bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy
Authors: Galli Filippo , Aguilera Jesus Vera , Palermo Belinda , Markovic Svetomir N. , Nisticò Paola , Signore Alberto 
Published: May 2020

AbstractTumor-infiltrating immune cells play a key role against cancer. However, malignant cells are able to evade the immune response and establish a very complex balance in which different immune subtypes may drive tumor progression, metastatization and resistance to therapy. New immunotherapeutic approaches aim at restoring the natural balance and increase immune response against cancer by different mechanisms. The complexity of these interactions and the heterogeneity of immune cell subpopulations are a real challenge when trying to develop new immunotherapeutics and evaluate or predict their efficacy in vivo. To this purpose, molecular imaging can offer non-invasive diagnostic tools like radiopharmaceuticals, contrast agents or fluorescent dyes. These agents can be useful for preclinical and clinical purposes and can overcome [18F]FDG limitations in discriminating between true-progression and pseudo-progression. This review provides a comprehensive overview of immune cells involved in microenvironment, available immunotherapies and imaging agents to highlight the importance of new therapeutic biomarkers and their in vivo evaluation to improve the management of cancer patients.
BpForms and BcForms: a toolkit for concretely describing non-canonical polymers and complexes to facilitate global biochemical networks
Authors: Lang Paul F. , Chebaro Yassmine , Zheng Xiaoyue , P. Sekar John A. , Shaikh Bilal , Natale Darren A. , Karr Jonathan R. 
Published: May 2020

AbstractNon-canonical residues, caps, crosslinks, and nicks are important to many functions of DNAs, RNAs, proteins, and complexes. However, we do not fully understand how networks of such non-canonical macromolecules generate behavior. One barrier is our limited formats for describing macromolecules. To overcome this barrier, we develop BpForms and BcForms, a toolkit for representing the primary structure of macromolecules as combinations of residues, caps, crosslinks, and nicks. The toolkit can help omics researchers perform quality control and exchange information about macromolecules, help systems biologists assemble global models of cells that encompass processes such as post-translational modification, and help bioengineers design cells.
Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
Authors: Laporte-Amargos J. , Gudiol C. , Arnan M. , Puerta-Alcalde P. , Carmona-Torre F. , Huguet M. , Albasanz-Puig A. , Parody R. , Garcia-Vidal C. , del Pozo J. L. , Batlle M. , Tebé C. , Rigo-Bonnin R. , Muñoz C. , Padullés A. , Tubau F. , Videla S. , Sureda A. , Carratalà J. 
Published: May 2020

Abstract
Background
Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN.
The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN.

Methods
A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group.
The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied.

Discussion
Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes.

Trial registration
European Clinical Trials Database: EudraCT 2018–001476-37.
ClinicalTrials.gov, ID: NCT04233996.
The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam
Authors:   on behalf of SEARCH investigators, McCabe Leanne , White Ian R. , Chau Nguyen Van Vinh , Barnes Eleanor , Pett Sarah L. , Cooke Graham S. , Walker A. Sarah 
Published: May 2020

Abstract
Background
Eliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly.

Methods
The VIETNARMS trial will factorially randomly assign patients to two drug regimens, three treatment-shortening strategies or control, and adjunctive ribavirin or no adjunctive ribavirin with shortening strategies (14 randomly assigned groups). We will use Bayesian monitoring at interim analyses to detect and stop recruitment into unsuccessful strategies, defined by more than 0.95 posterior probability that the true cure rate is less than 90% for the individual randomly assigned group (non-comparative). Final comparisons will be non-inferiority for regimens (margin 5%) and strategies (margin 10%) and superiority for adjunctive ribavirin. Here, we tested the operating characteristics of the stopping guideline for individual randomly assigned groups, planned interim analysis timings and explored power at the final analysis.

Results
A beta (4.5, 0.5) prior for the true cure rate produces less than 0.05 probability of incorrectly stopping an individual randomly assigned group with a true cure rate of more than 90%. Groups with very low cure rates (<60%) are very likely (>0.9 probability) to stop after about 25% of patients are recruited. Groups with moderately low cure rates (80%) are likely to stop (0.7 probability) before overall recruitment finishes. Interim analyses 7, 10, 13 and 18 months after recruitment commences provide good probabilities of stopping inferior individual randomly assigned groups. For an overall true cure rate of 95%, power is more than 90% to confirm non-inferiority in the regimen and strategy comparisons, regardless of the control cure rate, and to detect a 5% absolute difference in the ribavirin comparison.

Conclusions
The operating characteristics of the stopping guideline are appropriate, and interim analyses can be timed to detect individual randomly assigned groups that are highly likely to have suboptimal performance at various stages. Therefore, our design is suitable for evaluating treatment-shortening or -simplifying strategies.

Trial registration
ISRCTN registry: ISRCTN61522291. Registered on 4 October 2019.
Effects of various inhibitory substances and immobilization on ethanol production efficiency of a thermotolerant Pichia kudriavzevii
Authors: Ndubuisi Ifeanyi A. , Qin Qijian , Liao Guiyan , Wang Bin , Moneke Anene N. , Ogbonna James C. , Jin Cheng , Fang Wenxia 
Published: May 2020

Abstract
Background
Although bioethanol production has been gaining worldwide attention as an alternative to fossil fuel, ethanol productivities and yields are still limited due to the susceptibility of fermentation microorganisms to various stress and inhibitory substances. There is therefore an unmet need to search for multi-stress-tolerant organisms to improve ethanol productivity and reduce production cost, particularly when lignocellulosic hydrolysates are used as the feedstock.

Results
Here, we have characterized a previously isolated Pichia kudriavzevii LC375240 strain which is thermotolerant to high temperatures of 37 °C and 42 °C. More excitingly, growth and ethanol productivity of this strain exhibit strong tolerance to multiple stresses such as acetic acid, furfural, formic acid, H2O2 and high concentration of ethanol at 42 °C. In addition, simple immobilization of LC375240 on corncobs resulted to a more stable and higher efficient ethanol production for successive four cycles of repeated batch fermentation at 42 °C.

Conclusion
The feature of being thermotolerant and multi-stress-tolerant is unique to P. kudriavzevii LC375240 and makes it a good candidate for second-generation bioethanol fermentation as well as for investigating the molecular basis underlying the robust stress tolerance. Immobilization of P. kudriavzevii LC375240 on corncobs is another option for cheap and high ethanol productivity.
Nonlinear fractional differential equation involving two mixed fractional orders with nonlocal boundary conditions and Ulam–Hyers stability
Authors: Li Fang , Yang Wenjing , Wang Huiwen 
Published: May 2020

AbstractIn this paper, we study a nonlinear fractional differential equation involving two mixed fractional orders with nonlocal boundary conditions. By using some new techniques, we introduce a formula of solutions for above problem, which can be regarded as a novelty item. Moreover, under the weak assumptions and using Leray–Schauder degree theory, we obtain the existence result of solutions for above problem. Furthermore, we discuss the Ulam–Hyers stability of the above fractional differential equation. Three examples illustrate our results.
A learning style classification approach based on deep belief network for large-scale online education
Authors: Zhang Hao , Huang Tao , Liu Sanya , Yin Hao , Li Jia , Yang Huali , Xia Yu 
Published: May 2020

AbstractWith the rapidly growing demand for large-scale online education and the advent of big data, numerous research works have been performed to enhance learning quality in e-learning environments. Among these studies, adaptive learning has become an increasingly important issue. The traditional classification approaches analyze only the surface characteristics of students but fail to classify students accurately in terms of deep learning features. Meanwhile, these approaches are unable to analyze these high-dimensional learning behaviors in massive amounts of data. Hence, we propose a learning style classification approach based on the deep belief network (DBN) for large-scale online education to identify students’ learning styles and classify them. The first step is to build a learning style model and identify indicators of learning style based on the experiences of experts; then, relate the indicators to the different learning styles. We improve the DBN model and identify a student’s learning style by analyzing each individual’s learning style features using the improved DBN. Finally, we verify the DBN result by conducting practical experiments on an actual educational dataset. The various learning styles are determined by soliciting questionnaires from students based on the ILS theory by Felder and Soloman (1996) and the Readiness for Education At a Distance Indicator. Then, we utilized those data to train our DBNLS model. The experimental results indicate that the proposed DBNLS method has better accuracy than do the traditional approaches.
Effects of undigested protein-rich ingredients on polarised small intestinal organoid monolayers
Authors: Kar Soumya K. , van der Hee Bart , Loonen Linda M. P. , Taverne Nico , Taverne-Thiele Johanna J. , Schokker Dirkjan , Smits Mari A. , Jansman Alfons J. M. , Wells Jerry M. 
Published: May 2020

Abstract
Here, we describe the use of monolayers of intestinal epithelial cells derived from intestinal organoids and transcriptomics to investigate the direct effects of dietary protein sources on epithelial function. Mechanically dissociated 3D organoids of mouse duodenum were used to generate a polarized epithelium containing all cell types found in the tissue of origin. The organoid-derived cell monolayers were exposed to 4% (w/v) of ‘undigested (non-hydrolysed)-soluble’ fraction of protein sources used as feed ingredients [soybean meal (SBM) and casein], or alternative protein sources (spray dried plasma protein, and yellow meal worm), or controls for 6 h prior to RNA isolation and transcriptomics. All protein sources altered expression of unique biological processes in the epithelial cells. Exposure of intestinal organoids to SBM downregulated expression of retinol and retinoid metabolic processes as well as cholesterol and lipid biosynthetic pathways, consistent with the reported hypotriglyceridaemic effect of soy protein in vivo. These findings support the use of intestinal organoids as models to evaluate complex interactions between dietary ingredients and the intestinal epithelium and highlights some unique host effects of alternative protein sources in animal feed and potentially human food.

Graphical abstract
Schematic representation of the study. 3-dimensional organoids were generated from mouse duodenum (1). The organoids were subsequently dissociated into single cells (2) and grown as 2-dimensional polarised monolayers (3). Polarized monolayers of organoid cells were exposed to different protein sources [CAS, SBM, SDPP, YMW, or medium control (MC)] for 6 h (4) and further processed for imaging (5) gene expression (6), and biochemical assays (7), to investigate the effects of undigested protein sources on the duodenal epithelium.
Initial evidence on the relationship between the coronavirus pandemic and crime in the United States
Authors: Ashby Matthew P. J. 
Published: May 2020

AbstractThe COVID-19 pandemic led to substantial changes in the daily activities of millions of Americans, with many businesses and schools closed, public events cancelled and states introducing stay-at-home orders. This article used police-recorded open crime data to understand how the frequency of common types of crime changed in 16 large cities across the United States in the early months of 2020. Seasonal auto-regressive integrated moving average (SARIMA) models of crime in previous years were used to forecast the expected frequency of crime in 2020 in the absence of the pandemic. The forecasts from these models were then compared to the actual frequency of crime during the early months of the pandemic. There were no significant changes in the frequency of serious assaults in public or (contrary to the concerns of policy makers) any change to the frequency of serious assaults in residences. In some cities, there were reductions in residential burglary but little change in non-residential burglary. Thefts of motor vehicles decreased in some cities while there were diverging patterns of thefts from motor vehicles. These results are used to make suggestions for future research into the relationships between the coronavirus pandemic and different crimes.
Impact of dead time on quantitative 177Lu-SPECT (QSPECT) and kidney dosimetry during PRRT
Authors: Desy Alessandro , Bouvet Guillaume F. , Frezza Andrea , Després Philippe , Beauregard Jean-Mathieu 
Published: May 2020

Abstract
Background
Dead time may affect the accuracy of quantitative SPECT (QPSECT), and thus of dosimetry. The aim of this study was to quantify the effect of dead time on 177Lu-QSPECT and renal dosimetry following peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours.

Methods
QSPECT/CT was performed on days 1 and 3 during 564 personalized 177Lu-octreotate cycles in 166 patients. The dead-time data for each scanning time point was compiled. The impact of not correcting QSPECT for the dead time was assessed for the kidney dosimetry. This was also estimated for empiric PRRT by simulating in our cohort a regime of 7.4 GBq/cycle.

Results
The probability to observe a larger dead time increased with the injected activity. A dead-time loss greater than 5% affected 14.4% and 5.7% of QSPECT scans performed at days 1 and 3, respectively. This resulted in renal absorbed dose estimates that would have been underestimated by more than 5% in 5.7% of cycles if no dead-time correction was applied, with a maximum underestimation of 22.1%. In the simulated empiric regime, this potential dose underestimation would have been limited to 6.2%.

Conclusion
Dead-time correction improves the accuracy of dosimetry in 177Lu radionuclide therapy and is warranted in personalized PRRT.
Role of molecular biomarkers in glioma resection: a systematic review
Authors: Li Lianwang , Wang Yinyan , Li Yiming , Fang Shengyu , Jiang Tao 
Published: May 2020

AbstractNew discoveries based on genetic and epigenetic evidence have significantly expanded the understanding of diffuse gliomas. Molecular biomarkers detected in diffuse gliomas are not only potential targets for radiotherapy, chemotherapy, and immunotherapy, but are also able to guide surgical treatment. Previous studies have suggested that the optimal extent of resection of diffuse gliomas varies according to the expression of specific molecular biomarkers. However, the specific guiding role of these biomarkers in the resection of diffuse gliomas has not been systemically analyzed. This review summarizes several critical molecular biomarkers of tumorigenesis and progression in diffuse gliomas and discusses different strategies of tumor resection in the context of varying genetic expression. With ongoing study and advances in technology, molecular biomarkers will play a more important role in glioma resection and maximize the survival benefit from surgery for diffuse gliomas.
Performance and cost-benefit analysis of Isa Brown layers on different management systems
Authors: Okedere Daniel Adeolu , Ademola Peace Queen , Asiwaju Priscilla Mofifoluwa 
Published: May 2020

AbstractBackgroundFew literatures exist on the performance and cost implication of birds reared on different management system. The cost benefit analysis of rearing Isa Brown layers on three different management systems was evaluated in a 9 (9)-week feeding trial. One hundred and forty-four (144) points of lay (19 weeks old) Isa-Brown chickens were procured from a reputable farm in Osun state. The birds were placed on three (3) treatments (battery cage, deep litter, and free range) of three (3) replicates and sixteen (16) birds per replicate in a completely randomized design. Birds reared on conventional cages were arranged into three birds per cage unit. Birds on deep litter were kept on wood shavings, in which perches, laying nests, feeders, and drinkers were provided. Hens on free range management system were kept in a large area of land camped using planks and hexagonal wire mesh which was partitioned into various replicates. Sheds were provided for the birds to protect them from harsh weather conditions, and perches, laying nests, feeders, and drinkers were also provided. The birds on all the treatments (battery cage, deep litter and free range) were given the same diet, and the study period lasted for sixty-five days. The weight gain per bird, percentage weight gain, hen day production (HDP), egg mass index, and feed conversion ratio were determined. At the end of the experiment, these records were used to evaluate economic indices.ResultsThe result showed that only the feed intake and total feed intake were significantly (p< 0.05) influenced by management systems in all the parameters measured for performance. The daily feed intake, total feed intake total cost of feed consumed, quantity of egg produced per bird, revenue generated from eggs, production cost, net benefit, cost-benefit ratio, and percentage cost of production were significantly (p< 0.05) influenced by management systems. Birds kept on deep litter system recorded the highest (48.87) number of eggs produced. The cost of construction was recorded to be highest in battery cage system while construction of free range facilities was at the minimum. Revenue generated from egg sold was highest (₦1384.56) in deep litter system while free range recorded the least significant (p< 0.05) (₦1301.44) value. Total cost of producing table eggs was significantly (p< 0.05) highest (₦2251.54) in battery cage, while free range had the least (₦2074.88) cost of production. Free range birds recorded the highest (₦326.56) net benefit, while the least (₦195.24) net benefit was obtained in battery cage.ConclusionIt was therefore concluded that free range management system resulted into better profit margin and could however be adopted by small scale farmers in rural areas willing to practice backyard poultry farming.