bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Study of Continuous Oral Dosing of OSI-906, a Dual Inhibitor of Insulin-Like Growth Factor-1 and Insulin Receptors, in Patients with Advanced Solid Tumors
Authors: Puzanov Igor , Lindsay Colin R. , Goff Laura , Sosman Jeff , Gilbert Jill , Berlin Jordan , Poondru Srinivasu , Simantov Ronit , Gedrich Rich , Stephens Andrew , Chan Emily , Evans T.R. Jeffry 
Published: September 2014

Abstract
Purpose: OSI-906 is a potent inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR). The purpose of this study was to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906 in patients with advanced solid tumors.
Patients and Methods: This was a nonrandomized, open-label, phase I, dose-escalation study in patients with advanced solid tumors. The study also included a diabetic expansion cohort and a biomarker expansion cohort of patients with colorectal cancer. Patients were treated with OSI-906 by once- or twice-daily continuous dosing schedules.
Results: Of 95 patients enrolled in the study, 86 received at least one dose of OSI-906. Dose-limiting toxicities included QTc prolongation, grade 2 abdominal pain and nausea, hyperglycemia, and elevation of aspartate aminotransferase and alanine aminotransferase (all grade 3). The MTDs were established to be 400 mg once daily and 150 mg twice daily. The recommended phase II dose was determined as 150 mg twice daily. OSI-906 was rapidly absorbed with a half-life of 5 hours, and steady-state plasma concentrations were achieved by day 8. Pharmacodynamic effects on IGF1R and IR phosphorylation were levels observed and correlated with plasma concentrations of OSI-906. Thirty-one patients had stable disease as their best response. One patient with melanoma had a radiographic partial response and underwent resection, during which only melanocytic debris but no viable tumor tissue was identified.
Conclusions: At the established MTD, OSI-906 was well tolerated and antitumor activity was observed. These results support further evaluation of OSI-906 in solid tumors. Clin Cancer Res; 21(4); 701–11. ©2014 AACR.
See related commentary by Yee, p. 667
Effect of Phosphodiesterase Inhibition on Insulin Resistance in Obese Individuals
Authors: Ho Jennifer E. , Arora Pankaj , Walford Geoffrey A. , Ghorbani Anahita , Guanaga Derek P. , Dhakal Bishnu P. , Nathan Daniel I. , Buys Emmanuel S. , Florez Jose C. , Newton‐Cheh Christopher , Lewis Gregory D. , Wang Thomas J. 
Published: September 2014

Background

Obesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate (
cGMP
) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase‐5 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals.

Methods and Results

We conducted a randomized, double‐blinded, placebo‐controlled trial of adults age 18 to 50 years with obesity and elevated fasting insulin levels (≥10 μU/
mL
). Participants were randomized to tadalafil 20 mg daily or placebo for 3 months. Oral glucose tolerance tests were performed, and the effect of tadalafil on IR was examined. A total of 53 participants (mean age, 33 years; body mass index [BMI], 38 kg/m
2
) were analyzed, 25 randomized to tadalafil and 28 to placebo. In the overall sample, measures of IR did not differ between tadalafil and placebo groups at 3 months. However, in individuals with severe obesity (BMI ≥36.2 kg/m
2
), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo (
P
=0.02, respectively). Furthermore, one measure of β‐cell compensation for IR (oral disposition index) improved with tadalafil in the overall sample (
P
=0.009) and in the subgroup with severe obesity (
P
=0.01).

Conclusion

Results of this pilot study did not show improvements in IR with tadalafil, compared to placebo. However, tadalafil may have favorable effects on β‐cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of
cGMP
modulation in obesity are warranted.

Clinical Trial Registration
URL: ClinicalTrials.gov. Unique Identifier: NCT01444651.
Hip Range of Motion and Association With Injury in Female Professional Tennis Players
Authors: Young Simon W. , Dakic Jodie , Stroia Kathleen , Nguyen Michael L. , Harris Alex H.S. , Safran Marc R. 
Published: September 2014

Background: Adequate hip range of motion is required for the transfer of energy from the lower to the upper extremity along the kinetic chain. Repetitive rotational stresses in the lower extremities during tennis may lead to sport-specific range of motion adaptations, which may increase the risk of injury to other joints along the kinetic chain. Purpose: To assess whether such range of motion adaptations occur in the hip, and if so, to identify whether they are associated with injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 125 female professional tennis players, the majority of whom were ranked in the top 200 World Tennis Association singles rankings, underwent a comprehensive preparticipation physical health status examination. Hip range of motion was assessed using a digital inclinometer and side-to-side differences in rotational parameters calculated, and associations with previous injuries were identified. Results: A history of an abdominal strain was reported by 10% of players, and there was an association between abdominal strains and the presence of hip flexion contractures (odds ratio, 6.1; P = .006). Hip flexion contractures were bilateral in 85% of those found, affected only the nondominant side in 9%, and affected only the dominant side in 6%. We were unable to identify any specific side-to-side rotational adaptations in the dominant or nondominant hips, and no association between loss of hip range of motion and shoulder, lower back, hip, knee, or ankle injuries was found. Conclusion: We report an association in female professional tennis players between abdominal strains and flexion contractures of the hip with iliopsoas tightness. We did not find evidence of specific hip adaptations in rotational range of motion. If hip flexion contractures are found on clinical examination, a stretching program may be indicated. Further studies are required to assess whether such a program can reduce the risk of abdominal injury.
Effect of Posterior Tibial Tendon Dysfunction on Unipedal Standing Balance Test
Authors: Kulig Kornelia , Lee Szu-Ping , Reischl Stephen F. , Noceti-DeWit Lisa 
Published: September 2014

Background: Foot pain and diminished functional capacity are characteristics of tibialis posterior tendon dysfunction (TPTD). This study tested the hypotheses that women with TPTD would have impaired performance of a unipedal standing balance test (USBT) and that balance performance would be related to the number of single limb heel raises (SLHR). Methods: Thirty-nine middle-aged women, 19 with early stage TPTD (stage I and II), were instructed to perform 2 tasks; a USBT and repeated SLHR. Balance success was defined as a 10-second stance. For those who were successful, center of pressure (COP) data in anterior-posterior (AP) and medial-lateral (ML) directions were recorded as a measure of postural sway. SLHR performance was divided into 3 bins (≤2; 3-9 and > 10 repetitions). The between-balance success on performing the SLHR test was analyzed using the Fisher’s exact test (2 × 3). Independent t tests were used to compare between-group differences in postural sway. Relationship of postural sway to the number of heel raises was assessed using Spearman’s rho. Results: The success rate of the USBT was significantly lower in women with TPTD than the controls (47% vs 85%, P = .041). In addition, women with TPTD who completed the USBT exhibited increased AP COP displacement (14.0 ± 7.4 vs 8.4 ± 1.3 mm, P = .008), and a strong trend of increased ML COP displacement (8.3 ± 4.5 vs 6.1 ± 1.2 mm, P = .050). The success rate of USBT was correlated with the number of SLHR ( P = .01). The AP and ML COP displacement were correlated with SLHR ( r = −.538 and .495), respectively. Conclusions: Women with TPTD have difficulty in performing the USBT. Performance of the USBT and SLHR are highly correlated and predictive of each other. Clinical Relevance: A unipedal balance test may be used as a proxy TPTD assessment tool to the heel raising test when pain prevents performance. Level of Evidence: Level III, case control study.
Association between market concentration of hospitals and patient health gain following hip replacement surgery
Authors: Feng Yan , Pistollato Michele , Charlesworth Anita , Devlin Nancy , Propper Carol , Sussex Jon 
Published: September 2014

Objectives To assess the association between market concentration of hospitals (as a proxy for competition) and patient-reported health gains after elective primary hip replacement surgery. Methods Patient Reported Outcome Measures data linked to NHS Hospital Episode Statistics in England in 2011/12 were used to analyse the association between market concentration of hospitals measured by the Herfindahl-Hirschman Index (HHI) and health gains for 337 hospitals. Results The association between market concentration and patient gain in health status measured by the change in Oxford Hip Score (OHS) after primary hip replacement surgery was not statistically significant at the 5% level both for the average patient and for those with more than average severity of hip disease (OHS worse than average). For 12,583 (49.1%) patients with an OHS before hip replacement surgery better than the mean, a one standard deviation increase in the HHI, equivalent to a reduction of about one hospital in the local market, was associated with a 0.104 decrease in patients’ self-reported improvement in OHS after surgery, but this was not statistically significant at the 5% level. Conclusions Hospital market concentration (as a proxy for competition) appears to have no significant influence (at the 5% level) on the outcome of elective primary hip replacement. The generalizability of this finding needs to be investigated.
Gastro‐oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH‐impedance and endoscopic study
Authors: Wilder-Smith Clive H , Materna Andrea , Martig Lukas , Lussi Adrian 
Published: September 2014

BackgroundDental erosion is a complication of gastro‐oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH‐impedance measures have not been reported.ObjectivesCharacterize GORD in patients with dental erosions using 24‐h multichannel intraluminal pH‐impedance measurements (pH‐MII) and endoscopy.MethodsThis single‐centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH‐MII and endoscopy.ResultsOf the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH‐MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3–12.7), and 34.4% (31.9–36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63–79), 43 (38–49) and 31 (26–35), respectively. Of the reflux episodes, 19% (17–21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores.ConclusionsSignificant oligosymptomatic gastro‐oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH‐MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD.
Temperature dependence of sensitized Er3+ luminescence in silicon-rich oxynitride films
Authors: Xu Lingbo , Li Si , Jin Lu , Li Dongsheng , Yang Deren 
Published: September 2014

Abstract
The temperature dependence of sensitized Er3+ emission via localized states and silicon nanoclusters has been studied to get an insight into the excitation and de-excitation processes in silicon-rich oxynitride films. The thermal quenching of Er3+ luminescence is elucidated by terms of decay time and effective excitation cross section. The temperature quenching of Er3+ decay time demonstrates the presence of non-radiative trap states, whose density and energy gap between Er3+
4
I
13/2 excited levels are reduced by high-temperature annealing. The effective excitation cross section initially increases and eventually decreases with temperature, indicating that the energy transfer process is phonon assisted in both samples.
Anatomical and physiological studies of bigheaded carps demonstrate that the epibranchial organ functions as a pharyngeal taste organ
Authors: Hansen Anne , Ghosal Ratna , Caprio John , Claus Aaron , Sorensen Peter 
Published: September 2014

Abstract
The epibranchial organ (EO) is an enigmatic tubular organ found in the pharyngeal cavity of many filter-feeding fishes. We investigated whether it might function as a taste organ that mediates aggregation and ingestion of planktonic food. The EO and associated structures of bighead and silver carps, two successful and invasive planktivorous fishes, were examined using histological and electrophysiological techniques. Both species possess finely structured gill rakers that extend directly via a series of protrusions into each of the four blind canals which are organized as the muscular EO suggesting that the gill rakers and EO likely function in an integrated manner. Both the interior and exterior surfaces of the EOs of both species are covered with high densities of taste buds and solitary chemosensory cells (SCCs) as well as mucous cells. Conversely, taste buds are scarce in both the buccal cavities and external portions of the head and mouth of both species. Electrophysiological recordings from a caudal branch of the vagus nerve (cranial nerve X) found to innervate the EO showed it to be sensitive to chemicals found in a planktonic diet. L-Amino acids accounted for some, but not all of the neural activity. We conclude that taste buds and SCCs located on the EO and gill rakers likely serve to chemically detect food particles, which the EO then aggregates by mucus secretion before eventually expelling them onto the floor of the pharynx for ingestion. This specialized, pharyngeal chemosensory structure may explain the feeding success of these, and perhaps other planktivorous, filter-feeding fishes.
The Gospel and the Golden Age of the Russian Literature
Authors: Щелкунова  , Shchelkunova Svetlana 
Published: September 2014

The selective course outline “The Gospel and the Golden Age of the Russian Literature” is aimed at 10th and 11th-class students of humanitarian-profile
classes. The elective course content will acquaint students with the broad-wide culturological and historian and literature context, anв will introduce the
idea of studying the classical Russian literature through the prism of gospel stories and proverbs.
Mission and Sustainability of Informatics for Integrating Biology and the Bedside
(i2b2)
Authors: Murphy Shawn N. , Wilcox Adam 
Published: September 2014

Introduction: A visible example of a successfully disseminated research project in
the healthcare space is Informatics for Integrating Biology and the Bedside, or i2b2.
The project serves to provide the software that can allow a researcher to do direct,
self-serve queries against the electronic healthcare data form a hospital. The goals of
these queries are to find cohorts of patients that fit specific profiles, while
providing for patient privacy and discretion. Sustaining this resource and keeping its
direction has always been a challenge, but ever more so as the ten year National Centers
for Biomedical Computing (NCBCs) sunset their funding.Findings: Building on the i2b2
structures has helped the dissemination plans for grants leveraging it because it is a
disseminated national resource. While this has not directly increased the support of
i2b2 internally, it has increased the ability of institutions to leverage the resource
and generally leads to increased institutional support.Discussion: The successful
development, use, and dissemination i2b2 has been significant in clinical research and
informat­ics. Its evolution has been from a local research data infrastruc­ture to one
disseminated more broadly than any other product of the National Cen­ters for Biomedical
Computing, and an infrastructure spawning larger investments than were originally used
to create it. Throughout this, there were two main lessons about the benefits of
dissemination: that people have great creativity in utilizing a resource in different
ways and that broader system use can make the system more robust. One option for
long-term sustainability of the central authority would be to translate the function to
an industry partner. Another option currently being pursued is to create a foundation
that would be a central authority for the project.Conclusion: Over the past 10 years,
i2b2 has risen to be an important staple in the toolkit of health care researchers.
There are now over 110 hospitals that use i2b2 for research. This open-source platform
has a community of developers that are continuously enhancing the analytic capacities of
the platform and inventing new func­tionality. By understanding how i2b2 has been
sustained, we hope that other research infrastructure projects may better navigate
options in making those initiatives sustainable over time.
Strain hardening exponents and strength coefficients for aeroengine isotropic metallic materials – a reverse engineering approach
Authors: Rajendran R. , Venkateshwarlu M. , Petley Vijay , Verma Shweta 
Published: September 2014

AbstractThe strain hardening exponent and strength coefficient of the Ramberg-Osgood flow rule are required for the accurate design analysis of the materials of aeroengine components. A direct method of deriving these parameters involves the processing of the complete raw data of tensile testing as per ASTM E-646. More often, a first design effort of aeroengine components is made using catalogue data, as the evaluation of material tensile properties is a time-consuming process that takes place concurrently. Catalogue-supplied data on the monotonic loading typically contains elastic modulus, 0.2% proof stress, and ultimate tensile stress along with other data for various temperatures. A methodology was evolved in this work to construct the Ramberg-Osgood flow rule with these three parameters and was validated with laboratory test results and published data through a comparison with ASTM E-646. The strain hardening exponents and strength coefficients were established for a family of aeroengine metallic materials for various temperatures, which can serve as a first design effort input.
Selection of stabilizing agents to provide effective penetration of gold nanoparticles into cells
Authors: Elagin Vadim V. , Sergeeva Ekaterina A. , Bugrova Marina L. , Ignatova Nadezhda I. , Yuzhakova Diana V. , Denisov Nikolay N. , Nadtochenko Victor A. , Zagaynova Elena V. 
Published: September 2014

AbstractObjective:Gold nanorods are known to be promising agents for photothermal therapy. But the uptake of rod-shaped nanoparticles is lower than their spherical counterpart. It was therefore the objective of this study to select gold nanoparticles (GNPs)-stabilizing agents in order to provide effective penetration into cancer cells.Materials and methods:The work was carried out on human ovarian adenocarcinoma SKOV-3 cells. The gold nanorods used in this work had a plasmon resonance peak at 800 nm. The nanoparticles were stabilized by PluronicResults:By means of 2PLM and TEM, it could be shown that PF127 facilitates cellular uptake of GNPs very effectively. PF127-stabilized GNPs rapidly (by 1.5 h) penetrated the cell membrane and into the cytoplasm and cell nucleus. GNPs stabilized by chitosan were slowly internalized by the cells in smaller amount. GNPs stabilized by PEG with different molecular weights had difficulty to penetrate into the cells – GNPs were localized on the outer side of the cell membrane after short incubation, and single agglomerates were found in the cells after an extended incubation time.Conclusion:Nanoparticles stabilized with PF127 were the most effective nanoparticles to penetrate into the cells and were located in the cytoplasm and cell nuclei. Nanoparticles stabilized with chitosan were internalized into cells at a slower rate and in smaller amounts than those stabilized with PF127. Nanoparticles stabilized with PEG
Nucleate Boiling Heat Transfer: Temperature Pulsations or Local Thermal Shocks
Authors: Shekriladze Irakli G. 
Published: September 2014

Abstract
This paper discusses thermo-mechanical consequences of the pumping effect of growing bubble (PEGB) resulting in surface thermal stresses during nucleate boiling. Unfortunately, the unavailability of boiling heat transfer studies specifically addressing the scope and duration of the PEGB effect, including lack of models and universal correlations of boiling heat transfer, has hindered the overall understanding of nucleate boiling heat transfer to date. As a result, specific types of cyclic thermal stresses at the surface which are capable of producing thermal shocks in some boiling regimes and that are attributable to PECB have remained unexplored. This has prevented complete theoretical determination of the service life of heating surfaces of boiling systems such as boiling water reactors (BWR) and metal quenching technology. In this paper, some preliminary estimates of the tasks required for experimental studies required for further theoretical development are presented. With regard to the quenching processes, discussions regarding the probable negligible consequences of thermal stresses caused by the PEGB are presented.
Regulation of Mitotic Spindle Disassembly by an Environmental Stress-Sensing Pathway in Budding Yeast
Authors: Pigula Adrianne , Drubin David G , Barnes Georjana 
Published: September 2014

AbstractTimely spindle disassembly is essential for coordination of mitotic exit with cytokinesis. In the budding yeast Saccharomyces cerevisiae, the microtubule-associated protein She1 functions in one of at least three parallel pathways that promote spindle disassembly. She1 phosphorylation by the Aurora kinase Ipl1 facilitates a role for She1 in late anaphase, when She1 contributes to microtubule depolymerization and shrinkage of spindle halves. By examining the genetic interactions of known spindle disassembly genes, we identified three genes in the environmental stress-sensing HOG (high-osmolarity glycerol response) pathway, SHO1, PBS2, and HOG1, and found they are necessary for proper localization of She1 to the anaphase spindle and for proper spindle disassembly. HOG pathway mutants exhibited spindle disassembly defects, as well as mislocalization of anillin-related proteins Boi1 and Boi2 from the bud neck. Moreover, Boi2, but not Boi1, plays a role in spindle disassembly that places Boi2 in a pathway with Sho1, Pbs2, and Hog1. Together, our data identify a process by which cells monitor events at the spindle and bud neck and describe a novel role for the HOG pathway in mitotic signaling.