bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence
Authors: Brown Tommy A. , Mittendorf Elizabeth A. , Hale Diane F. , Myers John W. , Peace Kaitlin M. , Jackson Doreen O. , Greene Julia M. , Vreeland Timothy J. , Clifton G. Travis , Ardavanis Alexandros , Litton Jennifer K. , Shumway Nathan M. , Symanowski J. , Murray James L. , Ponniah Sathibalan , Anastasopoulou E. A. , Pistamaltzian N. F. , Baxevanis Constantin N. , Perez Sonia A. , Papamichail Michael , Peoples George E. 
Published: April 2020

Abstract
Purpose
AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis.

Methods
In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated.

Results
456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG.

Conclusions
This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.
Systematic development of a training program for healthcare professionals to improve communication about breast cancer genetic counseling with low health literate patients
Authors: van der Giessen Jeanine A. M. , Ausems Margreet G. E. M. , van den Muijsenbergh Maria E. T. C. , van Dulmen Sandra , Fransen Mirjam P. 
Published: April 2020

AbstractThere is a disproportionate underuse of genetic testing in breast cancer patients from lower education or migrant background. Within these groups, communication about referral to genetic counseling appears challenging due to limited health literacy and cultural barriers. Our aim was to develop and evaluate a training program for healthcare professionals (breast surgeons and specialized nurses), to increase effective communication. We systematically developed a blended training program based on patients’ and healthcare professionals’ needs and preferences. Prior to the training, we assessed awareness, knowledge and self-efficacy of healthcare professionals. Acceptability and usefulness of the training program were assessed directly after the training. Healthcare professionals (n = 65) from 17 hospitals showed moderate to high awareness and knowledge about the prevalence and impact of limited health literacy. They were aware of cultural factors that influence communication. However, they did not feel confident in recognizing limited health literacy and their self-efficacy to communicate effectively with these patients was low. The training program was rated as acceptable and useful. Healthcare professionals lack confidence to effectively communicate with patients with limited health literacy or migrant background. The training program offers opportunities to improve communication about referral to breast cancer genetic counseling.
M1 But Not M0 Extracellular Vesicles Induce Polarization of RAW264.7 Macrophages Via the TLR4-NFκB Pathway In Vitro
Authors: Shi Yulong , Luo Peng , Wang Weikang , Horst Klemens , Bläsius Felix , Relja Borna , Xu Ding , Hildebrand Frank , Greven Johannes 
Published: April 2020

Abstract
In response to different stimuli (e.g., infections), naive macrophages polarize into M1 macrophages, which have the potential to secrete numerous pro-inflammatory cytokines and extracellular vesicles (EVs). EVs are important mediators of intercellular communication. Via horizontal transfer, EVs transport various molecules (e.g., proteins, DNA, and RNA) to target cells. This in vitro study elucidated that M1-EVs from macrophages induced by interferon-γ (IFN-γ) and lipopolysaccharide (LPS) 24 h (M1), but not M0-EVs from untreated macrophages (M0), shifted M0 into M1 phenotype via activating the nuclear factor-κB pathway. The characteristics of these EVs were assessed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and a western blot assay. RAW 264.7 cells were incubated with M1-EVs (experimental group) or PBS (sham group) or M0-EVs (control group) for 24 h. The viability, change of shape, and phenotype differentiation of the macrophages were identified by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and immunofluorescence staining. The TLR4-NFκB pathway of RAW264.7 macrophages was assessed by a western blot assay. M1-EVs but not M0-EVs were incorporated by the RAW264.7 cells and directly induced polarization of RAW264.7 macrophages to M1 macrophages. This polarization was demonstrated by significant upregulation of the M1 macrophage marker CD86 in the experimental group (49.93 ± 5.0%) as compared with that in the control and sham groups (1.22% and 1.46%, respectively) and significant upregulation of iNOS in the experimental group (75 ± 5.0%) as compared with that in the control and sham groups (0%). Furthermore, cell viability was higher (1.3 times) in the experimental group as compared with that in both the sham and control groups. The regulatory mechanism of M1-EVs on RAW 264.7 macrophages polarization and activation was triggered by the activation of the TLR4-NFκB signaling pathway. Based on our observations, we conclude that M1-EVs play an important role in the M1 macrophage auto-polarizing loop. These data clearly demonstrate an important role for macrophage-derived EVs in cellular differentiation. Further studies are needed to elucidate the potential of these EVs in the modulation of inflammatory stimuli.
Territorial Ironies: Deservingness as a Struggle for Migrant Legitimacy in Belgium
Authors: van Meeteren Masja , Sur Malini 
Published: April 2020

AbstractThis article ethnographically examines the everyday lives and collective activism of undocumented migrants in Belgium as they await the results of asylum appeals and regularisation applications. We show how the values emphasised by state-led migrant legalisation regimes contrast with undocumented migrants’ narratives of their own worthiness. In foregrounding deservingness as a moral and legal threshold, we argue that the Belgian nation-state responds to undocumented migrants by enforcing and implementing citizenship policies that persistently keep them on the fringes of legitimacy and recognition. The discursive constructions of ‘good citizens’ that undocumented migrants embody and make claims to in Belgium extend to and envelop the lives of undocumented migrants in Europe in general.
Dexmedetomidine had neuroprotective effects on hippocampal neuronal cells via targeting lncRNA SHNG16 mediated microRNA-10b-5p/BDNF axis
Authors: Wang Li , Liu Weihua , Zhang Yanjun , Hu Zhanfei , Guo Hao , Lv Jingshu , Du Hongyin 
Published: April 2020

AbstractDexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen–glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3′-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.
‘For good measure’: data gaps in a big data world
Authors: Giest Sarah , Samuels Annemarie 
Published: April 2020

AbstractPolicy and data scientists have paid ample attention to the amount of data being collected and the challenge for policymakers to use and utilize it. However, far less attention has been paid towards the quality and coverage of this data specifically pertaining to minority groups. The paper makes the argument that while there is seemingly more data to draw on for policymakers, the quality of the data in combination with potential known or unknown data gaps limits government’s ability to create inclusive policies. In this context, the paper defines primary, secondary, and unknown data gaps that cover scenarios of knowingly or unknowingly missing data and how that is potentially compensated through alternative measures. Based on the review of the literature from various fields and a variety of examples highlighted throughout the paper, we conclude that the big data movement combined with more sophisticated methods in recent years has opened up new opportunities for government to use existing data in different ways as well as fill data gaps through innovative techniques. Focusing specifically on the representativeness of such data, however, shows that data gaps affect the economic opportunities, social mobility, and democratic participation of marginalized groups. The big data movement in policy may thus create new forms of inequality that are harder to detect and whose impact is more difficult to predict.
Deriving Niger’s Demographic and Education Future to 2062 with Stakeholders: Which Results?
Authors: Goujon Anne , Marois Guillaume , Sabourin Patrick 
Published: April 2020

Abstract
Niger has the fastest population growth in the world while being among the least developed countries. With an average fertility above seven children per woman in the last decades, rapid population growth will continue in the medium to long term representing a planning challenge for Niger's development whose actual population is likely to double within the next two decades. At the same time, socio-economic variables whether in terms of health, wealth, and education levels are lagging behind, also relatively to many countries in sub-Saharan Africa. While both demographic and education variables occupy a central position in the government strategy, they are not necessarily linked. However, the future of Niger will largely be a reflection of its ability to meet both challenges. Within a project piloted by the Ministry of Planning and funded by the United Nations Children’s Fund, we have derived together with local experts and stakeholders narratives about the possible future of Niger. These were further translated into five scenarios with assumptions about different future paths of demographic and educational development for Niger that were used to project the population, also at sub-national level, using multi-state population projection models with the aim to inform policy. This article reports some projection results related to educational and demographic developments.
Direct hydrogenation of CO2 to dimethyl ether (DME) over hybrid catalysts containing CuO/ZrO2 as a metallic function and heteropolyacids as an acidic function
Authors: Kornas A. , Śliwa M. , Ruggiero-Mikołajczyk M. , Samson K. , Podobiński J. , Karcz R. , Duraczyńska D. , Rutkowska-Zbik D. , Grabowski R. 
Published: April 2020

AbstractDimethyl ether (DME) is considered as a substitution of diesel oil. It can be used in diesel engines because of its high cetane number (> 55). The combustion process does not generate particle matter (PM) or sulphur oxides (SOx) pollutions. One of the methods to obtain DME is direct synthesis from a CO2 and H2 mixture. On the other hand, CO2 is an attractive reagent, which is a safe and economical source of carbon. The aim of this work was to obtain DME in the direct process from the mixture CO2 and H2 in the presence of hybrid catalyst. In these catalytic the CuO/ZrO2 was selected as a metallic function. The montmorillonite K10 modified by heteropolyacids was selected as an acidic function. The catalysts were obtained by different preparation methods and contained various types of heteropolyacids. The catalysts were characterized by following methods: BET/BJH, XRD, SEM, DCS/TG, NH3-TPD and FT-IR. The direct hydrogenation of CO2 was performed in the high pressure fixed-bed flow reactor connected online with GC equipped with TCD and FID detectors. It was shown that both synthesis method of metallic function and the type of heteropolyacids have influence on the total catalytic activity of the hybrid catalyst. The acidity and thermal stability of HPAs are identified as the most important parameters having a decisive influence on the overall catalytic activity of the samples.
Autonomic architecture for fault handling in mobile robots
Authors: Doran Martin , Sterritt Roy , Wilkie George 
Published: April 2020

AbstractThis paper describes a generic autonomic architecture for use in developing systems for managing hardware faults in mobile robots. The method by which the generic architecture was developed is also described. Using autonomic principles, we focused on how to detect faults within a mobile robot and how specialized algorithms can be deployed to compensate for the faults discovered. We design the foundation of a generic architecture using the elements found in the MAPE-K and IMD architectures. We present case studies that show three different fault scenarios that can occur within the effectors, sensors and power units of a mobile robot. For each case study, we have developed algorithms for monitoring and analyzing data stored from previous tasks completed by the robot. We use the results from the case studies to create and refine a generic autonomic architecture that can be utilized for any general mobile robot setup for fault detection and fault compensation. We then describe a further case study which exercises the generic autonomic architecture in order to demonstrate its utility. Our proposal addresses fundamental challenges in operating remote mobile robots with little or no human intervention. If a fault does occur within the mobile robot during field operations, then having a self-automated strategy as part of its processes may result in the mobile robot continuing to function at a productive level. Our research has provided insights into the shortcomings of existing robot design which is also discussed.
Acoustic signal analysis of instrument–tissue interaction for minimally invasive interventions
Authors: Ostler Daniel , Seibold Matthias , Fuchtmann Jonas , Samm Nicole , Feussner Hubertus , Wilhelm Dirk , Navab Nassir 
Published: April 2020

Abstract
Purpose

Minimally invasive surgery (MIS) has become the standard for many surgical procedures as it minimizes trauma, reduces infection rates and shortens hospitalization. However, the manipulation of objects in the surgical workspace can be difficult due to the unintuitive handling of instruments and limited range of motion. Apart from the advantages of robot-assisted systems such as augmented view or improved dexterity, both robotic and MIS techniques introduce drawbacks such as limited haptic perception and their major reliance on visual perception.

Methods

In order to address the above-mentioned limitations, a perception study was conducted to investigate whether the transmission of intra-abdominal acoustic signals can potentially improve the perception during MIS. To investigate whether these acoustic signals can be used as a basis for further automated analysis, a large audio data set capturing the application of electrosurgery on different types of porcine tissue was acquired. A sliding window technique was applied to compute log-mel-spectrograms, which were fed to a pre-trained convolutional neural network for feature extraction. A fully connected layer was trained on the intermediate feature representation to classify instrument–tissue interaction.

Results

The perception study revealed that acoustic feedback has potential to improve the perception during MIS and to serve as a basis for further automated analysis. The proposed classification pipeline yielded excellent performance for four types of instrument–tissue interaction (muscle, fascia, liver and fatty tissue) and achieved top-1 accuracies of up to 89.9%. Moreover, our model is able to distinguish electrosurgical operation modes with an overall classification accuracy of 86.40%.

Conclusion

Our proof-of-principle indicates great application potential for guidance systems in MIS, such as controlled tissue resection. Supported by a pilot perception study with surgeons, we believe that utilizing audio signals as an additional information channel has great potential to improve the surgical performance and to partly compensate the loss of haptic feedback.
Learned optical flow for intra-operative tracking of the retinal fundus
Authors: Ravasio Claudio S. , Pissas Theodoros , Bloch Edward , Flores Blanca , Jalali Sepehr , Stoyanov Danail , Cardoso Jorge M. , Da Cruz Lyndon , Bergeles Christos 
Published: April 2020

AbstractPurposeSustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools.MethodsAs manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases.ResultsThe U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos.ConclusionsThe results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.
Towards better representations of carbon allocation in vegetation: a conceptual framework and mathematical tool
Authors: Ceballos-Núñez Verónika , Müller Markus , Sierra Carlos A. 
Published: April 2020

AbstractThe representation of carbon allocation (CA) in ecosystem differs tremendously among models, resulting in diverse responses of carbon cycling and storage to global change. Several studies have highlighted discrepancies between empirical observations and model predictions, attributing these differences to problems of model structure. We analyzed the mathematical representation of CA in models using concepts from dynamical systems theory; we reviewed a representative sample of models of CA in vegetation and developed a model database within the Python package bgc-md. We asked whether these representations can be generalized as a linear system, or whether a more general framework is needed to accommodate nonlinearities. Some of the vegetation systems simulated with the reviewed models have a fixed partitioning of photosynthetic products, independent of environmental forcing. Vegetation is often represented as a linear system without storage compartments. Yet, other structures with nonlinearities have also been proposed, with important consequences on the temporal trajectories of ecosystem carbon compartments. The proposed mathematical framework unifies the representation of alternative CA schemes, facilitating their classification according to mathematical properties as well as their potential temporal behaviour. It can represent complex processes in a compact form, which can potentially facilitate dialog among empiricists, theoreticians, and modellers.
ESMO 2019—personal highlights in gastrointestinal cancer
Authors: Amann A. 
Published: April 2020

SummaryThis article summarizes important highlights regarding gastrointestinal cancer at the 2019 ESMO annual meeting. The choice of the abstracts was based on a personal view with a focus on different tumor entities of the gastrointestinal tract. Precision-medicine-guided therapy for cancer entities was one of the main topics at this year’s ESMO. Furthermore, circulating tumor DNA (ctDNA) by performing liquid biopsy was again another hot topic, especially in guiding adjuvant chemotherapy in stage III colorectal cancer (CRC) patients. Finally, hope was stirred up again for immunotherapy in the indication of first-line treatment in nonresectable hepatocellular cancer (HCC). In summary, the astonishing progress in new drugs that has been made in recent years is still ongoing and will lead to better treatment for cancer patients.