bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral Delivery of an Adenoviral Vector Carrying the SOCS-1 Gene Enhances T-Cell–Mediated Antitumor Immunity By Suppressing PD-L1
Authors: Nakagawa Satoshi , Serada Satoshi , Kakubari Reisa , Hiramatsu Kosuke , Sugase Takahito , Matsuzaki Shinya , Matsuzaki Satoko , Ueda Yutaka , Yoshino Kiyoshi , Ohkawara Tomoharu , Fujimoto Minoru , Kishimoto Tadamitsu , Kimura Tadashi , Naka Tetsuji 
Published: June 2018

Abstract
Ovarian cancer is the leading cause of gynecologic cancer-related deaths and novel therapeutic strategies are required. Programmed cell death 1 and programmed cell death ligand 1 (PD-L1), which are key mediators of host immune tolerance, are associated with ovarian cancer progression. Recent evidence indicates the importance of IFNγ-induced PD-L1 for immune tolerance in ovarian cancer. This study aimed to reveal the therapeutic potential of suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of the Janus kinase (JAK)–STAT signaling pathway, for the treatment of ovarian cancer. IHC assessment revealed that patients with ovarian cancer with high intratumoral STAT1 activation exhibited poor prognosis compared with patients with low STAT1 activation (P &lt; 0.05). Stimulation of OVISE, OVTOKO, OV2944-HM-1 (HM-1), and CT26 cell lines with IFNγ induced STAT1 phosphorylation and PD-L1 expression. Adenovirus-mediated SOCS-1 gene delivery (AdSOCS-1) in HM-1 and CT26 cells in vitro potently inhibited IFNγ-induced STAT1 phosphorylation and PD-L1 upregulation, similar to the addition of JAK inhibitor I, but failed to inhibit their proliferation. Notably, intratumoral injection of AdSOCS-1, but not AdLacZ, significantly inhibited the tumor growth of HM-1 and CT26 cells subcutaneously transplanted in immunocompetent syngeneic mice. AdSOCS-1 reduced PD-L1 expression on tumors and restored the activation of tumor-infiltrating CD8+ T cells. Moreover, the antitumor effect of AdSOCS-1 was significantly attenuated by PD-L1 Fc-fusion protein administration in vivo, suggesting that the effect of AdSOCS-1 is mainly attributable to enhancement of tumor immunity. This study highlights the potential clinical utility of SOCS-1 as an immune checkpoint inhibitor. Mol Cancer Ther; 17(9); 1941–50. ©2018 AACR.
STAT3 Cyclic Decoy Demonstrates Robust Antitumor Effects in Non–Small Cell Lung Cancer
Authors: Njatcha Christian , Farooqui Mariya , Kornberg Adam , Johnson Daniel E. , Grandis Jennifer R. , Siegfried Jill M. 
Published: June 2018

AbstractConstitutively activated STAT3 plays a critical role in non–small cell lung carcinoma (NSCLC) progression by mediating proliferation and survival. STAT3 activation in normal cells is transient, making it an attractive target for NSCLC therapy. The therapeutic potential of blocking STAT3 in NSCLC was assessed utilizing a decoy approach by ligating a double-stranded 15-mer oligonucleotide that corresponds to the STAT3 response element of STAT3-target genes, to produce a cyclic STAT3 decoy (CS3D). The decoy was evaluated using NSCLC cells containing either wild-type EGFR (201T) or mutant EGFR with an additional EGFRi resistance mutation (H1975). These cells are resistant to EGFR inhibitors and require an alternate therapeutic approach. CS3D activity was compared with an inactive cyclic control oligonucleotide (CS3M) that differs by a single base pair, rendering it unable to bind to STAT3 protein. Transfection of 0.3 μmol/L of CS3D caused a 50% inhibition in proliferation in 201T and H1975 cells, relative to CS3M, and a 2-fold increase in apoptotic cells. Toxicity was minimal in normal cells. CS3D treatment caused a significant reduction of mRNA and protein expression of the STAT3 target gene c-Myc and inhibited colony formation by 70%. The active decoy decreased the nuclear pool of STAT3 compared with the mutant. In a xenograft model, treatments with CS3D (5 mg/kg) caused a potent 96.5% and 81.7% reduction in tumor growth in 201T (P &lt; 0.007) and H1975 models (P &lt; 0.0001), respectively, and reduced c-Myc and p-STAT3 proteins. Targeting STAT3 with the cyclic decoy could be an effective therapeutic strategy for NSCLC. Mol Cancer Ther; 17(9); 1917–26. ©2018 AACR.
The Future of the Global Weather Enterprise: Opportunities and Risks
Authors: Thorpe Alan , Rogers David 
Published: June 2018

AbstractThe Global Weather Enterprise (GWE) encompasses the scientific research, technology, observations, modeling, forecasting, and forecast products that need to come together to provide accurate and reliable weather information and services that save lives, protect infrastructure, and enhance economic output. It is a value chain from weather observations to, ultimately, the creation of actionable analysis-and-forecast weather information of huge benefit to society. The GWE is a supreme exemplar of the value of international cooperation, public–private engagement, and scientific and technological know-how. It has been a successful enterprise, but one that has ever-increasing requirements for continual improvement as population density increases and climate change takes place so that the impacts of weather hazards can be mitigated as far as possible. However, the GWE is undergoing a period of significant change arising, for example, from the growing need for more accurate and reliable weather information, advances coming from science and technology, and the expansion of private sector capabilities. These changes offer real opportunities for the GWE but also present a number of obstacles and risks that could, if not addressed, stifle this development, adversely impacting the societies it aims to serve. This essay aims to catalyze the GWE to address the issues collectively, by dialogue, engagement, and mutual understanding.
Geographical Distribution of Diurnal and Semidiurnal Parametric Subharmonic Instability in a Global Ocean Circulation Model
Authors: Ansong Joseph K. , Arbic Brian K. , Simmons Harper L. , Alford Matthew H. , Buijsman Maarten C. , Timko Patrick G. , Richman James G. , Shriver Jay F. , Wallcraft Alan J. 
Published: June 2018

AbstractThe evidence for, baroclinic energetics of, and geographic distribution of parametric subharmonic instability (PSI) arising from both diurnal and semidiurnal tides in a global ocean general circulation model is investigated using 1/12.5° and 1/25° simulations that are forced by both atmospheric analysis fields and the astronomical tidal potential. The paper examines whether PSI occurs in the model, and whether it accounts for a significant fraction of the tidal baroclinic energy loss. Using energy transfer calculations and bispectral analyses, evidence is found for PSI around the critical latitudes of the tides. The intensity of both diurnal and semidiurnal PSI in the simulations is greatest in the upper ocean, consistent with previous results from idealized simulations, and quickly drops off about 5° from the critical latitudes. The sign of energy transfer depends on location; the transfer is positive (from the tides to subharmonic waves) in some locations and negative in others. The net globally integrated energy transfer is positive in all simulations and is 0.5%–10% of the amount of energy required to close the baroclinic energy budget in the model. The net amount of energy transfer is about an order of magnitude larger in the 1/25° semidiurnal simulation than the 1/12.5° one, implying the dependence of the rate of energy transfer on model resolution.
The endothelial tumor suppressor p53 is essential for venous thrombus formation in aged mice
Authors: Bochenek Magdalena L. , Bauer Tobias , Gogiraju Rajinikanth , Nadir Yona , Mann Amrit , Schönfelder Tanja , Hünig Leonie , Brenner Benjamin , Münzel Thomas , Wenzel Philip , Konstantinides Stavros , Schäfer Katrin 
Published: June 2018

Key PointsDeletion of p53 in endothelial cells prevents venous thrombosis in aged, but not in adult, mice. Neutralization of heparanase in aged mice using TFPI2 peptides restores the thrombotic phenotype of adult mice.
Exploring viable geologic interpretations of gravity models using distance-based global sensitivity analysis and kernel methods
Authors: Phelps Geoff , Scheidt Celine , Caers Jef 
Published: June 2018

ABSTRACTWe have explored ways to integrate alternative geologic interpretations into the modeling of gravity data. These methods are applied to the Vaca Fault east of Fairfield, California, USA, where the structure across the fault is in question, and the Vaca Fault is used as a case study to demonstrate the method. The Vaca Fault is modeled using gravity data collected along a 10 km line perpendicular to the strike of the fault. Of particular interest is how the gravity data might inform on the dip of the Vaca Fault and thickness of the nonmarine section and whether spatial autocorrelation of density internal to the geologic units significantly influences the resulting gravity anomaly. We approach these questions by creating a suite of structural geologic models, which we then populate with geostatistically generated densities and from which the respective synthetic gravity anomalies are calculated. We perform distance-based generalized sensitivity analysis to identify which model inputs most leverage the calculated gravity anomaly. We then use multidimensional scaling to transform the gravity anomalies into a metric space and estimate the posterior probabilities of each structural geologic model using a Bayesian approach. We find that the gravity anomalies are particularly sensitive to zones of autocorrelated density values generated from geostatistical modeling. The structural geologic models most likely to produce gravity anomalies that match the observed data are the moderately dipping normal faults, 45° and 60°, although the probability that the fault dips more steeply, including in a strike slip or reverse fault orientation, is approximately 30%. The probability of a thicker nonmarine unit is 67%, more probable than a thinner nonmarine unit. This suggests that the Vaca Fault dips moderately to the east and truncates a thicker nonmarine unit, but that any further process modeling should include alternatives of the geologic structures.
Sleep disorders in psychiatry
Authors: Selsick Hugh , O'Regan David 
Published: June 2018

SUMMARYSleep medicine is a truly multidisciplinary field that covers psychiatric, neurological and respiratory conditions. As the field has developed it has become increasingly clear that there is a great deal of overlap between sleep and psychiatric disorders and it is therefore essential for psychiatrists to have some knowledge of sleep medicine. Even those disorders, such as obstructive sleep apnoea, that may seem to be outside the remit of psychiatry can have complex and important interactions with psychiatric conditions. In this article we give a brief overview of the range of sleep disorders a psychiatrist might encounter, how they are recognised, investigated and treated, and how they relate to psychiatric conditions.LEARNING OBJECTIVES•Be aware of the range of sleep disorders that might be encountered in psychiatric practice•Understand how these sleep disorders affect mental health•Have a broad understanding of how these disorders are investigated and treatedDECLARATION OF INTERESTH.S. has accepted speaker fees from Janssen Pharmaceuticals.
Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline
Authors: Lyman Gary H. , Greenlee Heather , Bohlke Kari , Bao Ting , DeMichele Angela M. , Deng Gary E. , Fouladbakhsh Judith M. , Gil Brigitte , Hershman Dawn L. , Mansfield Sami , Mussallem Dawn M. , Mustian Karen M. , Price Erin , Rafte Susan , Cohen Lorenzo 
Published: June 2018

Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Interventions of interest included mind and body practices, natural products, and lifestyle modifications. SIO systematic reviews focused on randomized controlled trials that were published from 1990 through 2015. The SIO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations in the SIO guideline—published in 2017—are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline with a few added discussion points. Recommendations Key recommendations include the following: Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-l-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment–related adverse effects. Additional information is available at: www.asco.org/supportive-care-guidelines .
Radiation biology and oncology in the genomic era
Authors: Kerns Sarah L. , Chuang Kuang-Hsiang , Hall William , Werner Zachary , Chen Yuhchyau , Ostrer Harry , West Catharine , Rosenstein Barry 
Published: June 2018

Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side effects. An individual’s radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects. Current thinking is that some will be tissue specific, and future tests will be tailored to the normal tissues at risk. The relationship between normal and tumor cell radiosensitivity is poorly understood. Data are emerging suggesting interplay between germline genetic variation and epigenetic modification with growing evidence that changes in DNA methylation regulate the radiosensitivity of cancer cells and histone acetyltransferase inhibitors have radiosensitizing effects. Changes in histone methylation can also impair DNA damage response signaling and alter radiosensitivity. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics. To address challenges in harmonizing data from multiple cohorts, the consortium established the REQUITE project to collect standardized data and genotyping for ~5,000 patients. The collection of detailed dosimetric data is important to produce validated multivariable models. Continued efforts will identify new genes that impact on radiosensitivity to generate new knowledge on toxicity pathogenesis and tests to incorporate into the clinical decision-making process.
Contracts for Healthcare Referral Services: Coordination via Outcome-Based Penalty Contracts
Authors: Adida Elodie , Bravo Fernanda 
Published: June 2018

This work focuses on the business-to-business interaction between a service requester and a service provider in a healthcare environment. The requester is the primary caregiver responsible for managing the health of a population of patients. When a patient requires advanced care outside of the requester’s expertise, the requester refers the patient to a provider and pays for the referral services. Treatment may succeed or fail, and in the case of failure, the requester incurs further follow-up costs. The requester may exert preventive effort to reduce the volume of referrals. The provider may exert nonreimbursable effort to reduce the chance of treatment failure. We analyze payment contracts between the two firms. We find that fee-for-service (FFS) induces neither system nor social optimum effort outcomes. However, a penalty contract can generally coordinate the effort decisions with either the system optimum or the social optimum. Furthermore, we find that patients may benefit from having a coordinating contract replace FFS. However, the types of procedures that make a coordinating contract most advantageous for the requester and provider are not necessarily the same as those that make the patients better off than under FFS. Yet, in most cases, the coordinating contract improves social welfare, as compared to FFS, and brings it close to the social optimum. Hence, the requester–provider coordinating contract can be considered as an improvement over FFS for the entire system. The online appendix is available at https://doi.org/10.1287/mnsc.2017.3000 . This paper was accepted by Serguei Netessine, operations management.
Does Transparency Stifle or Facilitate Innovation?
Authors: Brown James R. , Martinsson Gustav 
Published: June 2018

Corporate transparency reduces information asymmetries between firms and capital markets but increases the costs associated with information leakage to competitors. We explore how a country’s information environment affects innovation, an activity characterized by high information asymmetries and potentially severe proprietary costs. Studying both long-run cross-country differences in the availability of firm-specific information to corporate outsiders, as well as quasi-experimental shocks to the information environment following transparency-enhancing security market reforms, we document significantly higher rates of R&D and patenting in richer information environments. The effects of transparency are strongest in industries that rely on external equity rather than bank debt, indicating that transparency facilitates innovation by reducing the information costs associated with arm’s-length financing. In contrast, transparency has no impact on physical capital accumulation, consistent with fewer information asymmetries in tangible assets. An economy’s information environment has important but heterogeneous effects on the nature and extent of real economic activity.This paper was accepted by Shiva Rajgopal, accounting.
Power-assisted exercise for people with complex neurological impairment: a feasibility study
Authors: Young Rachel Elizabeth , Richards Emma , Darji Neha , Velpula Suchitra , Goddard Sara , Smith Christine , Broom David 
Published: June 2018

Background/Aims: Participation in physical activity and exercise presents a challenge for adults with complex neurological impairment. Power-assisted exercise facilitates combined limb and trunk movement and may be an option for people with movement impairment. The aim of this study was to determine whether power-assisted exercise is a feasible activity option for people with complex neurological impairment. Methods: Seven adults with complex neurological impairment were recruited to take part in a 4-week programme of twice weekly power-assisted exercise. Programme attendance and completion was recorded and adverse events or effects documented. Mobility was monitored using the Timed Up and Go test (TUG). Upon completion of the programme, participants were interviewed regarding their experience of using the equipment. Findings: All seven participants completed the programme and the overall attendance was 96%. No adverse events occurred; two participants reported minor adverse effects, which were temporary. The TUG scores improved and participants enjoyed the programme, reporting perceived benefits in physical function and wellbeing. Conclusions: The findings of this study demonstrate that people with complex neurological impairment can participate in a programme of power-assisted exercise. Reported improvements in physical mobility suggest that further research in this area is indicated.
Training healthy persons and individuals with Parkinson's disease to use Xbox Kinect games: a preliminary study
Authors: Dantas Isabela Viana , Leal Josevan Cerqueira , Hilgert Luiza Saboya , Allegretti Ana Luiza Caltabiano , Dos Santos Mendes Felipe Augusto 
Published: June 2018

Background/Aims: Individuals with Parkinson's disease, besides the motor and cognitive symptoms may even present deficits in the motor learning. A recent therapeutic approach involves virtual reality that offers elements that can minimize the difficulties in the learning process. Recently, the therapeutic potential of Nintendo Wii® gaming device for rehabilitation of patients with Parkinson's disease has been showing positive results, but studies related to the use of the Kinect for XboxTM are still scarce. The present study aimed to investigate the effects of motor and cognitive demands of six Kinect for Xbox 360TM games on the learning of patients with Parkinson's disease, comparing it with healthy individuals. Methods: A total of 19 adults, 8 with idiopathic Parkinson's disease and 11 healthy adults participated in a program which included 10 training sessions and had their scores registered three times. Findings: The results showed that in four of those games, patients with Parkinson's disease showed an ability to improve and keep their performance, but not in the other two games, similar to healthy adults. Conclusions: It was concluded that motor and cognitive abilities affected by Parkinson's disease may be improved with the use of virtual training proposed in this study. Some of the games and gaming devices features can influence the learning process, even in healthy adults.
Neural Correlates of Odor Learning in the Presynaptic Microglomerular Circuitry in the Honeybee Mushroom Body Calyx
Authors: Haenicke Joachim , Yamagata Nobuhiro , Zwaka Hanna , Nawrot Martin , Menzel Randolf 
Published: June 2018

AbstractThe mushroom body (MB) in insects is known as a major center for associative learning and memory, although exact locations for the correlating memory traces remain to be elucidated. Here, we asked whether presynaptic boutons of olfactory projection neurons (PNs) in the main input site of the MB undergo neuronal plasticity during classical odor-reward conditioning and correlate with the conditioned behavior. We simultaneously measured Ca2+responses in the boutons and conditioned behavioral responses to learned odors in honeybees. We found that the absolute amount of the neural change for the rewarded but not for the unrewarded odor was correlated with the behavioral learning rate across individuals. The temporal profile of the induced changes matched with odor response dynamics of the MB-associated inhibitory neurons, suggestive of activity modulation of boutons by this neural class. We hypothesize the circuit-specific neural plasticity relates to the learned value of the stimulus and underlies the conditioned behavior of the bees.