bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study
Authors: Lamberts Laetitia E. , Koch Maximillian , de Jong Johannes S. , Adams Arthur L.L. , Glatz Jürgen , Kranendonk Mariëtte E.G. , Terwisscha van Scheltinga Anton G.T. , Jansen Liesbeth , de Vries Jakob , Lub-de Hooge Marjolijn N. , Schröder Carolien P. , Jorritsma-Smit Annelies , Linssen Matthijs D. , de Boer Esther , van der Vegt Bert , Nagengast Wouter B. , Elias Sjoerd G. , Oliveira Sabrina , Witkamp Arjen J. , Mali Willem P.Th.M. , Van der Wall Elsken , van Diest Paul J. , de Vries Elisabeth G.E. , Ntziachristos Vasilis , van Dam Gooitzen M. 
Published: November 2016

Abstract
Purpose: To provide proof of principle of safety, breast tumor–specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab–IRDye800CW targeting VEGF-A in patients with breast cancer.
Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab–IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.
Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P &lt; 0.05) and healthy tissue (P &lt; 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P &lt; 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.
Conclusions: Our study shows that systemic administration of the bevacizumab–IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. Clin Cancer Res; 23(11); 2730–41. ©2016 AACR.
Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei
Authors: Dillon Magnus T. , Barker Holly E. , Pedersen Malin , Hafsi Hind , Bhide Shreerang A. , Newbold Kate L. , Nutting Christopher M. , McLaughlin Martin , Harrington Kevin J. 
Published: November 2016

AbstractAZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by AZD6738 to single radiation fractions in multiple cancer cell lines independent of both p53 and BRCA2 status by the clonogenic assay. Radiosensitization by AZD6738 to clinically relevant doses of fractionated radiation was demonstrated in vitro using a 3D tumor spheroid model and, in vivo, AZD6738 radiosensitized by abrogating the radiation-induced G2 cell-cycle checkpoint and inhibiting homologous recombination. Mitosis with damaged DNA resulted in mitotic catastrophe as measured by micronucleus formation by live-cell fluorescent-ubiquitination cell-cycle imaging of cell-cycle progression and nuclear morphology. Induction of micronuclei was significantly more prominent for AZD6738 compared with inhibition of the downstream kinase CHK1 alone at isoeffective doses. Micronuclei were characterized as acentric chromosomal fragments, which displayed characteristics of increased DNA damage and cell-cycle dyssynchrony when compared with the primary nucleus. Mol Cancer Ther; 16(1); 25–34. ©2016 AACR.
Targeting Inflammation in Cancer Prevention and Therapy
Authors: Todoric Jelena , Antonucci Laura , Karin Michael 
Published: November 2016

AbstractInflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol, and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common nonsteroidal anti-inflammatory drugs (NSAID) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches on the basis of tumor resection, radiation, and cytotoxic chemicals. Cancer Prev Res; 9(12); 895–905. ©2016 AACR.
You Can't Always Get What You Want: Why Foreign-Imposed Regime Change Seldom Improves Interstate Relations
Authors: Downes Alexander B. , O'Rourke Lindsey A. 
Published: November 2016

Abstract
States frequently employ overt and covert foreign-imposed regime change (FIRC) to pursue their foreign policy interests. Yet there is little scholarship on the question of whether FIRCs improve relations between the states involved. In fact, most FIRCs either fail to reduce—or increase—the likelihood of militarized disputes between interveners and targets. Fundamentally, FIRC entails a principal-agent problem: foreign-imposed leaders rule over states with interests different from those of the intervener. Whereas the intervening state wants the new leader to pursue policies that reflect its interests, once in power, such leaders are focused on ensuring their political survival, a task that is often undermined by implementing the intervener's agenda. Foreign-imposed leaders who carry out the intervener's desired policies attract the ire of domestic actors. These domestic opponents can force the regime to reverse course or may even remove it from power in favor of leaders who are hostile to the intervener; in both cases, the result can be renewed conflict with the intervener. Rwanda's replacement of Mobutu Sese Seko with Laurent-Désiré Kabila in Zaire illustrates this problem.
A Mass-Flux Cumulus Parameterization Scheme across Gray-Zone Resolutions
Authors: Kwon Young Cheol , Hong Song-You 
Published: November 2016

AbstractA method that enables a mass-flux cumulus parameterization scheme (CPS) to work seamlessly in various model grids across CPS gray-zone resolutions is proposed. The convective cloud-base mass flux, convective inhibition, and convective detrainment in the simplified Arakawa–Schubert (SAS) scheme are modified to be functions of the convective updraft fraction. The combination of two updraft fractions is used to modulate the cloud-base mass flux; the first one depends on the horizontal grid space and the other is a function of the grid-scale and convective vertical velocity. The convective inhibition and detrainment of hydrometeors are also modified to be a function of the grid-size-dependent convective updraft fraction.A set of sensitivity experiments with the Weather Research and Forecasting (WRF) Model is conducted for a heavy rainfall case over South Korea. The results show that the revised SAS CPS outperforms the original SAS. At 3 and 1 km, the precipitation core over South Korea is well reproduced by the experiments with the revised SAS scheme. On the contrary, the simulated precipitation is widespread in the case of the original SAS experiment and there are multiple spurious cores when the CPS is removed at those resolutions. The modified mass flux at the cloud base is found to play a major role in organizing the grid-scale precipitation at the convective core. A 1-month simulation at 3 km confirms that the revised scheme produces slightly better summer monsoonal precipitation results as compared to the typical model setup without CPS.
High‐Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double‐Blind, Randomized, Placebo‐Controlled Trial
Authors: Smith Ellen M. , Jones Jennifer L. , Han Jenny E. , Alvarez Jessica A. , Sloan John H. , Konrad Robert J. , Zughaier Susu M. , Martin Greg S. , Ziegler Thomas R. , Tangpricha Vin 
Published: November 2016

AbstractBackground: Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high‐dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. Materials and Methods: Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double‐blind, randomized, placebo‐controlled trial of high‐dose vitamin D3 (D3) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3, or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3, respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed‐effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. Results: At enrollment, >75% of participants in all groups had plasma 25‐hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000‐IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000‐IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000‐IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000‐IU D3 group. Conclusion: In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high‐dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.
Radial shortening osteotomy for treatment of Lichtman Stage IIIA Kienböck disease
Authors: Luegmair M. , Goehtz F. , Kalb K. , Cip J. , van Schoonhoven J. 
Published: November 2016

We carried out a retrospective study to analyse the long-term outcome of 36 patients after radial shortening osteotomy for treatment of Lichtman Stage IIIA Kienböck disease at a mean follow-up of 12.1 years (range 5.4–17.5). At review, seven wrists had progressed to Stage IIIB, eight wrists to Stage IV and 21 remained in Stage IIIA. Motion and grip strength were significantly improved. The mean Disabilities of the Arm, Shoulder, and Hand (DASH) score at review was 12 points (range 0–52), and patient satisfaction was high. Apart from plate removals in 14 patients and one wrist denervation, no subsequent surgical procedures were done. Radial shortening yields good long-term clinical results, but does not prevent radiographic progression of disease in some patients. Level of evidence: Therapeutic IV
How I evaluate and treat thrombocytopenia in the intensive care unit patient
Authors: Greinacher Andreas , Selleng Sixten 
Published: November 2016

AbstractMultiple causes (pseudothrombocytopenia, hemodilution, increased consumption, decreased production, increased sequestration, and immune-mediated destruction of platelets) alone or in combination make thrombocytopenia very common in intensive care unit (ICU) patients. Persisting thrombocytopenia in critically ill patients is associated with, but not causative of, increased mortality. Identification of the underlying cause is key for management decisions in individual patients. While platelet transfusion might be indicated in patients with impaired platelet production or increased platelet destruction, it could be deleterious in patients with increased intravascular platelet activation. Sepsis and trauma are the most common causes of thrombocytopenia in the ICU. In these patients, treatment of the underlying disease will also increase platelet counts. Heparin-induced thrombocytopenia requires alternative anticoagulation at a therapeutic dose and immune thrombocytopenia immunomodulatory treatment. Thrombocytopenia with symptomatic bleeding at or above World Health Organization grade 2 or planned invasive procedures are established indications for platelet transfusions, while the evidence for a benefit of prophylactic platelet transfusions is weak and controversial. If the platelet count does not increase after transfusion of 2 fresh ABO blood group–identical platelet concentrates (therapeutic units), ongoing platelet consumption and high-titer anti-HLA class I antibodies should be considered. The latter requires transfusion of HLA-compatible platelet concentrates.
Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model
Authors: Ni Jingchao , Koyuturk Mehmet , Tong Hanghang , Haines Jonathan , Xu Rong , Zhang Xiang 
Published: November 2016

Abstract
Background
Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although successful, a common limitation of the existing methods is that they assume all diseases share the same molecular network and a single generic molecular network is used to predict candidate genes for all diseases. However, different diseases tend to manifest in different tissues, and the molecular networks in different tissues are usually different. An ideal method should be able to incorporate tissue-specific molecular networks for different diseases.

Results
In this paper, we develop a robust and flexible method to integrate tissue-specific molecular networks for disease gene prioritization. Our method allows each disease to have its own tissue-specific network(s). We formulate the problem of candidate gene prioritization as an optimization problem based on network propagation. When there are multiple tissue-specific networks available for a disease, our method can automatically infer the relative importance of each tissue-specific network. Thus it is robust to the noisy and incomplete network data. To solve the optimization problem, we develop fast algorithms which have linear time complexities in the number of nodes in the molecular networks. We also provide rigorous theoretical foundations for our algorithms in terms of their optimality and convergence properties. Extensive experimental results show that our method can significantly improve the accuracy of candidate gene prioritization compared with the state-of-the-art methods.

Conclusions
In our experiments, we compare our methods with 7 popular network-based disease gene prioritization algorithms on diseases from Online Mendelian Inheritance in Man (OMIM) database. The experimental results demonstrate that our methods recover true associations more accurately than other methods in terms of AUC values, and the performance differences are significant (with paired t-test p-values less than 0.05). This validates the importance to integrate tissue-specific molecular networks for studying disease gene prioritization and show the superiority of our network models and ranking algorithms toward this purpose. The source code and datasets are available at http://nijingchao.github.io/CRstar/.
libFLASM: a software library for fixed-length approximate string matching
Authors: Ayad Lorraine A. K. , Pissis Solon P. , Retha Ahmad 
Published: November 2016

Abstract
Background
Approximate string matching is the problem of finding all factors of a given text that are at a distance at most k from a given pattern. Fixed-length approximate string matching is the problem of finding all factors of a text of length n that are at a distance at most k from any factor of length ℓ of a pattern of length m. There exist bit-vector techniques to solve the fixed-length approximate string matching problem in time $\mathcal {O}(m\lceil \ell /w \rceil n)$
O
(
m
⌈
ℓ
/
w
⌉
n
)
and space $\mathcal {O}(m\lceil \ell /w\rceil)$
O
(
m
⌈
ℓ
/
w
⌉
)
under the edit and Hamming distance models, where w is the size of the computer word; as such these techniques are independent of the distance threshold k or the alphabet size. Fixed-length approximate string matching is a generalisation of approximate string matching and, hence, has numerous direct applications in computational molecular biology and elsewhere.

Results
We present and make available , a free open-source software library for solving fixed-length approximate string matching under both the edit and the Hamming distance models. Moreover we describe how fixed-length approximate string matching is applied to solve real problems by incorporating into established applications for multiple circular sequence alignment as well as single and structured motif extraction. Specifically, we describe how it can be used to improve the accuracy of multiple circular sequence alignment in terms of the inferred likelihood-based phylogenies; and we also describe how it is used to efficiently find motifs in molecular sequences representing regulatory or functional regions. The comparison of the performance of the library to other algorithms show how it is competitive, especially with increasing distance thresholds.

Conclusions
Fixed-length approximate string matching is a generalisation of the classic approximate string matching problem. We present , a free open-source software library for solving fixed-length approximate string matching. The extensive experimental results presented here suggest that other applications could benefit from using , and thus further maintenance and development of is desirable.
High resolution microscopy reveals the nuclear shape of budding yeast during cell cycle and in various biological states
Authors: Wang Renjie , Kamgoue Alain , Normand Christophe , Léger-Silvestre Isabelle , Mangeat Thomas , Gadal Olivier 
Published: November 2016

ABSTRACT
How spatial organization of the genome depends on nuclear shape is unknown, mostly because accurate nuclear size and shape measurement is technically challenging. In large cell populations of the yeast Saccharomyces cerevisiae, we assessed the geometry (size and shape) of nuclei in three dimensions with a resolution of 30 nm. We improved an automated fluorescence localization method by implementing a post-acquisition correction of the spherical microscopic aberration along the z-axis, to detect the three dimensional (3D) positions of nuclear pore complexes (NPCs) in the nuclear envelope. Here, we used a method called NucQuant to accurately estimate the geometry of nuclei in 3D throughout the cell cycle. To increase the robustness of the statistics, we aggregated thousands of detected NPCs from a cell population in a single representation using the nucleolus or the spindle pole body (SPB) as references to align nuclei along the same axis. We could detect asymmetric changes of the nucleus associated with modification of nucleolar size. Stereotypical modification of the nucleus toward the nucleolus further confirmed the asymmetric properties of the nuclear envelope.
Relationship between cytokines and running economy in marathon runners
Authors: Luna Junior Luiz Antonio , de Melo Batista dos Santo Juliana , Lacerda Bachi André Luis , Foster Roberta , Slowetzky Amaro Alexandre , Ligeiro de Oliveira Ana Paula , Rennó Sierra Ana Paula , Peduti Dal Molin Kiss Maria Augusta , Vaisberg Mauro Walter 
Published: November 2016

AbstractBackgroundRunning economy (RE), expresses the relationship between the energy cost of running (Cr) and the work performed by a runner and is an predictor of performance. Given the intense effort of marathon runners during training and competition and the dearth of studies that address performance and cytokines in this population, the objective of the current study was to investigate the relationship between RE and cytokines in marathon runners.MethodsA total of 22 recreational marathon runners were examined. Using data obtained from VO2max assessments and sub-maximal tests, the following formula was applied to determine RE: Cr (mLO2·kg-1·km-1) = VO2 (mL·kg-1·h-1) × 60 ÷ speed (km·h-1).ResultsCr values shows no correlation with levels of the serum IL-1β, IL-4, IL-8, IL-10 and TNF-a 24h before, immediately after or 72h after the completion of an official marathon. However, the IL-6 level shows a significant correlation with Cr.Discussion and conclusionThe relationship between higher values of IL-6 and lower RE leads to the hypothesis of a physical under-recovery state by some athletes. Considering the stress caused by training, associated with the higher energetic cost in less economic athletes, it’s possible that the period of resting may not totally compensate for the inflammatory state.
Reading the intentions of be going to. On the subjectification of future markers
Authors: Budts Sara , Petré Peter 
Published: November 2016

AbstractThis paper provides a detailed corpus-based account of the formal and functional changes thatbe going tounderwent in Late Modern English. Despitebe going to’s popularity, such studies remain rare for this period, in which the construction’s grammaticalization went through a second phase. Our analysis shows that the first half of the eighteenth century witnessed a shift from intention to prediction, which originated in contexts with third person subjects. Reporting the intention of others generally involves a certain amount of guesswork, which eventually resulted in the creation of an additional, epistemic layer of prediction, reinforced by the gradual extension ofbe going toto express non-imminent future situations. It is argued that this shift involves an increase in subjectivity, as the emphasis gradually moved away from the grammatical subject to the speaker: what mattered was no longer the intentions of the subject, but the knowledge of the speaker about them. Attention is also drawn to parallel developments in other future markers, particularlywill. Interestingly, and in spite of significant differences, each of these went through an intermediary stage that involved past tense uses with reference to a future in the past, which was already known to the speaker.