Published: December 2015

Background: Subacromial corticosteroid injections are frequently performed for impingement syndrome of the shoulder. To improve the accuracy of injections, ultrasound can be used. Purpose: To assess the clinical outcome of ultrasound-guided subacromial injections compared with blind subacromial injections for subacromial impingement syndrome. Study Design: Randomized controlled clinical trial; Level of evidence, 1. Methods: A total of 56 shoulders with subacromial impingement syndrome were randomized into 2 groups: 28 shoulders received a subacromial corticosteroid injection with ultrasound guidance (ultrasound group), and 28 shoulders received a subacromial corticosteroid injection without ultrasound guidance (blind group). The visual analog scale (VAS) for pain with overhead activities and the American Shoulder and Elbow Surgeons (ASES) score were obtained before the injection and at 6 weeks after the injection. Results: The VAS score for pain with overhead activities decreased from 59 ± 5 mm (mean ± SEM) before the injection to 33 ± 6 mm at 6 weeks after the injection in the ultrasound group ( P < .001) and from 63 ± 4 mm to 39 ± 6 mm, respectively, in the blind group ( P < .001). The decrease in the VAS score was not significantly different between the groups ( P > .999). The ASES score increased from 57 ± 2 before the injection to 68 ± 3 at 6 weeks after the injection in the ultrasound group ( P < .01) and from 54 ± 3 before the injection to 65 ± 4 after the injection in the blind group ( P < .01), with no significant difference between the groups ( P = .7). Four shoulders (14%) in the ultrasound group and 6 shoulders (21%) in the blind group eventually needed surgery ( P = .7). Conclusion: No significant differences were found in the clinical outcome when comparing ultrasound-guided subacromial injections to blind subacromial injections for subacromial impingement syndrome. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12615000562572
Osteochondral Allograft Transplantation of the Femoral Trochlea
Authors: Cameron James I. , Pulido Pamela A. , McCauley Julie C. , Bugbee William D. 
Published: December 2015

Background: Osteochondral allograft (OCA) transplantation is a recognized treatment modality for cartilage damage in the knee. Few reports are available on outcomes of OCA in the patellofemoral joint, and there are no reports on lesions isolated to the femoral trochlea. Purpose: To evaluate graft survivorship and clinical outcomes in patients who had an OCA to the femoral trochlea. Study Design: Case series; Level of evidence, 4. Methods: An OCA database was used to identify 29 knees in 28 patients (mean age, 30.2 years; range, 12-47 years; 8 female, 20 male) who were treated with a fresh OCA transplant limited to the femoral trochlea. The primary outcome was graft survivorship, and the minimum follow-up was 2 years. Clinical outcomes were assessed by the modified Merle d’Aubigné-Postel (18-point) score; Knee Society function (KS-F) score; International Knee Documentation Committee (IKDC) pain, function, and total scores; and University of California, Los Angeles (UCLA) activity score. The OCA patient satisfaction score (5-point scale from extremely satisfied to dissatisfied) was also reported. Results: The mean follow-up period was 7.0 years (range, 2.1-19.9 years). Graft survivorship was 100% at 5 years and 91.7% at 10 years. One patient was converted to a total knee arthroplasty 7.6 years after OCA surgery. The mean modified Merle d’Aubigné-Postel score improved from 13.0 to 16.1, the mean KS-F score from 65.6 to 85.2, and the mean IKDC total score from 38.5 to 71.9; the mean UCLA score was 7.9 postoperatively. Eighty-nine percent of patients were extremely satisfied or satisfied with the outcome of surgery. Conclusion: Fresh OCA transplantation resulted in excellent clinical outcomes in this patient cohort with articular cartilage damage to the femoral trochlea. The procedure resulted in improved pain and function and high patient satisfaction.
Biomechanical Comparison of Ulnar Collateral Ligament Repair With Internal Bracing Versus Modified Jobe Reconstruction
Authors: Dugas Jeffrey R. , Walters Brian L. , Beason David P. , Fleisig Glenn S. , Chronister Justin E. 
Published: December 2015

Background: The number of throwing athletes with ulnar collateral ligament (UCL) injuries has increased recently, with a seemingly exponential increase of such injuries in adolescents. In cases of acute proximal or distal UCL insertion injuries or in partial-thickness injuries that do not respond to nonoperative management, UCL repair and augmentation rather than reconstruction may be a viable option. Purpose/Hypothesis: The purpose of this study was to biomechanically compare a new technique of augmented UCL repair versus a typical modified Jobe UCL reconstruction technique. The hypotheses were that (1) the repaired specimens would have less gap formation and a higher maximal torque to failure compared with the reconstruction group, and (2) while both groups would show an increase in gap formation after the simulated tear, the repair group would return closer to the native values compared with the reconstruction group. Study Design: Controlled laboratory study. Methods: Nine matched pairs of cadaveric arms were dissected to expose the UCL. Each elbow was mounted on a test frame at 90° of flexion. A cyclic valgus rotational torque was applied to the humerus with the UCL in its intact state and repeated in its surgically torn state. Finally, each specimen received either an augmented repair or reconstruction and was again put through the cyclic protocol, followed by a torque to failure. Results: Gap formation (0.51 ± 0.22 mm) in the torn state for the repair group was significantly higher ( P = .04) than in the intact state (0.33 ± 0.12 mm). After the procedures, the repair group (0.35 ± 0.16 mm) showed greater resistance to gapping ( P = .03) compared with the reconstruction group (0.53 ± 0.23 mm). No statistical differences were found for the maximum torque at failure, torsional stiffness, or gap formation during the failure test. Conclusion: The current study shows that this novel technique of augmented UCL repair replicates the time-zero failure strength of traditional graft reconstruction and appears to be more resistant to gapping at low cyclic loads. Clinical Relevance: This study demonstrates that this novel technique has important biomechanical properties, including time-zero strength and ultimate failure load, compared with the gold standard of UCL reconstruction. In some throwing athletes, this technique may supplant standard UCL reconstruction as the procedure of choice.