bluuebunny/crossref_metadata_2025_split huggingface dataset:
DecoPath: A web application for decoding pathway enrichment analysis
Authors: Mubeen Sarah , Bharadhwaj Vinay Srinivas , Gadiya Yojana , Hofmann-Apitius Martin , Kodamullil Alpha Tom , Domingo-Fernández Daniel 
Published: May 2021

AbstractThe past two decades have brought a steady growth of pathway databases and pathway enrichment methods. However, the advent of pathway data has not been accompanied by an improvement with regards to interoperability across databases, thus, hampering the use of pathway knowledge from multiple databases for pathway enrichment analyses. While integrative databases have attempted to address this issue by collating pathway knowledge from multiple resources, these approaches do not account for redundant information across them. On the other hand, the majority of studies that employ pathway enrichment analyses still rely upon a single database, though the use of another resource could yield differing results, which is similarly the case when different pathway enrichment methods are employed. These shortcomings call for approaches that investigate the differences and agreements across databases and enrichment methods as their selection in the experimental design of a pathway analysis can be a crucial first step in ensuring the results of such an analysis are meaningful. Here we present DecoPath, a web application to assist in the interpretation of the results of pathway enrichment analysis. DecoPath provides an ecosystem to run pathway enrichment analysis or directly upload results and facilitate the interpretation of these results with custom visualizations that highlight the consensus and/or discrepancies at the pathway- and gene-levels. DecoPath is available at https://decopath.scai.fraunhofer.de and its source code and documentation can be found on GitHub at https://github.com/DecoPath/DecoPath.
Controlling pallidal oscillations in real-time in Parkinson’s disease using evoked interference deep brain stimulation (eiDBS): proof of concept in the human
Authors: Escobar Sanabria David , Aman Joshua E. , Zapata Amaya Valentina , Johnson Luke A. , Farooqi Hafsa , Wang Jing , Hill Meghan , Patriat Remi , Sovell-Brown Kelly , Molnar Gregory F. , Darrow David , McGovern Robert , Cooper Scott E. , Harel Noam , MacKinnon Colum D. , Park Michael C. , Vitek Jerrold L. 
Published: May 2021

SummaryApproaches to control basal ganglia neural activity in real-time are needed to clarify the causal role of 8-35 Hz (“beta band”) oscillatory dynamics in the manifestation of Parkinson’s disease (PD) motor signs. Here, we show that resonant beta oscillations evoked by electrical pulse with precise amplitude and timing can be used to predictably suppress or amplify spontaneous beta band activity in the internal segment of the globus pallidus (GPi) in the human. Using this approach, referred to as closed-loop evoked interference deep brain stimulation (eiDBS), we could suppress or amplify frequencyspecific (16-22 Hz) neural activity in a PD patient. Our results highlight the utility of eiDBS to characterize the role of oscillatory dynamics in PD and other brain conditions, and to develop personalized neuromodulation systems.
Redundant enhancers in the iab-5 domain cooperatively activate Abd-B in the A5 and A6 abdominal segments of Drosophila
Authors: Postika Nikolay , Schedl Paul , Georgiev Pavel , Kyrchanova Olga 
Published: May 2021

AbstractThe homeotic Abdominal-B (Abd-B) gene belongs to Bithorax complex and is regulated by four regulatory domains named iab-5, iab-6, iab-7 and iab-8, each of which is thought to be responsible for directing the expression of Abd-B in one of the abdominal segments from A5 to A8. It is assumed that male specific features of the adult cuticle in A5 is solely dependent on regulatory elements located in iab-5, while the regulatory elements in the iab-6 are both necessary and sufficient for the proper differentiation of the A6 cuticle. Unexpectedly, we found that this long held assumption is not correct. Instead, redundant tissue-specific enhancers located in the iab-5 domain are required for the proper activation of Abd-B not only in A5 but also in A6. Our study of deletions shows that the iab-5 initiator is essential for the functioning of the iab-5 enhancers in A5, as well as for the correct differentiation of A6. This requirement is circumvented by deletions that remove the initiator and most of the iab-5 regulatory domain sequences. While the remaining iab-5 enhancers are inactive in A5, they are activated in A6 and contribute to the differentiation of this segment. In this case, Abd-B stimulation by the iab-5 enhancers in A6 depends on the initiators in the iab-4 and iab-6 domains.Summary StatementIn Drosophila, the segmental-specific expression of the homeotic gene Abdominal-B in the abdominal segments is regulated by autonomous regulatory domains. We demonstrated cooperation between these domains in activation of Abdominal-B.
Reuse of an insect wing venation gene-regulatory subnetwork in patterning the eyespot rings of butterflies
Authors: Banerjee Tirtha Das , Monteiro Antónia 
Published: May 2021

AbstractNovel organismal traits might reuse ancestral gene-regulatory networks (GRNs) in their development, but data supporting this mechanism are still sparse. Here we show the reuse of an ancestral insect venation gene regulatory subnetwork patterning the sharp and distinct rings of color in butterfly eyespots. Using laser microdissection followed by RNA-Seq we first obtained transcriptional profiles of the anterior and posterior compartment of larval wings, and eyespot and adjacent control tissue in pupal wings ofBicyclus anynanabutterflies. We identified key venation patterning genes such asMothers against dpp 6 (Mad6), thickveins, Optix, spalt, optomotor-blind (omb), aristaless, cubitus interruptus,andpatcheddifferentially expressed (DE) across compartments, and a sub-set of these genes also DE across eyespot and non-eyespot samples. Fluorescentin-situhybridization (HCR3.0) on the jointly DE genesMad6, Optix,andspalt, as well asdppshowed clear eyespot-center, eyespot-rings, and compartment-specific expression. Knocking outdppresulted in an individual with venation defects and loss of eyespots, whereas knockouts ofOptixandspaltresulted in the loss of orange scales and black scales, respectively. Furthermore, using CRISPR-Cas9 followed by immunostainings, we showed that Spalt repressesOptixin the central region of the eyespot, limitingOptixexpression to a more peripheral ring, which parallels the regulatory interaction found in venation patterning in the anterior compartment of fly larval wings. These network similarities suggest that part of the venation GRN was co-opted to aid in the differentiation of the eyespot rings.One-sentence summaryWe showed the reuse of an ancestral insect wing venation GRN in patterning a novel complex trait in butterflies.
Dynamic FRET-FLIM based screens of signal transduction pathways: a feasibility study
Authors: Harkes Rolf , Kukk Olga , Mukherjee Sravasti , Klarenbeek Jeffrey , van den Broek Bram , Jalink Kees 
Published: May 2021

AbstractFluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative method to screen for protein-protein interactions and frequently used to record the outcome of signal transduction events. With new highly sensitive and photon efficient FLIM instrumentation, the technique also becomes attractive to screen, with high temporal resolution, for fast changes in Förster Resonance Energy Transfer (FRET), such as those occurring upon activation of cell signaling.We studied the effects of siRNA-mediated individual knockdown of an extensive set of 22 different phosphodiesterases (PDEs) on baseline levels and agonist-induced changes of the second messenger cAMP. Using HeLa cells stably expressing our FRET-FLIM sensor we imaged many hundreds of cells at 5 second intervals for each condition. Following segmentation of cells by the deep-learning implementation Cellpose, FLIM time traces were calculated and fitted for dynamic analysis with custom-made Python scripts. Taking advantage of the quantitative FLIM data, we found very limited effects of PDE knockdown on baseline and agonist-induced peak levels of cAMP. However, cAMP breakdown in the decay phase was significantly slower when PDE3A and, to a lesser amount, PDE10A were knocked down, identifying these isoforms as dominant in HeLa cells.In conclusion, we present a robust platform that combines photon-efficient FLIM instrumentation with systematic gene knockdown and an automated open-source analysis pipeline. Our quantitative platform provides detailed kinetic analysis of cellular signals in individual cells with unprecedented throughput.
Prevalent and Dynamic Binding of the Cell Cycle Checkpoint Kinase Rad53 to Gene Promoters
Authors: Sheu Yi-Jun , Kawaguchi Risa Karakida , Gillis Jesse , Stillman Bruce 
Published: May 2021

AbstractReplication of the genome must be coordinated with gene transcription and cellular metabolism, especially following replication stress in the presence of limiting deoxyribonucleotides. TheS. cerevisiaeRad53 (CHEK2 in mammals) checkpoint kinase plays a major role in cellular responses to DNA replication stress. Cell cycle regulated, genome-wide binding of Rad53 to chromatin was examined. Under replication stress, the kinase bound to sites of active DNA replication initiation and fork progression, but unexpectedly to the promoters of about 20% of genes encoding proteins involved in multiple cellular functions. Rad53 promoter binding correlated with changes in expression of a subset of genes. Rad53 promoter binding to certain genes was influenced by sequence-specific transcription factors and less by checkpoint signaling. However, in checkpoint mutants, untimely activation of late-replicating origins reduces the transcription of nearby genes, with concomitant localization of Rad53 to their gene bodies. We suggest that the Rad53 checkpoint kinase coordinates genome-wide replication and transcription under replication stress conditions.
Inhibitors and facilitators of corporate real estate dynamic alignment
Authors: Cooke Howard , Appel-Meulenbroek Rianne , Arentze Theo 
Published: May 2021

PurposeThis paper aims to identify the importance of individual variables in the corporate real estate (CRE) decision-making process.Design/methodology/approachNine experts received a posed scenario of a changed business strategy requiring a CRE reduction in individual interviews. Based on their suggested response, a decision network was modelled for each expert using the causal network elicitation technique, incorporating the utilities for decision variables and importance weights for attributes and benefits. The decision model offers a graphical representation of decision-benefit links for the decisions CRE managers make in such a period of decline.FindingsPerceived facilitators of CRE dynamic alignment were identified by calculating lift ratios on their perceived importance of the attributes they mentioned during the interviews as nodes in the network that link decisions to benefits. Facilitators included CRE metrics and workplace strategy, while capital expenditure and landlords inhibit alignment processes. The research provides more granular insight into the variables used in CRE decision-making and the factors that facilitate or inhibit the dynamic alignment process.Research limitations/implicationsThe research set a specific scenario for the experts to consider. That could be regarded as small but there was clear evidence of saturation of expert knowledge. Additional face-to-face interviews with the experts may have generated further details on the thought processes of the experts.Practical implicationsThe research provides more granular insight into the variables used in CRE decision-making and the factors that facilitate or inhibit the dynamic alignment process. Thereby providing CRE decision-makers with key elements for a decision model.Originality/valueThe research technique, causal network elicitation technique, uses semi-structured interviews to create decision networks, which is a technique that has not been widely applied to CRE research. The research provides a granular view of what are important inhibitors or facilitators of dynamic alignment of CRE to business strategy.
Piloting an adaptive skills virtual reality intervention for adults with autism: findings from user-centered formative design and evaluation
Authors: Schmidt Matthew M. , Glaser Noah 
Published: May 2021

Purpose
The purpose of this paper is to present evaluation findings from a proof-of-concept virtual reality adaptive skills intervention called Virtuoso, designed for adults with autism spectrum disorders.

Design/methodology/approach
A user-centric usage test was conducted to investigate the acceptability, feasibility, ease-of-use and relevance of Virtuoso to the unique needs of participants, as well as the nature of participants’ user experiences. Findings are presented from the perspectives of expert testers and participant testers with autism.

Findings
This paper offers findings that suggest Virtuoso is feasible and relevant to the unique needs of the target population, and that user experience was largely positive. Anecdotal evidence of skills transfer is also discussed.

Research limitations/implications
The research was conducted in limited settings and with a small number of participants. Multiple VR hardware systems were used, and some experienced instability. This could be accounted for in future research by deploying across multiple settings and with a larger number of participants. Some evidence of cybersickness was observed. Future research must carefully consider the trade-offs between VR-based training and cybersickness for this vulnerable population.

Originality/value
This paper reports on cutting-edge design and development in areas that are under-represented and poorly understood in the literature on virtual reality for individuals with autism.
Dark photon production via $$\gamma \gamma \rightarrow \gamma A'$$
Authors: Wong Xiaorui , Huang Yongsheng 
Published: May 2021

AbstractThe dark photon is a new gauge boson which arises from an extra $$U'(1)$$

U
′

(
1
)

gauge symmetry. In this paper, a novel dark photon production mechanism based on MeV-scale $$\gamma $$
γ
–$$\gamma $$
γ
collider is considered: $$\gamma \gamma \rightarrow \gamma A'$$

γ
γ
→
γ

A
′

. With the aid of PACKAGE-X, differential cross section of $$\gamma \gamma \rightarrow \gamma A'$$

γ
γ
→
γ

A
′

is obtained, as a function of the kinetic mixing parameter $$\varepsilon $$
ε
and dark photon mass $$m_{A'}$$

m

A
′

. Taking the light-by-light scattering as background, the constraints on the dark photon parameter space for different time intervals in a MeV-scale $$\gamma $$
γ
–$$\gamma $$
γ
collider are also given.
The effect of nano-hydroxyapatite/chitosan scaffolds on rat calvarial defects for bone regeneration
Authors: Chatzipetros Emmanouil , Damaskos Spyros , Tosios Konstantinos I. , Christopoulos Panos , Donta Catherine , Kalogirou Eleni-Marina , Yfanti Zafeiroula , Tsiourvas Dimitris , Papavasiliou Aggeliki , Tsiklakis Kostas 
Published: May 2021

Abstract
Background
This study aims at determining the biological effect of 75/25 w/w nano-hydroxyapatite/chitosan (nHAp/CS) scaffolds on bone regeneration, in terms of fraction of bone regeneration (FBR), total number of osteocytes (Ost), and osteocyte cell density (CD), as well as its biodegradability.

Methods
Two critical-size defects (CSDs) were bilaterally trephined in the parietal bone of 36 adult Sprague-Dawley rats (18 males and 18 females); the left remained empty (group A), while the right CSD was filled with nHAp/CS scaffold (group B). Two female rats died postoperatively. Twelve, 11, and 11 rats were euthanized at 2, 4, and 8 weeks post-surgery, respectively. Subsequently, 34 specimens were resected containing both CSDs. Histological and histomorphometric analyses were performed to determine the FBR, calculated as [the sum of areas of newly formed bone in lateral and central regions of interest (ROIs)]/area of the original defect, as well as the Ost and the CD (Ost/mm2) in each ROI of both groups (A and B). Moreover, biodegradability of the nHAp/CS scaffolds was estimated via the surface area of the biomaterial (BmA) in the 2nd, 4th, and 8th week post-surgery.

Results
The FBR of group B increased significantly from 2nd to 8th week compared to group A (P = 0.009). Both the mean CD and the mean Ost values of group B increased compared to group A (P = 0.004 and P < 0.05 respectively). Moreover, the mean value of BmA decreased from 2nd to 8th week (P = 0.001).

Conclusions
Based on histological and histomorphometric results, we support that 75/25 w/w nHAp/CS scaffolds provide an effective space for new bone formation.
Science, Business, and Policy: A long-term reflection on multidisciplinary work-based learning in a master’s track for societal integration of Science
Authors: Grooters Saskia , Zaal Emma , Gerkema Menno 
Published: May 2021

A strong theoretical approach with a specific focus on disciplinary research characterizes the common science master’s education in the Netherlands. However, a work-based learning (WBL) approach may as well be expedient and suitable for science education at master’s level. In this paper, a case study is presented of a WBL-program designed for an academic setting: the one year Science, Business and Policy (SBP) master’s track, offered at the Faculty of Science and Engineering of the University of Groningen. The paper describes the design and curriculum of the track, including its underlying theoretical framework, courses, multidisciplinary projects and work placements. Based on the SBP-track’s design we identified six possible indicators of a successful elaboration of an academic WBL-program: the SBP-track 1) is designed in response to the Bologna process; 2) is offered fully within the curriculum of a master’s program of a research university; 3) requires a sufficient academic level and disciplinary knowledge at entrée; 4) follows an educational project approach; 5) focuses on the integration and implementation of knowledge, and; 6) applies learning objectives that are specifically formulated to match the WBL educational method. A directed content analysis of SBP work placements revealed an increase in the number of SBP-students between 2003 and 2019, with an overrepresentation of life science students, as well as a large variety of real-case problems addressed for both business and policy organisations diverse in sector, size and region. Students’ grades showed a positive correlation between the initial theoretical preparation and the report made during the work placement. In conclusion, the societal interpretation of the Bologna process has been implemented successfully with SBP, by combining academic learning with gaining professional experience using a WBL-approach.
Received: 03 December 2020Accepted: 09 April 2021
The future challenges of scientific and technical higher education
Authors: Cesco Stefano , Zara Vincenzo , De Toni Alberto F. , Lugli Paolo , Evans Alexander , Orzes Guido 
Published: May 2021

The world is experiencing significant changes, including exponential growth of the global population, global warming and climate change, biodiversity loss, international migration, digitalization, smart agriculture/farming, synthetic biology, and most recently a global human health pandemic. These trends pose a set of relevant challenges for the training of new graduates as well as for the re-skilling of current workers through lifelong learning programs. Our paper seeks to answer two research questions: (1) are current study programs suitable to prepare students for their professional future and (2) are study programs adequate to deliver the needs of current and new generations of students? We analyzed the professional figures and the skills required by the job market, as well as the number of students enrolled in technical-scientific HE study programs in Europe. We discuss the needs of future students considering how the teaching tools and methods enabled by digitalization might contribute to increasing the effectiveness of training these students. Finally, we shed light on the different types of HE study programs that can meet the educational challenges of the future.
Received: 23 June 2020Accepted: 04 May 2021
CARCINOMA METAPLÁSICO DE MAMA EM PACIENTE JOVEM: UM RELATO DE CASO
Authors: Damasceno Matheus Fávero , Soares Alice Assumpção , Delgado Carolina Silva , Paiva Patricia Fraga , Assis Emilio Pereira 
Published: May 2021

RESUMO
CONTEXTUALIZAÇÃO: O câncer de mama é a 2ª neoplasia mais comum entre as mulheres no Brasil e no mundo. Essa doença, relativamente rara antes dos 35 anos possui características altamente heterogêneas, patologia específica e comportamento biológico distinto. Dentre os Subtipos, o Carcinoma Mamário Metaplásico possui uma incidência de apenas 0,2-5% nos casos de câncer de mama. O objetivo desse estudo é relatar, a partir de uma comparação e revisão de literatura, o caso de uma paciente portadora do carcinoma mamário metaplásico, abaixo de 40 anos, pela raridade do tipo histológico e de seu comportamento agressivo. DESCRIÇÃO DA EXPERIÊNCIA: A paciente inicialmente aos 28 anos apresentou o Papiloma Atípico e 2 anos depois desenvolveu o Carcinoma Mamário Metaplásioco, além de múltiplos nódulos metastáticos pulmonares, comum desse subtipo, e hepáticos. CONSIDERAÇÕES FINAIS: Deve-se destacar que é difícil extrair conclusões definitivas quanto ao prognóstico e tratamento destas lesões, uma vez que elas são muito infrequentes na maior parte de série de casos publicados.
Palavras-chave: Carcinoma Mamário Metaplásico, Carcinoma Mamário, Neoplasia Mamária Malígna, Câncer de Mama.
ABSTRACT
CONTEXT: The breast cancer is the 2nd most common neoplasia among women in Brasil and around the world. This disease, relatively rare before the age of 35 years, has highly heterogeneous characteristics, especific pathology and distinct biological behavior. Among the subtypes, the Metaplastic Breast Carcinoma has an incidence of only 0,2-5% between the breast cancer cases. The purpose of this study is to report, from a comparison and literature review, the case of a patient with Metaplastic Breast Carcinoma, below 40 yers old, due to the rarity of the histological type and its aggressive behavior. EXPERIENCE DESCRIPTION: The patient, inicially 28 years old presented the Atipic Papilloma and 2 years later developed the Metaplastic Breast Carcinoma, in adittion to multiple metastatic pulmonary nodes, common of the type, and hepatic. FINAL CONSIDERATIONS: It should be noted that it is difficult to draw definitive conclusions about the prognosis and treatment of these lesions, since they are very infrequent in most of the series of published cases.
Keywords: Metaplastic Breast Carcinoma, Breast Carcinoma, Malign Breast Neoplasia, Breast Cancer.