bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Clinical Trial and Independent Patient-Derived Xenograft Study of Combined Targeted Treatment with Dacomitinib and Figitumumab in Advanced Solid Tumors
Authors: Calvo Emiliano , Soria Jean-Charles , Ma Wen Wee , Wang Tao , Bahleda Rastilav , Tolcher Anthony W. , Gernhardt Diana , O'Connell Joseph , Millham Robert , Giri Nagdeep , Wick Michael J. , Adjei Alex A. , Hidalgo Manuel 
Published: October 2016

Abstract
Purpose: This phase I, open-label, single-arm trial assessed the safety and tolerability of dacomitinib–figitumumab combination therapy in patients with advanced solid tumors.
Experimental Design: A standard 3 + 3 dose escalation/de-escalation design was utilized. Starting doses were figitumumab 20 mg/kg administered intravenously once every 3 weeks and dacomitinib 30 mg administered orally once daily. We also performed an independent study of the combination in patient-derived xenograft (avatar mouse) models of adenoid cystic carcinoma.
Results: Of the 74 patients enrolled, the most common malignancies were non–small cell lung cancer (24.3%) and colorectal cancer (14.9%). The most common treatment-related adverse events in the 71 patients who received treatment across five dose levels were diarrhea (59.2%), mucosal inflammation (47.9%), and fatigue and acneiform dermatitis (45.1% each). The most common dose-limiting toxicity was mucosal inflammation. Dosing schedules of dacomitinib 10 or 15 mg daily plus figitumumab 20 mg/kg every 3 weeks after a figitumumab loading dose were tolerated by patients over multiple cycles and considered recommended doses for further evaluation. Objective responses were seen in patients with adenoid cystic carcinoma, ovarian carcinoma, and salivary gland cancer. Pharmacokinetic analysis did not show any significant drug−drug interaction. In the adenoid cystic carcinoma xenograft model, figitumumab exerted significant antitumor activity, whereas dacomitinib did not. Figitumumab-sensitive tumors showed downregulation of genes in the insulin-like growth factor receptor 1 pathway.
Conclusions: Dacomitinib−figitumumab combination therapy was tolerable with significant dose reductions of both agents to less than the recommended single-agent phase II dose of each drug. Preliminary clinical activity was demonstrated in the potential target tumor adenoid cystic carcinoma. Clin Cancer Res; 23(5); 1177–85. ©2016 AACR.
See related commentary by Sundar et al., p. 1123
Mechanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue
Authors: Ruan Jia-Ling , Tulloch Nathaniel L. , Razumova Maria V. , Saiget Mark , Muskheli Veronica , Pabon Lil , Reinecke Hans , Regnier Michael , Murry Charles E. 
Published: October 2016

Background:
Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues.

Methods:
Cardiomyocytes derived from human-induced pluripotent stem cells were used to generate collagen-based bioengineered human cardiac tissue. Engineered tissue constructs were subjected to different mechanical stress and electric pacing conditions.

Results:

The engineered human myocardium exhibits Frank-Starling–type force-length relationships. After 2 weeks of static stress conditioning, the engineered myocardium demonstrated increases in contractility (0.63±0.10 mN/mm
2
vs 0.055±0.009 mN/mm
2
for no stress), tensile stiffness, construct alignment, and cell size. Stress conditioning also increased SERCA2 (Sarco/Endoplasmic Reticulum Calcium ATPase 2) expression, which correlated with a less negative force-frequency relationship. When electric pacing was combined with static stress conditioning, the tissues showed an additional increase in force production (1.34±0.19 mN/mm
2
), with no change in construct alignment or cell size, suggesting maturation of excitation-contraction coupling. Supporting this notion, we found expression of RYR2 (Ryanodine Receptor 2) and SERCA2 further increased by combined static stress and electric stimulation.

Conclusions:
These studies demonstrate that electric pacing and mechanical stimulation promote maturation of the structural, mechanical, and force generation properties of human-induced pluripotent stem cell-derived cardiac tissues.
Relationships between labile soil organic matter and nematode communities in a California oak woodland
Authors: Margenot Andrew J. , Hodson Amanda K. 
Published: October 2016

Labile soil organic matter (SOM) is an important energy source for below-ground ecosystems but the association of labile SOM and nematode communities is poorly characterised. In this study, soil nematode communities and nematode-derived indices of ecosystem function were characterised and related to SOM lability in an undisturbed riparian woodland (California, USA). SOM lability was assessed by microbial biomass C (MBC), permanganate-oxidisable C (POXC), extractable organic C (EOC), and diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. The channel index, which measures the ratio of bacterial-feeding to fungal-feeding nematodes in cp groups 1 and 2, respectively, decreased with labile C fractions and aliphatic C-H enrichment (infrared absorbance at 2920 cm−1) but increased with aromatic C=C enrichment (1620 cm−1) and index of decomposition (2930:1620 cm−1), as did the nematode structure index. These results indicate that nematode communities respond to variation in labile C fractions and SOM composition across a heterogeneous natural landscape, which may reflect observed differences in SOM lability among woody plant species.
Earth System Science Frontiers: An Early Career Perspective
Authors: Rauser Florian , Alqadi Mohammad , Arowolo Steve , Baker Noël , Bedard Joel , Behrens Erik , Dogulu Nilay , Domingues Lucas Gatti , Frassoni Ariane , Keller Julia , Kirkpatrick Sarah , Langendijk Gaby , Mirsafa Masoumeh , Mohammad Salauddin , Naumann Ann Kristin , Osman Marisol , Reed Kevin , Rothmüller Marion , Schemann Vera , Singh Awnesh , Sonntag Sebastian , Tummon Fiona , Victor Dike , Villafuerte Marcelino Q. , Walawender Jakub P. , Zaroug Modathir 
Published: October 2016

Abstract
The exigencies of the global community toward Earth system science will increase in the future as the human population, economies, and the human footprint on the planet continue to grow. This growth, combined with intensifying urbanization, will inevitably exert increasing pressure on all ecosystem services. A unified interdisciplinary approach to Earth system science is required that can address this challenge, integrate technical demands and long-term visions, and reconcile user demands with scientific feasibility. Together with the research arms of the World Meteorological Organization, the Young Earth System Scientists community has gathered early-career scientists from around the world to initiate a discussion about frontiers of Earth system science. To provide optimal information for society, Earth system science has to provide a comprehensive understanding of the physical processes that drive the Earth system and anthropogenic influences. This understanding will be reflected in seamless prediction systems for environmental processes that are robust and instructive to local users on all scales. Such prediction systems require improved physical process understanding, more high-resolution global observations, and advanced modeling capability, as well as high-performance computing on unprecedented scales. At the same time, the robustness and usability of such prediction systems also depend on deepening our understanding of the entire Earth system and improved communication between end users and researchers. Earth system science is the fundamental baseline for understanding the Earth’s capacity to accommodate humanity, and it provides a means to have a rational discussion about the consequences and limits of anthropogenic influence on Earth. Without its progress, truly sustainable development will be impossible.
Observed Changes in the Southern Hemispheric Circulation in May
Authors: Ivy Diane J. , Hilgenbrink Casey , Kinnison Doug , Alan Plumb R. , Sheshadri Aditi , Solomon Susan , Thompson David W. J. 
Published: October 2016

AbstractMuch research has focused on trends in the Southern Hemispheric circulation in austral summer (December–February) in the troposphere and stratosphere, whereas changes in other seasons have received less attention. Here the seasonality and structure of observed changes in tropospheric and stratospheric winds, temperature, and ozone over the Southern Hemisphere are examined. It is found that statistically significant trends similar to those of the Antarctic summer season are also observed since 1979 in austral fall, particularly May, and are strongest over the Pacific sector of the hemisphere. Evidence is provided for a significant shift in the position of the jet in May over the Pacific, and it is shown that the strengthening and shifting of the jet has rendered the latitudinal distribution of upper-tropospheric zonal wind more bimodal. The Antarctic ozone hole has cooled the lower stratosphere and strengthened the polar vortex. While the mechanism and timing are not fully understood, the ozone hole has been identified as a key driver of the summer season tropospheric circulation changes in several previous observational and modeling studies. It is found here that significant ozone depletion and associated polar cooling also occur in the lowermost stratosphere and tropopause region through austral fall, with spatial patterns that are coincident with the observed changes in stratospheric circulation. It is also shown that radiatively driven temperature changes associated with the observed ozone depletion in May represent a substantial portion of the observed May cooling in the lowermost stratosphere, suggesting a potential for contribution to the circulation changes.
Assessing Adaptation Strategies for Extreme Heat: A Public Health Evaluation of Cooling Centers in Maricopa County, Arizona
Authors: Berisha Vjollca , Hondula David , Roach Matthew , White Jessica R. , McKinney Benita , Bentz Darcie , Mohamed Ahmed , Uebelherr Joshua , Goodin Kate 
Published: October 2016

Abstract
Preventing heat-associated morbidity and mortality is a public health priority in Maricopa County, Arizona (United States). The objective of this project was to evaluate Maricopa County cooling centers and gain insight into their capacity to provide relief for the public during extreme heat events. During the summer of 2014, 53 cooling centers were evaluated to assess facility and visitor characteristics. Maricopa County staff collected data by directly observing daily operations and by surveying managers and visitors. The cooling centers in Maricopa County were often housed within community, senior, or religious centers, which offered various services for at least 1500 individuals daily. Many visitors were unemployed and/or homeless. Many learned about a cooling center by word of mouth or by having seen the cooling center’s location. The cooling centers provide a valuable service and reach some of the region’s most vulnerable populations. This project is among the first to systematically evaluate cooling centers from a public health perspective and provides helpful insight to community leaders who are implementing or improving their own network of cooling centers.
Student-led health education programmes in the waiting room of a free clinic for uninsured patients
Authors: Kamimura Akiko , Tabler Jennifer , Myers Kyl , Ahmed Fattima , Aguilera Guadalupe , Ashby Jeanie 
Published: October 2016

Objective: Free clinics provide free or reduced fee healthcare to individuals who lack access to primary care and are socio-economically disadvantaged in the USA. Free clinic patients may have health education needs, but experience barriers to attending health education programmes. In an attempt to reach out to free clinic patients who might not otherwise attend health education classes, this project examined the efficacy of student-led health education classes conducted in the waiting room prior to a patient’s appointment with a provider. Design: The classes had two areas of focus: women’s health and health information. Health educators and Spanish interpreters were graduate and undergraduate students. Setting: This study was conducted in the waiting room of a free clinic in the Intermountain West region of the USA. Method: The health education classes were held 22 times in total from late August to early December 2014. Results: While the survey-based assessment of the programme did not show a difference in levels of health consciousness, health information seeking and health attitudes, the programme potentially increased interest in attending the health education classes. Conclusion: There were some challenges associated with the implementation of a health education class in the waiting room setting, particularly in regards to environments, evaluation and interpretation services. Future projects are needed to address challenges associated with conducting a health education class in a waiting room setting. In addition, a variety of health topics, evidence-based evaluation and interpreter services are key for future success.
Value of multi-b value DWI in the assessment of early cerebral changes in asymptomatic HIV-positive adolescents
Authors: Jiang Da-Zhen , Zhou Ding-Yi , Wu Wei-Qing , Wu Guang-Yao , Quan Hong 
Published: October 2016

BackgroundMagnetic resonance imaging (MRI) and functional MRI techniques have been widely used in the diagnosis of human immunodeficiency virus (HIV) infection related diseases.PurposeTo explore whether magnetic resonance diffusion-weighted imaging (DWI) can track water molecular diffusion changes in the brain of asymptomatic HIV-positive adolescents.Material and MethodsMulti-b value DWI was performed in 23 adolescents, including 15 HIV-positive participants and eight HIV-negative healthy participants. Mean apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (ADCs) values, fast apparent diffusion coefficient (ADCf) values, distribution diffusion coefficient (DDC) values, and heterogeneity index (α) values were calculated within regions of interest (ROIs) in the frontal lobes, basal ganglia, and temporal lobe. Non-parametric tests were then performed.ResultsIn the bilateral frontal lobes, the mean α values in HIV-positive participants were significantly increased compared with those in healthy participants (right side P = 0.001; left side P = 0.000). In the left frontal lobe, the mean DDC value in HIV-positive participants was significantly increased compared with that in healthy participants ( P = 0.008). In the bilateral frontal lobes, the mean ADCf values in HIV-positive participants were significantly lower than those in healthy participants (right side P = 0.011; left side P = 0.008). In the left basal ganglia, the mean α values in HIV-positive participants were significantly lower than that in healthy participants ( P = 0.013).ConclusionMulti-b value DWI could reflect the early characteristics of water molecule diffusion in HIV infections.
Simulation-assisted teaching of graduate students in transport: A case study of the application of acausal freeware JModelica.org to solution of Sakawa’s open-loop optimal control problem for payload motion during crane boom rotation
Authors: Kostikov Alexander A , Perig Alexander V , Lozun Ruslan R 
Published: October 2016

The present article is focused on the improvement of the quality of engineering education of graduate students with a major in transport and mechanical engineering through the derivation of a numerical solution of the optimal control problem for payload swaying during crane boom slewing, formulated by Sakawa et al. For the first time, a numerical solution of Sakawa’s problem has been derived with an application of JModelica.org freeware. The fundamental difference between this solution and Sakawa’s is the imposition of a restrictive constraint on the allowable value of payload swaying during boom-driven payload motion. The solution derived by the authors for Sakawa’s problem takes exact account of the restrictive constraints on the phase variables in contrast to Sakawa’s model, where the restriction constraints on the phase variables have been approximated. The complex of authors-proposed computational algorithms was implemented with JModelica.org. The proposed open-code algorithms derive numerical data and computational plots, which enhance and expand students’ knowledge about the dynamics of guided boom-driven payload swaying during rotary crane boom slewing.
Indigenous Knowledge Approach to Successful Psychotherapies with Aboriginal Suicide Attempters
Authors: Mehl-Madrona Lewis 
Published: October 2016

Introduction: Suicide is disproportionately common among Aboriginal people in Canada. Methods: Life stories were collected from 54 Aboriginal suicide attempters in northern Saskatchewan. Constant comparison techniques and modified grounded theory identified common themes expressed. Results: Three common plots/themes preceded suicide attempts: 1) relationship breakup, usually sudden, unanticipated, involving a third person; 2) being publicly humiliated by another person(s), accompanied by high levels of shame; and 3) high levels of unremitting, chronic life stress (including poverty) with relative isolation. We found 5 common purposes for suicide attempts: 1) to “show” someone how badly they had hurt the attempter, 2) to stop the pain, 3) to save face in a difficult social situation, 4) to get revenge, and 5) don’t know/don’t remember/made sense at the time, all stated by people who were under the influence of alcohol and/or drugs at the time of their suicide attempt. We found 5 common beliefs about death: 1) you just cease to exist, and everything just disappears; 2) you go into the spirit world and can see and hear everything that is happening in this world; 3) you go to heaven or hell; 4) you go to a better place; and 5) don’t know/didn’t think about it. Discussion: The idea of personal and cultural continuity is essential to understanding suicide among First Nations youth. Interventions targeted to the individual’s beliefs about death, purpose for suicide, and consistent with the life story (plot) in which they find themselves may be more successful than one-size-fits-all programs developed outside of aboriginal communities.
Suicidal ideation and non-fatal deliberate self-harm presentations in the Kimberley from an enhanced police–mental health service notification database
Authors: McHugh Cate , Balaratnasingam Sivasankaran , Campbell Anita , Chapman Murray 
Published: October 2016

Objectives: To determine the rate of presentations for suicidal ideation and deliberate self-harm in the Kimberley region of Western Australia, characterized in terms of age, gender, rates of repetition and engagement with community mental health services. Methods: An observational study of health service presentations over 12 months. Setting: 10 sites across the region with police services were included, capturing the overwhelming majority of self-harm presentations in the region. Participants: all Indigenous presentations were analyzed. Of the 433 individuals who presented, 361 were Indigenous. Main outcome measures: suicidal phenomena, including suicidal ideation and any type of deliberate self-harm regardless of intent. Results: Analysis suggests a broadly similar age and sex stratification of self-harm in this population compared with international reports. The rates, however, are 5–20 times higher than those reported in non-Indigenous populations in Australia and abroad, depending on whether the comparison rate is calculated from population surveys or hospital presentations. Conclusions: Prevalence of suicidal phenomena is very high and is likely to be much higher than estimated by this hospital based study. Such high prevalence suggests that a population level intervention is required in addition to interventions involving clinical services.
Value of ultrasound shear wave elastography in the diagnosis of adenomyosis
Authors: Acar S , Millar E , Mitkova M , Mitkov V 
Published: October 2016

Background The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. Methods One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. Results The following values of Young’s modulus were found in subgroup A (adenomyosis): Emean – 72.7 (22.6–274.2) kPa (median, 5–95th percentiles), Emax – 94.8 (29.3–300.0) kPa, SD – 9.9 (2.6–26.3) kPa; in subgroup B (non adenomyosis) – 28.3 (12.7–59.5) kPa, 33.6 (16.0–80.8) kPa, 3.0 (1.4–15.6) kPa; in the control group – 24.4 (17.9–32.4) kPa, 29.8 (21.6–40.8) kPa, 2.3 (1.3–6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). Conclusion This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis.