bluuebunny/crossref_metadata_2025_split huggingface dataset:
An isogenic human iPSC model unravels neurodevelopmental abnormalities in SMA
Authors: Grass Tobias , Rosignol Ines , Thomas Joshua , Buchner Felix , Dokuzluoglu Zeynep , Dalinskaya Anna , Becker Jutta , Wirth Brunhilde , Rodriguez-Muela Natalia 
Published: January 2023

AbstractWhether neurodevelopmental defects underlie the selective neuronal death that characterizes neurodegenerative diseases is becoming an intriguing question. To address it, we focused on the motor neuron (MN) disease Spinal Muscular Atrophy (SMA), caused by reduced levels of the ubiquitous protein SMN. Taking advantage of the first isogenic human induced pluripotent stem cell-derived SMA model that we have generated and a spinal cord organoid system, here we report that the relative and temporal expression of early neural progenitor and MN markers is altered in SMA. Furthermore, the corrected isogenic controls only partially reverse these abnormalities. These findings raise the relevant clinical implication that SMN-increasing treatments might not fully amend SMA pathological phenotypes. The approach we have taken demonstrates that the discovery of new disease mechanisms is greatly improved by using human isogenic models. Moreover, our study implies that SMA has a developmental component that might trigger the MN degeneration.
Transfer Learning with False Negative Control Improves Polygenic Risk Prediction
Authors: Jeng X. Jessie , Hu Yifei , Tzeng Jung-Ying 
Published: January 2023

AbstractPolygenic risk score (PRS) is a quantity that aggregates the effects of variants across the genome and estimates an individual’s genetic predisposition for a given trait. PRS analysis typically contains two input data sets: base data for effect size estimation and target data for individual-level prediction. Given the availability of large-scale base data, it becomes more common that the ancestral background of base and target data do not perfectly match. In this paper, we treat the GWAS summary information obtained in the base data as knowledge learned from a pre-trained model, and adopt a transfer learning framework to effectively leverage the knowledge learned from the base data that may or may not have similar ancestral background as the target samples to build prediction models for target individuals. Our proposed transfer learning framework consists of two main steps: (1) conducting false negative control (FNC) marginal screening to extract useful knowledge from the base data; and (2) performing joint model training to integrate the knowledge extracted from base data with the target training data for accurate trans-data prediction. This new approach can significantly enhance the computational and statistical efficiency of joint-model training, alleviate over-fitting, and facilitate more accurate trans-data prediction when heterogeneity level between target and base data sets is small or high.Author summaryPolygenic risk score (PRS) can quantify the genetic predisposition for a trait. PRS construction typically contains two input datasets: base data for variant-effect estimation and target data for individual-level prediction. Given the availability of large-scale base data, it becomes common that the ancestral background of base and target data do not perfectly match. In this paper, we introduce a PRS method under a transfer learning framework to effectively leverage the knowledge learned from the base data that may or may not have similar background as the target samples to build prediction models for target individuals. Our method first utilizes a unique false-negative control strategy to extract useful information from base data while ensuring to retain a high proportion of true signals; it then applies the extracted information to re-train PRS models in a statistically and computationally efficient fashion. We use numerical studies based on simulated and real data to show that the proposed method can increase the accuracy and robustness of polygenic prediction across different ranges of heterogeneities between base and target data and sample sizes, reduce computational cost in model re-training, and result in more parsimonious models that can facilitate PRS interpretation and/or exploration of complex, non-additive PRS models.
The Respiratory Syncytial Virus M2-2 protein is targeted for proteasome degradation and inhibits translation and stress granules assembly
Authors: Scudero Orlando Bonito , Santiago Verônica Feijoli , Palmisano Giuseppe , Simabuco Fernando Moreira , Ventura Armando Morais 
Published: January 2023

AbstractThe M2-2 protein from the respiratory syncytial virus (RSV) is a 10 kDa protein expressed by the second ORF of the viral gene M2. During infection, M2-2 has been described as the polymerase cofactor responsible for promoting genome replication. This function was first inferred by infection with a mutant virus lacking the M2-2 ORF, in which viral genome presented delayed accumulation in comparison to wild-type virus. In accordance with this phenotype, it has been recently shown that M2-2 promotes changes in interactions between the polymerase and other viral proteins at early stages of infection. Despite its well-explored role in the regulation of the polymerase activity, little has been made to investigate the relationship of M2-2 with cellular proteins. In fact, a previous report showed poor recruitment of M2-2 to viral structures, with the protein being mainly localized to the nucleus and cytoplasmic granules. To unravel which other functions M2-2 exerts during infection, we expressed the protein in HEK293T cells and performed proteomic analysis of co-immunoprecipitated partners, identifying enrichment of proteins involved with regulation of translation, protein folding and mRNA splicing. In approaches based on these data, we found that M2-2 expression downregulates eiF2α phosphorylation and inhibits stress granules assembly under arsenite induction. In addition, we also verified that M2-2 inhibits translation initiation, and is targeted for proteasome degradation, being localized to granules composed by defective ribosomal products at the cytoplasm. These results suggest that besides its functions in the regulation of genome replication, M2-2 may exert additional functions to contribute to successful RSV infection.Author summaryExploring how viruses take control of the cellular machinery is a common strategy to understand the infection process and to identify targets for inhibition of virus replication. In this work we investigated the cellular functions of the protein M2-2 from the respiratory syncytial virus. Although this virus is an important pathogen responsible for respiratory infections in immunocompromised individuals, currently there are no vaccines or effective treatments to inhibit its infection. Our findings showed that the protein M2-2 interferes with protein synthesis, being able to downregulate the assembly of stress granules during stress stimuli. Besides, we verified the relationship between M2-2 and the proteasome machinery, which is responsible for protein degradation and is also involved with protein synthesis. These results present new functions for the protein M2-2, indicating additional mechanisms utilized by the virus to facilitate infection, providing new perspectives for the search of antiviral targets.
Mapping the dynamic cell surface interactome of high-density lipoprotein reveals Aminopeptidase N as modulator of its endothelial uptake
Authors: Frey Kathrin , Rohrer Lucia , Potapenko Anton , Goetze Sandra , von Eckardstein Arnold , Wollscheid Bernd 
Published: January 2023

AbstractHeterogeneous high-density lipoprotein (HDL) particles, which can contain hundreds of proteins, affect human health and disease through dynamic molecular interactions with cell surface proteins. How HDL mediates its long-range signaling functions and interactions with various cell types is largely unknown. Due to the complexity of HDL, we hypothesize that multiple receptors engage with HDL particles resulting in condition-dependent receptor-HDL interaction clusters at the cell surface. Here we used the mass spectrometry-based and light-controlled proximity labeling strategy LUX-MS in a discovery-driven manner to decode HDL-receptor interactions. Surfaceome nanoscale organization analysis of hepatocytes and endothelial cells using LUX-MS revealed that the previously known HDL-binding protein scavenger receptor SCRB1 is embedded in a cell surface protein community, which we term HDL synapse. Modulating the endothelial HDL synapse, composed of 60 proteins, by silencing individual members showed that the HDL synapse can be assembled in the absence of SCRB1 and that the members are interlinked. The aminopeptidase AMPN (also known as CD13) was identified as an HDL synapse member that directly influences HDL uptake into the primary human aortic endothelial cells (HAECs). Our data indicate that preformed cell surface residing protein complexes modulate HDL function and suggest new theragnostic opportunities.
Computational workflow and interactive analysis of single-cell expression profiling of islets generated by the Human Pancreas Analysis Program
Authors: Patil Abhijeet R. , Schug Jonathan ,   the HPAP Consortium, Naji Ali , Kaestner Klaus H. , Faryabi Robert B. , Vahedi Golnaz 
Published: January 2023

AbstractType 1 and Type 2 diabetes are distinct genetic diseases of the pancreas which are defined by the abnormal level of blood glucose. Understanding the initial molecular perturbations that occur during the pathogenesis of diabetes is of critical importance in understanding these disorders. The inability to biopsy the human pancreas of living donors hampers insights into early detection, as the majority of diabetes studies have been performed on peripheral leukocytes from the blood, which is not the site of pathogenesis. Therefore, efforts have been made by various teams including the Human Pancreas Analysis Program (HPAP) to collect pancreatic tissues from deceased organ donors with different clinical phenotypes. HPAP is designed to define the molecular pathogenesis of islet dysfunction by generating detailed datasets of functional, cellular, and molecular information in pancreatic tissues of clinically well-defined organ donors with Type 1 and Type 2 diabetes. Moreover, data generated by HPAP continously become available through a centralized database, PANC-DB, thus enabling the diabetes research community to access these multi-dimensional data prepublication. Here, we present the computational workflow for single-cell RNA-seq data analysis of 258,379 high-quality cells from the pancreatic islets of 67 human donors generated by HPAP, the largest existing scRNA-seq dataset of human pancreatic tissues. We report various computational steps including preprocessing, doublet removal, clustering and cell type annotation across single-cell RNA-seq data from islets of four distintct classes of organ donors, i.e. non-diabetic control, autoantibody positive but normoglycemic, Type 1 diabetic, and Type 2 diabetic individuals. Moreover, we present an interactive tool, called CellxGene developed by the Chan Zuckerberg initiative, to navigate these high-dimensional datasets. Our data and interactive tools provide a reliable reference for singlecell pancreatic islet biology studies, especially diabetes-related conditions.
Reward me or charity: The impact of mobile e-commerce platforms' loyalty programme reward types on participation intention
Authors: Zhou Yanju , Lu Cuilian , Yu Yi 
Published: January 2023

PurposeWith the development of e-commerce, loyalty programmes (LPs) are gradually being adopted in the online retailing environment to improve consumer loyalty. This article determines the factors that affect consumers' LP participation intention on mobile e-commerce platforms to help these platforms improve their performance.Design/methodology/approachThis article focusses on LP reward types and divides them into self-oriented rewards or altruistic rewards. Two experiments are conducted to test the proposed hypotheses. After online data collection, data analysis is performed.FindingsLP participation intention with altruistic rewards is significantly stronger than that with self-oriented rewards. Perceived value plays a complete mediating role in the impact of reward type on participation intention, while a point leaderboard plays a positive moderating role in the impact of reward type on perceived value.Practical implicationsThis study’s findings can improve the design of LPs by mobile e-commerce platforms.Originality/valueThis article focusses on LPs in the online environment, a stream of research that is limited. The results also have implications for prosocial relationship marketing programmes.
Individuals' attitudes about organizational change: relationship between BPM and resistance to change
Authors: Fernandes dos Santos Nataly Inêz , Aires Renan Felinto de Farias 
Published: January 2023

PurposeThe aim of this article is to investigate individuals' attitudes about organizational change, considering implementation of business process management (BPM) and resistance to change.Design/methodology/approachThe study examines the attitudes of subjects that experienced organizational change in the context of BPM in Brazil. In order to measure resistance to organizational change, 22 interviews were conducted using a script adapted from Pereira et al. (2019). The study considered two main agents: BPM implementers and end-users. Data were analyzed qualitatively via content analysis.FindingsThe results provided interesting insights. In relation to the individuals' attitudes, satisfaction, fear, stress and anxiety were the most frequently reported. However, opinions contradict the negative feelings expressed, given that organizational benefits, facility and pleasure at work and personal benefits were the most frequently reported. In regard to behavior, individuals approved change and in general accepted it. Finally, in terms of confidence in management, the subjects reported leadership and trusting their bosses as positive points.Research limitations/implicationsStudy limitations include the difficulty in finding end-users on LinkedIn, the fact that convenience sampling was used and the possible false memory of respondents.Originality/valueThe approach used in this study provided a relevant contribution to the area under study, primarily via the new findings, that is, elements of resistance to change that emerged from the data.
Education for sustainable development in higher education institutions: an approach for effective interdisciplinarity
Authors: Mokski Elliott , Leal Filho Walter , Sehnem Simone , Andrade Guerra José Baltazar Salgueirinho Osório de 
Published: January 2023

Purpose
This paper aims to develop an improved and harmonized approach to interdisciplinarity in education for sustainable development (ESD)within higher education institutions (HEIs), focusing on maximizing the mobilization of students from all academic disciplines. An attempt is made to reconcile varying strategies for the implementation of interdisciplinary ESD content in HEIs, studying the relative merit and benefit of those strategies and crafting a new approach to combining them, where possible.

Design/methodology/approach
This work relies on a robust review and analysis of existing literature proposals on the implementation of ESD in HEIs to elaborate an integrated approach to interdisciplinarity. Specifically, a scoping literature review is applied, analyzing the existing approaches to ESD in HEIs as well as the challenges observed in their implementation. Using this theoretical framework, this paper evaluates the compatibility and efficiency of the approaches currently implemented. Based on this analysis, an integrative approach is outlined, building upon and combining existing proposals.

Findings
Building on existing literature, this study identifies two main trends for interdisciplinarity in ESD in HEIs: integration into existing disciplinary curricula and new, stand-alone ESD curricula. This paper suggests adopting the two approaches simultaneously, to reach students from all academic disciplines, especially those with minimal exposure to ESD through their own discipline. Furthermore, this paper stresses that these dual curricula strategies should be combined with further interdisciplinary research initiatives as well as extensive leveraging of technology and e-learning.

Originality/value
This study bridges the gap between diverging visions for ESD in HEIs, harmonizing strategies from the literature to outline a new, multilateral strategy. Furthermore, it extensively studies the need for increased engagement into ESD of students from underrepresented disciplines, including the humanities. This engagement has been little addressed in the literature, rendering the proposed approach original insofar as it outlines the ways to improve current approaches to ESD in HEIs.
Understanding the role of perceived enjoyment, self-efficacy and system accessibility: digital natives' online learning intentions
Authors: Bagdi Himanshu , Bulsara Hemantkumar P. 
Published: January 2023

PurposeThis research aims to look at how students feel about taking online learning (OL) while studying in higher education institutions (HEIs) using an extended technology acceptance model (TAM). The study looked into the factors that influence students' decisions to use OL, which helps meet their individual needs beyond the confines of the traditional classroom.Design/methodology/approachA study of 284 students from the universities of Gujarat in India was conducted using a self-administered questionnaire. The partial least square-structural equation modelling (PLS-SEM) was used to analyse the study's test results.FindingsThe result of the study confirms that perceived enjoyment (PE) has a fully significant relationship with the behavioural intention to use online learning (IOL), whereas self-efficacy (SE) is partially supported and system accessibility (ACC) has an insignificant impact on the IOL.Research limitations/implicationsThough the study focussed on the TAM to analyse the proposed model, future studies should address other constructs like ICT infrastructure, perceived behavioural control, experience, etc.Originality/valueThis research identified the key variables of students' intention to adapt to OL and offered a path to encourage higher education students to use online education as a classroom alternative. Educators in Indian administrative positions can better facilitate OL adoption amongst their student bodies by developing a keener awareness of students' goals and the factors influencing their views on the topic.
Hitchhiking in board interlocks? The externality of partner innovation
Authors: Jiang Yusi , Zhao Yapu , Dang Beilei 
Published: January 2023

PurposeThis study explores the influence of partner innovation in board interlock networks on a firm's innovation tendency.Design/methodology/approachThis study collects a sample of publicly listed Chinese firms from 2008 to 2017 and uses fixed-effects ordinary least squares regressions to analyze the data.FindingsThis study shows that interlocking partners with different innovation levels than that of the focal firm affect its innovation tendency in distinct ways. For more innovative partners, the innovation level has a U-shaped effect on the focal firm's innovation tendency. In the case of less innovative partners, the innovation level facilitates the focal firm's innovation tendency.Originality/valueGoing beyond previous research that emphasized the role of interorganizational networks in facilitating firm innovation through a unitary learning effect, this study differentiates network partners into two categories based on their relative level of innovation compared with the focal firm and takes the hitchhiking effect into account to highlight potential obstacles in the learning process depending on the innovation conditions of partners. The study advances the literature on organizational learning, social networks and innovation.
A new empirical approach for mitigating exploding implicit prices in mixed multinomial logit models
Authors: Crastes dit Sourd Romain 
Published: January 2023

AbstractThis paper introduces a new shifted negative log‐normal distribution for the price parameter in mixed multinomial logit models. The new distribution, labeled as the μ‐shifted negative log‐normal distribution, has desirable properties for welfare analysis and in particular a point mass that is further away from zero than the negative log‐normal distribution. This contributes to mitigating the “exploding” implicit prices issue commonly found when the price parameter is specified as negative log‐normal and the model is in preference space. The new distribution is tested on five stated preference datasets. Comparisons are made with standard alternative approaches such as the willingness‐to‐pay (WTP) space approach. It is found that the μ‐shifted distribution yields substantially lower mean marginal WTP estimates compared to the negative log‐normal specification and similar to the values derived from models estimated in WTP‐space with flexible distributions, while at the same time fitting the data as well as the negative log‐normal specification.
Soluble E‐cadherin: A marker of genital epithelial disruption
Authors: Liu Rachel , Armstrong Eric , Constable Shirley , Buchanan Lane B , Mohammadi Avid , Galiwango Ronald M , Huibner Sanja , Perry Marie C , Prodger Jessica L , Coburn Bryan , Kaul Rupert 
Published: January 2023

AbstractProblemThe genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity requires biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. The purpose of this study was to evaluate soluble E‐cadherin (sE‐cad) as a marker of genital epithelial disruption.Method of studyUsing in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE‐cad, IL‐6, IL‐1β, and IL‐1α levels following mechanical disruption. We also assessed changes in sE‐cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE‐cad in coronal sulcus swabs to membrane‐bound E‐cadherin in the overlying foreskin tissue in Ugandan men.ResultssE‐cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL‐1β and IL‐1α; this was followed by a delayed increase in IL‐6 levels. In vivo results confirmed that sE‐cad levels in cervicovaginal secretions were elevated 6 h after cytobrush sampling when compared to baseline. Furthermore, levels of sE‐cad in the prepuce were inversely correlated with the amount of membrane‐bound E‐cadherin of overlying tissue.ConclusionOur results validate the use of sE‐cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.