bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of nuclear export restores nuclear localization and residual tumor suppressor function of truncated SMARCB1/INI1 protein in a molecular subset of atypical teratoid/rhabdoid tumors
Authors: Pathak Rajiv , Zin Francesca , Thomas Christian , Bens Susanne , Gayden Tenzin , Karamchandani Jason , Dudley Roy W. , Nemes Karolina , Johann Pascal D. , Oyen Florian , Kordes Uwe , Jabado Nada , Siebert Reiner , Paulus Werner , Kool Marcel , Frühwald Michael C. , Albrecht Steffen , Kalpana Ganjam V. , Hasselblatt Martin 
Published: May 2021

AbstractLoss of nuclear SMARCB1 (INI1/hSNF5/BAF47) protein expression due to biallelic mutations of the SMARCB1 tumor suppressor gene is a hallmark of atypical teratoid/rhabdoid tumors (ATRT), but the presence of cytoplasmic SMARCB1 protein in these tumors has not yet been described. In a series of 102 primary ATRT, distinct cytoplasmic SMARCB1 staining on immunohistochemistry was encountered in 19 cases (19%) and was highly over-represented in cases showing pathogenic sequence variants leading to truncation or mutation of the C-terminal part of SMARCB1 (15/19 vs. 4/83; Chi-square: 56.04, p = 1.0E−10) and, related to this, in tumors of the molecular subgroup ATRT-TYR (16/36 vs. 3/66; Chi-square: 24.47, p = 7.6E−7). Previous reports have indicated that while SMARCB1 lacks a bona fide nuclear localization signal, it harbors a masked nuclear export signal (NES) and that truncation of the C-terminal region results in unmasking of this NES leading to cytoplasmic localization. To determine if cytoplasmic localization found in ATRT is due to unmasking of NES, we generated GFP fusions of one of the SMARCB1 truncating mutations (p.Q318X) found in the tumors along with a p.L266A mutation, which was shown to disrupt the interaction of SMARCB1-NES with exportin-1. We found that while the GFP-SMARCB1(Q318X) mutant localized to the cytoplasm, the double mutant GFP-SMARCB1(Q318X;L266A) localized to the nucleus, confirming NES requirement for cytoplasmic localization. Furthermore, cytoplasmic SMARCB1(Q318X) was unable to cause senescence as determined by morphological observations and by senescence-associated β-galactosidase assay, while nuclear SMARCB1(Q318X;L266A) mutant regained this function. Selinexor, a selective exportin-1 inhibitor, was effective in inhibiting the nuclear export of SMARCB1(Q318X) and caused rapid cell death in rhabdoid tumor cells. In conclusion, inhibition of nuclear export restores nuclear localization and residual tumor suppressor function of truncated SMARCB1. Therapies aimed at preventing nuclear export of mutant SMARCB1 protein may represent a promising targeted therapy in ATRT harboring truncating C-terminal SMARCB1 mutations.
Noninvasive Measurement of Pulmonary Function in Experimental Mouse Models of Airway Disease
Authors: Glaab Thomas , Braun Armin 
Published: May 2021

AbstractMouse models have become an indispensable tool in translational research of human airway disease and have provided much of our understanding of the pathogenesis of airway disease such as asthma. In these models the ability to assess pulmonary function and particularly airway responsiveness is critically important. Existing methods for testing pulmonary function in mice in vivo include noninvasive and invasive technologies. Noninvasive head-out body plethysmography is a well-established and widely accepted technique which has been proven as a reliable method to measure lung function on repeated occasions in intact, conscious mice. We have performed several validation studies in allergic mice to compare the parameter midexpiratory flow (EF50) as a noninvasive marker of airflow limitation with invasively measured gold standard parameters of lung mechanics. The results of these studies showed a good agreement of EF50 with the invasive assessment of lung resistance and dynamic compliance with a somewhat lower sensitivity of EF50. The measurement of EF50 together with basic respiratory parameters is particularly appropriate for simple and repeatable screening of pulmonary function in large numbers of mice or if noninvasive measurement without use of anesthesia is required. Beyond known applications, head-out body plethysmography also provides a much-needed high-throughput screening tool to gain insights into the impact and kinetics of respiratory infections such as SARS-COV-2 on lung physiology in laboratory mice.
Different disc characteristics between young elite skiers with diverse training histories revealed with a novel quantitative magnetic resonance imaging method
Authors: Lagerstrand K. , Baranto A. , Hebelka H. 
Published: May 2021

Abstract
Purpose
To evaluate if there are differences in thoraco-lumbar disc characteristics between elite skiers and non-athletic controls as well as between different types of elite skiers, with diverse training histories, using a novel quantitative MRI method.

Methods
The thoraco-lumbar spine of 58 elite skiers (age = 18.2 ± 1.1 years, 30 males) and 26 normally active controls (age = 16.4 ± 0.6 years, 9 males) was examined using T2w-MRI. Disc characteristics were compared quantitatively between groups using histogram and regional image analyses to determine delta peak and T2-values in five sub-regions.

Results
A statistical difference in the delta peak value was found between skiers and controls (p <0.001), reflecting higher degree of disc degeneration. The histogram analysis also revealed that the type of training determines where and to what extent the changes occur. Alpine skiers displayed lumbar changes, while mogul skiers displayed changes also in the thoracic spine. Alpine skiers with diverse training dose differed in delta peak value (p = 0.005), where skiers with highest training dose displayed less changes. Regional T2-value differences were found in skiers with divergent training histories (p <0.05), reflecting differences in disc degeneration patterns, foremost within the dorsal annulus.

Conclusion
Differences in quantitative disc characteristics were found not only between elite skiers and non-athletic controls but also between subgroups of elite skiers with diverse training histories. The differences in the disc measures, reflecting tissue degradation, are likely related to type and intensity of the physical training. Future studies are encouraged to explore the relation between disc functionality, training history and pain to establish adequate prevention and rehabilitation programs.
The C-BIG Repository: an Institution-Level Open Science Platform
Authors: Das Samir , Abou-Haidar Rida , Rabalais Henri , Sun Sonia Denise Lai Wing , Rosli Zaliqa , Chatpar Krishna , Boivin Marie-Noëlle , Tabatabaei Mahdieh , Rogers Christine , Legault Melanie , Lo Derek , Degroot Clotilde , Dagher Alain , Dyke Stephanie O. M. , Durcan Thomas M. , Seyller Annabel , Doyon Julien , Poupon Viviane , Fon Edward A. , Genge Angela , Rouleau Guy A. , Karamchandani Jason , Evans Alan C. 
Published: May 2021

AbstractIn January 2016, the Montreal Neurological Institute-Hospital (The Neuro) declared itself an Open Science organization. This vision extends beyond efforts by individual scientists seeking to release individual datasets, software tools, or building platforms that provide for the free dissemination of such information. It involves multiple stakeholders and an infrastructure that considers governance, ethics, computational resourcing, physical design, workflows, training, education, and intra-institutional reporting structures. The C-BIG repository was built in response as The Neuro’s institutional biospecimen and clinical data repository, and collects biospecimens as well as clinical, imaging, and genetic data from patients with neurological disease and healthy controls. It is aimed at helping scientific investigators, in both academia and industry, advance our understanding of neurological diseases and accelerate the development of treatments. As many neurological diseases are quite rare, they present several challenges to researchers due to their small patient populations. Overcoming these challenges required the aggregation of datasets from various projects and locations. The C-BIG repository achieves this goal and stands as a scalable working model for institutions to collect, track, curate, archive, and disseminate multimodal data from patients. In November 2020, a Registered Access layer was made available to the wider research community at https://cbigr-open.loris.ca, and in May 2021 fully open data will be released to complement the Registered Access data. This article outlines many of the aspects of The Neuro’s transition to Open Science by describing the data to be released, C-BIG’s full capabilities, and the design aspects that were implemented for effective data sharing.
INSM1 Expression in Breast Neoplasms with Neuroedocrine Features
Authors: Metovic Jasna , Castellano Isabella , Marinelli Eleonora , Osella-Abate Simona , Sapino Anna , Cassoni Paola , Papotti Mauro 
Published: May 2021

AbstractAccording to the 2019 WHO classification of breast tumors, neuroendocrine neoplasms (NENs) are classified into well-differentiated NE tumors (NET) and poorly differentiated NE carcinomas (NEC), while other breast cancers (BCs) of special and no special type with neuroendocrine (NE) features are not incorporated in this scheme anymore. We aimed to assess whether INSM1, a novel NE marker, could have a role in breast NEN subtyping. We selected 63 BCs operated from 2003 to 2018, classified as BCs with NE features, with available clinico-pathological data. Following 2019 WHO criteria, this cohort was reclassified into 37 NETs/NECs, the remaining 26 tumors representing solid-papillary (7), mucinous (7), and mixed type (12) carcinomas with NE differentiation. Chromogranin A (CGA) and synaptophysin (SYN) immunostains were reviewed, and INSM1 was tested by immunohistochemistry. Thirty CGA- and SYN-negative no special type BCs served as negative control. INSM1 was expressed in 52/63 cases of the whole cohort (82.54%). INSM1 positive and negative cases had no significantly different clinico-pathological characteristics. INSM1 expression was not significantly different between the newly reclassified NET/NEC group and other BCs with NE features. No immunoexpression was observed in control BCs. The sensitivity and specificity of INSM1 for the NE phenotype was 82.5% and 100%, respectively, compared to 61.9% and 100% for CGA, and 95.2 and 100% for SYN. In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation.
Effects of Proactive Behavior on Within-Day Changes in Occupational Well-Being: the Role of Organizational Tenure and Emotion Regulation Skills
Authors: Bohlmann Clarissa , Rudolph Cort W. , Zacher Hannes 
Published: May 2021

AbstractResearch has recently started to examine relationships between proactive behavior and employee well-being. Investigating these relationships is important to understand the effects of proactive behavior at work, and whether proactive behavior leads to an increase or a decrease in well-being. In this daily-diary study, we investigated effects of proactive behavior on within-day changes in four indicators of occupational well-being (i.e., activated positive and negative affect, emotional work engagement and fatigue). Moreover, based on the meta-concept of wise proactivity, which suggests that proactive behavior may lead to either favorable or unfavorable consequences depending on certain boundary conditions, we examined organizational tenure and emotion regulation skills as moderators of these effects. In total,N = 71 employees participated in a daily-diary study with two measurements per day for ten consecutive working days. Results showed that emotion regulation skills interacted with proactive behavior to predict within-day changes in emotional work fatigue, such that the effect of proactive behavior on emotional work fatigue was only positive for employees with low (vs. high) emotion regulation skills. Supplementary analyses examining reverse effects of occupational well-being on proactive behavior showed that organizational tenure interacted with activated positive and negative affect in predicting within-day changes in proactive behavior. For employees with lower (vs. higher) organizational tenure, both activated positive and negative affect were negatively associated with proactive behavior. Overall, our findings contribute to the growing body of research on proactive behavior and well-being by demonstrating reciprocal and conditional day-level relationships among these variables.
Survey paper: achievements and perspectives of community resilience approaches to societal systems
Authors: Toyoda Yusuke 
Published: May 2021

AbstractThe term resilience has become a buzzword with a multitude of definitions, and several studies have exerted efforts in conceptualizing it. For further academic progress, discussions on community resilience need to shift from conceptualization to operationalization. In this context, I aim to synthesize academic contributions and provide future perspectives of studies on community resilience approaches, focusing on societal systems. First, I demonstrate the general trend of community resilience research, which leads to a general analytical framework for these studies. Next, I present the results of a survey of influential studies based on this framework and discuss recent achievements in community resilience in relation to the following six elements: social, information, competence, economic, spatial, and natural. From the survey results, I suggest two perspectives: (1) the harmonization of gears for resilience and community resilience sub-elements, including equitable resilience, and (2) inactive resident pursuits of roles in community resilience. Finally, I show the potential contributions of regional science to this topic highlighting its strengths in interdisciplinary approaches based on spatial and temporal scales.
Climate-induced flood inundation for the Arial Khan River of Bangladesh using open-source SWAT and HEC-RAS model for RCP8.5-SSP5 scenario
Authors: Roy Binata , Khan Md. Sabbir Mostafa , Islam A. K. M. Saiful , Mohammed Khaled , Khan Md. Jamal Uddin 
Published: May 2021

AbstractBangladesh is one of the largest flood-prone deltas of the GBM (Ganges–Brahmaputra–Meghna) basins, and recently, it is categorized as the 7th worst climate-affected country in the world. Future climate change along with economic development, urbanization, and increase in population may worsen this situation manifolds. To cope with future flood situations and lessen probable flood losses, it is essential to develop flood maps of the major flood-prone rivers of Bangladesh considering climate change scenarios. In this study, the flood inundation of the Arial Khan River and its floodplain has been assessed for the predicted climate change scenario of RCP 8.5 (Representative Concentration Pathway 8.5) using open-source mathematical models. A calibrated and validated hydrologic model of GBM basins in SWAT (Soil and Water Assessment Tool) model has been used to estimate the future flow magnitudes at Bahadurabad Transit (Brahmaputra River) and Hardinge Bridge (Ganges River) using extreme emission scenario RCP 8.5. Using the flow magnitude of these two stations as the upstream boundaries, an HEC-RAS 1D model has been set up for the Brahmaputra, Ganges, and Padma rivers for generating future flow magnitude at the offtake of the Arial Khan River. Later, an HEC-RAS 1D-2D coupled model is set up for the Arial Khan River floodplain and flood maps are prepared considering flood depth, duration, and inundation extent. The flood assessment for different projections of RCP 8.5 shows that there is an increasing trend of flood in terms of depth, duration, and inundation from the 2020s to the 2080s. Hence, the floodplain becomes more hazardous by the end of this century. The climate change impact on the projected population for the RCP 8.5 scenario is assessed under SSP5 (Shared Socioeconomic Pathways 5) which indicates that the total flood-affected population will be nearly twice in the 2080s compared to the 2020s. So, future climate change is going to have a dreadful effect on the flood situation of the Arial Khan River floodplain.
Distributed Intelligence in the Internet of Things: Challenges and Opportunities
Authors: Alsboui Tariq , Qin Yongrui , Hill Richard , Al-Aqrabi Hussain 
Published: May 2021

AbstractWidespread adoption of smart IoT devices is accelerating research for new techniques to make IoT applications secure, scalable, energy-efficient, and capable of working in mission-critical use cases, which require an ability to function offline. In this context, the novel combination of distributed ledger technology (DLT) and distributed intelligence (DI) is seen as a practical route towards the decentralisation of IoT architectures. This paper surveys DI techniques in IoT and commences by briefly explaining the need for DI, by proposing a comprehensive taxonomy of DI in IoT. This taxonomy is then used to review existing techniques and to investigate current challenges that require careful attention and consideration. Based on the taxonomy, IoT DI techniques can be classified into five categories based on the factors that support distributed functionality and data acquisition: cloud-computing, mist-computing, distributed-ledger-technology, service-oriented-computing and hybrid. Existing techniques are compared and categorized mainly based on related challenges, and the level of intelligence supported. We evaluate more than thirty current research efforts in this area. We define many significant functionalities that should be supported by DI frameworks and solutions. Our work assists system architects and developers to select the correct low-level communication techniques in an integrated IoT-to-DLT-to-cloud system architecture. The benefits and shortcomings of different DI approaches are presented, which will inspire future work into automatic hybridization and adaptation of DI mechanisms. Finally, open research issues for distributed intelligence in IoT are discussed.
Innovation Pathways in the NHS: An Introductory Review
Authors: Arora Anmol , Wright Andrew , Cheng Tsz Kin Mark , Khwaja Zahra , Seah Matthew 
Published: May 2021

AbstractHealthcare as an industry is recognised as one of the most innovative. Despite heavy regulation, there is substantial scope for new technologies and care models to not only boost patient outcomes but to do so at reduced cost to healthcare systems and consumers. Promoting innovation within national health systems such as the National Health Service (NHS) in the United Kingdom (UK) has been set as a key target for health care professionals and policy makers. However, while the UK has a world-class biomedical research industry, several reports in the last twenty years have highlighted the difficulties faced by the NHS in encouraging and adopting innovations, with the journey from idea to implementation of health technology often taking years and being very expensive, with a high failure rate. This has led to the establishment of several innovation pathways within and around the NHS, to encourage the invention, development and implementation of cost-effective technologies that improve health care delivery. These pathways span local, regional and national health infrastructure. They operate at different stages of the innovation pipeline, with their scope and work defined by location, technology area or industry sector, based on the specific problem identified when they were set up. In this introductory review, we outline each of the major innovation pathways operating at local, regional and national levels across the NHS, including their history, governance, operating procedures and areas of expertise. The extent to which innovation pathways address current challenges faced by innovators is discussed, as well as areas for improvement and future study.
Using data to make the case for program resources and sustainability: the BEST action inventory case study
Authors: Rojewski Julie M. W. , Ayala-Lopez Nadia , Nguyen Sean , Watts Stephanie W. 
Published: May 2021

AbstractCareer development programs are a valuable part of any student’s experience, and increasingly is an expected part of graduate school training. While such programs are commonly available to undergraduates, there is a growing need for career support to be offered to graduate students. Making the case for resources can be a challenge in this domain, however. Research on the impact of career services for graduate students and post-doctoral scholars is a growing scholarly concern. However, there remains a need to better understand what level of intervention is most appropriate: What kind of activities, how much time, and what resources would best serve the professional development needs of graduate students and post-doctoral scholars? And to answer these questions, a more foundational one: what activities are drawing the attention of graduate students and post doctoral trainees, and in what activities are they spending their time? In this manuscript, we describe how Our University approached this research question by developing an online data tracking system to capture graduate and post-doctoral trainee participation in one co-curricular professional development program. We demonstrate how this data tracking system can be used to advocate for institutional resources in career development programming, for research, and for practical purposes such as advocating for institutional support and for program design and assessment.
Thermodynamics of smooth models of pseudo–Anosov homeomorphisms
Authors: VECONI DOMINIC 
Published: May 2021

AbstractWe develop a thermodynamic formalism for a smooth realization of pseudo-Anosov surface homeomorphisms. In this realization, the singularities of the pseudo-Anosov map are assumed to be fixed, and the trajectories are slowed down so the differential is the identity at these points. Using Young towers, we prove existence and uniqueness of equilibrium states for geometric t-potentials. This family of equilibrium states includes a unique SRB measure and a measure of maximal entropy, the latter of which has exponential decay of correlations and the central limit theorem.
Hegel's Concept of the Familiar: Toward a Philosophical Study
Authors: Aldouri Hammam 
Published: May 2021

AbstractOne of the most memorable lines of Hegel's oeuvre is from the preface to his Phenomenology of Spirit: ‘Quite generally, the familiar, just because it is familiar, is not cognitively understood.’ Surprisingly, relatively little philosophical attention has been paid to the notion of ‘the familiar’ in Hegel scholarship. This essay aims to rectify this lack by offering a preliminary inquiry in what the notion means across Hegel's work. It does so by focusing on three underexplored moments in Hegel's work: (1) the exposition of the logic of appearance in the description and diagnosis of seventeenth and eighteenth century Dutch painting in the lecture notes from the 1823 Berlin lectures on the philosophy of fine art; (2) the function of institutionalized practice in Hegel's Tübingen essay of 1793; and (3) the conjunctural relation of the familiar with philosophical terminology in an entry from the ‘Aphorisms from the Wastebook.’ Through a careful reading of these three moments, I will show that the familiar is a point that constellates multiple processes, mechanisms and apparatuses that, when grasped in their complex totality, functions as the ‘prius’ (priority/prioritization/first moment) of Hegel's speculative philosophy.