bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species
Authors: Warfel Noel A. , Sainz Alva G. , Song Jin H. , Kraft Andrew S. 
Published: May 2016

Abstract
Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases represent a prosurvival pathway that is upregulated in response to hypoxia, in a HIF-1–independent manner. We demonstrate that pharmacologic or genetic inhibition of PIM kinases is significantly more toxic toward cancer cells in hypoxia as compared with normoxia. Xenograft studies confirm that PIM kinase inhibitors impede tumor growth and selectively kill hypoxic tumor cells in vivo. Experiments show that PIM kinases enhance the ability of tumor cells to adapt to hypoxia-induced oxidative stress by increasing the nuclear localization and activity of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which functions to increase the expression of antioxidant genes. Small molecule PIM kinase inhibitors prevent Nrf2 from accumulating in the nucleus, reducing the transcription of cytoprotective genes and leading to the build-up of intracellular reactive oxygen species (ROS) to toxic levels in hypoxic tumor cells. This toxic effect of PIM inhibitors can be successfully blocked by ROS scavengers, including N-acetyl cystine and superoxide dismutase. Thus, inhibition of PIM kinases has the potential to oppose hypoxia-mediated therapeutic resistance and induce cell death in the hypoxic tumor microenvironment. Mol Cancer Ther; 15(7); 1637–47. ©2016 AACR.
Additional species and records of the “horn-backed” Pilophorus plant bugs in Southeast Asia (Heteroptera: Miridae: Phylinae)
Authors: Nakatani Y. , Komatsu T. , Shimizu-kaya U. , Itioka T. , Itino T. , Hashim R. , Ueda S. , Asfiya W. , Herwina H. , Hartini S. 
Published: May 2016

Three new species of the “horn-backed” phyline plant bug genus Pilophorus Hahn, namely, P. erinaceulus, P. maruyamai and P. parvolus, are described from Borneo, Malaysia and Sumatra, Indonesia. The following species are newly recorded within Southeast Asia: P. lambirensis from the Malay Peninsula; P. laticollaris from Sumatra; P. longirostris and P. multivillus from Borneo. A supplementary key to the key by Nakatani et al. (2013) is provided.
Y. Nakatani*, Natural Resources Inventory Center, National Institute for Agro-Environmental Sciences, Kannondai, 3-1-3, Tsukuba, Ibaraki, 305-8604, Japan. nakatany@affrc.go.jp
T. Komatsu, Institute of Tropical Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan. corocoro1232000@yahoo.co.jp
U. Shimizu-kaya, Center for Ecological Research, Kyoto University, Hirano, Otsu, Shiga 520-2113, Japan. shimizu.kaya.55c@st.kyoto-u.ac.jp
T. Itioka, Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan. ichioka.takao.5m@kyoto-u.ac.jp
T. Itino, S. Ueda, Department of Biology, Faculty of Science, Shinshu University 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. ueda32@shinshu-u.ac.jp
R. Hashim, Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. rh4758@gmail.com
W. Asfiya, S. Hartini, Division of Zoology, Research Center for Biology, Indonesian Institute of Sciences, Jl. Raya Jakarta-Bogor Km. 46, Cibinong, Bogor, 16911, Indonesia. wara.asfiya@lipi.go.id
H. Herwina, Laboratorium Riset Taksonomi Hewan, Jurusan Biologi, Fakultas Matematika dan Ilmu Pengetahuan Alam, Universitas Andalas, Kampus UNAND Limau Manis, Padang, 25163, Indonesia. hennyf91@gmail.com
Hydrometeor Mixing Ratio Retrievals for Storm-Scale Radar Data Assimilation: Utility of Current Relations and Potential Benefits of Polarimetry
Authors: Carlin Jacob T. , Ryzhkov Alexander V. , Snyder Jeffrey C. , Khain Alexander 
Published: May 2016

Abstract
The assimilation of radar data into storm-scale numerical weather prediction models has been shown to be beneficial for successfully modeling convective storms. Because of the difficulty of directly assimilating reflectivity (Z), hydrometeor mixing ratios, and sometimes rainfall rate, are often retrieved from Z observations using retrieval relations, and are assimilated as state variables. The most limiting (although widely employed) cases of these relations are derived, and their assumptions and limitations are discussed.
To investigate the utility of these retrieval relations for liquid water content (LWC) and ice water content (IWC) in rain and hail as well as the potential for improvement using polarimetric variables, two models with spectral bin microphysics coupled with a polarimetric radar operator are used: a one-dimensional melting hail model and the two-dimensional Hebrew University Cloud Model. The relationship between LWC and Z in pure rain varies spatially and temporally, with biases clearly seen using the normalized number concentration. Retrievals using Z perform the poorest while specific attenuation and specific differential phase shift (KDP) perform much better. Within rain–hail mixtures, separate estimation of LWC and IWC is necessary. Prohibitively large errors in the retrieved LWC may result when using Z. The quantity KDP can be used to effectively retrieve the LWC and to isolate the contribution of IWC to Z. It is found that the relationship between Z and IWC is a function of radar wavelength, maximum hail diameter, and principally the height below the melting layer, which must be accounted for in order to achieve accurate retrievals.
Influence of Playing a Prolonged Tennis Match on Shoulder Internal Range of Motion
Authors: Martin Caroline , Kulpa Richard , Ezanno Felix , Delamarche Paul , Bideau Benoit 
Published: May 2016

Background: Shoulder range of motion (ROM) deficits have been identified as an injury risk factor among tennis players. It is well known that shoulder internal rotation deficit increases with age and years of play, but there is a lack of knowledge regarding the influence of a prolonged tennis match on shoulder ROM. Purpose: To examine changes in shoulder ROM during a prolonged tennis match. Study Design: Descriptive laboratory study. Methods: Shoulder passive internal and external rotation ROM were measured on 8 male tennis players before, every 30 minutes during, and just after a 3-hour tennis match. Total ROM was calculated as the combination of shoulder internal and external rotations. Ball velocity on the serve was measured with a radar gun before, at midmatch, and just after the match. Results: Decreases in shoulder internal rotation (–20.8°; P = .005), total ROM (–24.6°; P = .001), and serve velocity (–1.8 m/s; P = .002) were observed at the end of the match. No statistically significant difference was observed for shoulder external rotation after the match ( P = .460). Conclusion: Passive shoulder internal rotation and total ROM are significantly decreased during a 3-hour tennis match. Clinical Relevance: The results show that a prolonged tennis match play can modify values of shoulder ROM.
St George Acute Care Team: the local variant of crisis resolution model of care
Authors: Cupina Denise D , Wand Anne P F , Phelan Emma , Atkin Rona 
Published: May 2016

Objectives: The objective of this study was to describe functioning and clinical activities of the St George Acute Care Team and how it compares to the typical crisis resolution model of care. Methods: Descriptive data including demographics, sources of referral, type of clinical intervention, length of stay, diagnoses and outcomes were collected from records of all patients who were discharged from the team during a 10 week period. Results: There were 677 referrals. The team’s functions consisted of post-discharge follow-up (31%), triage and intake (30%), case management support (23%) and acute community based assessment and treatment (16%). The average length of stay was 5 days. The majority of patients were diagnosed with a mood (23%) or a psychotic (25%) disorder. Points of contrast to other reported crisis resolution teams include shorter length of stay, relatively less focus on direct clinical assessment and more telephone follow-up and triage. Conclusion: St George Acute Care Team provides a variety of clinical activities. The focus has shifted away from the original model of crisis resolution care to meet local and governmental requirements.
Damage detection in wind turbine blades by using operational modal analysis
Authors: Lorenzo Emilio Di , Petrone Giuseppe , Manzato Simone , Peeters Bart , Desmet Wim , Marulo Francesco 
Published: May 2016

In this paper a vibration-based approach to identify a crack in a wind turbine blade is described and demonstrated numerically and experimentally. Operational modal analysis has been performed before and after a buckling test, and vibration data, gathered from some accelerometers placed along the blade, was used to monitor the integrity of the structure, since the modal parameters are directly influenced by the physical properties of the structures. Additionally a numerical prediction has been done both with a full-scale model and with a one-dimensional model. The results show that this approach is able to estimate successfully the presence of damage and a good numerical and experimental correlation has been found. Finally, some considerations regarding the rotation of the blade in the undamaged and damaged cases have been done.
Trust in interprofessional collaboration
Authors: Gregory Paul A. M. , Austin Zubin 
Published: May 2016

Background: Trust is integral to effective interprofessional collaboration. There has been scant literature characterizing how trust between practitioners is formed, maintained or lost. The objective of this study was to characterize the cognitive model of trust that exists between pharmacists and family physicians working in collaborative primary care settings. Methods: Pharmacists and family physicians who work collaboratively in primary care were participants in this study. Family health teams were excluded from this study because of the distinct nature of these settings. Through a snowball convenience sampling method, a total of 11 pharmacists and 8 family physicians were recruited. A semistructured interview guide was used to guide discussion around trust, relationships and collaboration. Constant-comparative coding was used to identify themes emerging from these data. Results: Pharmacists and family physicians demonstrate different cognitive models of trust in primary care collaboration. For pharmacists, trust appears to be conferred on physicians based on title, degree, status and positional authority. For family physicians, trust appears to be earned based on competency and performance. These differences may lead to interprofessional tension when expectations of reciprocal trust are not met. Conclusions: Further work in characterizing how trust is developed in interprofessional relationships is needed to support effective team formation and functioning.
Downregulation of Cdh1 signalling in spinal dorsal horn contributes to the maintenance of mechanical allodynia after nerve injury in rats
Authors: Hu Rong , Li Li , Li Dajia , Tan Wei , Wan Li , Zhu Chang , Zhang Yue , Zhang Chuanhan , Yao Wenlong 
Published: May 2016

Background Anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 are important ubiquitin-ligases in proliferating cells and terminally differentiated neurons. In recent years, APC/C-Cdh1 has been reported as an important complex contributing to synaptic development and transmission. Interestingly, cortical APC/C-Cdh1 is found to play a critical role in the maintenance of neuropathic pain, but it is not clear whether APC/C-Cdh1 in spinal dorsal cord is involved in molecular mechanisms of neuropathic pain conditions. Results Immunostaining showed that Cdh1 was mainly distributed in dorsal horn neurons of the spinal cord in rats. Its expression was downregulated in the ipsilateral dorsal horn at 14 days after spared nerve injury. Rescued expression of Cdh1 in spinal cord by intrathecal administration of recombinant lentivirus encoding Cdh1 (Lenti-Cdh1-GFP) significantly attenuated spared nerve injury-induced mechanical allodynia. Furthermore, rescued expression of spinal Cdh1 significantly reduced surface membrane expression of GluR1, but increased the expression of GluR1-related erythropoietin-producing human hepatocellular receptor A4 and its ligand EphrinA1 in dorsal horn of spared nerve injury-treated animals. Conclusions This study indicates that a downregulation of Cdh1 expression in spinal dorsal horn is involved in molecular mechanisms underlying the maintenance of neuropathic pain. Upregulation of spinal Cdh1 may be a promising approach to treat neuropathic pain.
BLVRB redox mutation defines heme degradation in a metabolic pathway of enhanced thrombopoiesis in humans
Authors: Wu Song , Li Zongdong , Gnatenko Dmitri V. , Zhang Beibei , Zhao Lu , Malone Lisa E. , Markova Nedialka , Mantle Timothy J. , Nesbitt Natasha M. , Bahou Wadie F. 
Published: May 2016

Key PointsA biliverdin IXβ reductase redox coupling mutation with associated ROS dysregulation has been identified in thrombocytosis cohorts. Defective BLVRB enzymatic activity involving heme degradation pathway alters metabolic consequences of hematopoietic lineage fate.
A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer)
Authors: Berkowitz Nathan D. , Silverman Ian M. , Childress Daniel M. , Kazan Hilal , Wang Li-San , Gregory Brian D. 
Published: May 2016

Abstract
Background
RNA molecules fold into complex three-dimensional shapes, guided by the pattern of hydrogen bonding between nucleotides. This pattern of base pairing, known as RNA secondary structure, is critical to their cellular function. Recently several diverse methods have been developed to assay RNA secondary structure on a transcriptome-wide scale using high-throughput sequencing. Each approach has its own strengths and caveats, however there is no widely available tool for visualizing and comparing the results from these varied methods.

Methods
To address this, we have developed Structure Surfer, a database and visualization tool for inspecting RNA secondary structure in six transcriptome-wide data sets from human and mouse (http://tesla.pcbi.upenn.edu/strucuturesurfer/). The data sets were generated using four different high-throughput sequencing based methods. Each one was analyzed with a scoring pipeline specific to its experimental design. Users of Structure Surfer have the ability to query individual loci as well as detect trends across multiple sites.

Results
Here, we describe the included data sets and their differences. We illustrate the database’s function by examining known structural elements and we explore example use cases in which combined data is used to detect structural trends.

Conclusions
In total, Structure Surfer provides an easy-to-use database and visualization interface for allowing users to interrogate the currently available transcriptome-wide RNA secondary structure information for mammals.
Randomized Phase II Study of Trabectedin and Doxorubicin Compared With Doxorubicin Alone as First-Line Treatment in Patients With Advanced Soft Tissue Sarcomas: A Spanish Group for Research on Sarcoma Study
Authors: Martin-Broto Javier , Pousa Antonio López , de las Peñas Ramón , García del Muro Xavier , Gutierrez Antonio , Martinez-Trufero Javier , Cruz Josefina , Alvarez Rosa , Cubedo Ricardo , Redondo Andrés , Maurel Joan , Carrasco Juan A. , López-Martin José A. , Sala Ángeles , Meana José Andrés , Ramos Rafael , Martinez-Serra Jordi , Lopez-Guerrero José A. , Sevilla Isabel , Balaña Carmen , Vaz Ángeles , De Juan Ana , Alemany Regina , Poveda Andrés 
Published: May 2016

Purpose Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. Patients and Methods In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m2 in a 3-hour infusion plus doxorubicin 60 mg/m2 as the experimental arm and doxorubicin 75 mg/m2 as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. Results In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53−; 3.4 months if FAS+/p53+ or FAS−/p53−; and 0.7 months if FAS− and p53+; P < .001) and for overall survival. Conclusion Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line.
Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer
Authors: Hurria Arti , Mohile Supriya , Gajra Ajeet , Klepin Heidi , Muss Hyman , Chapman Andrew , Feng Tao , Smith David , Sun Can-Lan , De Glas Nienke , Cohen Harvey Jay , Katheria Vani , Doan Caroline , Zavala Laura , Levi Abrahm , Akiba Chie , Tew William P. 
Published: May 2016

Purpose Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). Patients and Methods Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. Results The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). Conclusion This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.
Risk Stratification of Neck Lesions Detected Sonographically During the Follow-Up of Differentiated Thyroid Cancer
Authors: Lamartina Livia , Grani Giorgio , Biffoni Marco , Giacomelli Laura , Costante Giuseppe , Lupo Stefania , Maranghi Marianna , Plasmati Katia , Sponziello Marialuisa , Trulli Fabiana , Verrienti Antonella , Filetti Sebastiano , Durante Cosimo 
Published: May 2016

Context:The European Thyroid Association (ETA) has classified posttreatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence.Objective:The objective of the study was to assess this classification's ability to predict the growth and persistence of such lesions during active posttreatment surveillance of patients with differentiated thyroid cancer (DTC).Design:This was a retrospective, observational study.Setting:The study was conducted at a thyroid cancer center in a large Italian teaching hospital.Patients:Center referrals (2005–2014) were reviewed and patients selected with pathologically-confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on two or more consecutive posttreatment neck sonograms; and subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with one or more lesions classified as suspicious) and group I (indeterminate lesions only). We recorded baseline and follow-up clinical data through June 30, 2015.Main Outcomes:The main outcomes were patients with growth (&gt;3 mm, largest diameter) of one or more lesions during follow-up and patients with one or more persistent lesions at the final visit.Results:The cohort included 58 of the 637 DTC cases screened (9%). A total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group I had significantly lower rates than group S of lesion growth (8% vs 36%, P = .01) and persistence (64% vs 97%, P = .014). The median time to scan normalization was 2.9 years.Conclusions:The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify papillary thyroid cancer patients eligible for more relaxed follow-up.
The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis in Drosophila
Authors: Wang Zhenghan , Tian Ai , Benchabane Hassina , Tacchelly-Benites Ofelia , Yang Eungi , Nojima Hisashi , Ahmed Yashi 
Published: May 2016

ABSTRACT
Wnt/β-catenin signaling controls intestinal stem cell (ISC) proliferation, and is aberrantly activated in colorectal cancer. Inhibitors of the ADP-ribose polymerase Tankyrase (Tnks) have become lead therapeutic candidates for Wnt-driven cancers, following the recent discovery that Tnks targets Axin, a negative regulator of Wnt signaling, for proteolysis. Initial reports indicated that Tnks is important for Wnt pathway activation in cultured human cell lines. However, the requirement for Tnks in physiological settings has been less clear, as subsequent studies in mice, fish and flies suggested that Tnks was either entirely dispensable for Wnt-dependent processes in vivo, or alternatively, had tissue-specific roles. Here, using null alleles, we demonstrate that the regulation of Axin by the highly conserved Drosophila Tnks homolog is essential for the control of ISC proliferation. Furthermore, in the adult intestine, where activity of the Wingless pathway is graded and peaks at each compartmental boundary, Tnks is dispensable for signaling in regions where pathway activity is high, but essential where pathway activity is relatively low. Finally, as observed previously for Wingless pathway components, Tnks activity in absorptive enterocytes controls the proliferation of neighboring ISCs non-autonomously by regulating JAK/STAT signaling. These findings reveal the requirement for Tnks in the control of ISC proliferation and suggest an essential role in the amplification of Wnt signaling, with relevance for development, homeostasis and cancer.