bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel Modelling of Gaze from Hearing-impaired Listeners following a Realistic Conversation
Authors: Shiell Martha M. , Høy-Christensen Jeppe , Skoglund Martin A. , Keidser Gitte , Zaar Johannes , Rotger-Griful Sergi 
Published: November 2022

AbstractPurposeThere is a need for outcome measures that predict real-world communication abilities in hearing-impaired people. We outline a potential method for this and use it to answer the question of when, and how much, hearing-impaired listeners look towards a new talker in a conversation.MethodTwenty-two older hearing-impaired adults followed a pre-recorded two-person audiovisual conversation in the presence of babble noise. We compared their eye-gaze direction to the conversation in two multilevel logistic regression (MLR) analyses. First, we split the conversation into events classified by the number of active talkers within a turn or a transition, and we tested if these predicted the listener’s gaze. Second, we mapped the odds that a listener gazed towards a new talker over time during a conversation transition.ResultsWe found no evidence that our conversation events predicted changes in the listener’s gaze, but the listener’s gaze towards the new talker during a silent-transition was predicted by time: The odds of looking at the new talker increased in an s-shaped curve from at least 0.4 seconds before to 1 second after the onset of the new talker’s speech. A comparison of models with different random effects indicated that more variance was explained by differences between individual conversation events than by differences between individual listeners.ConclusionMLR modelling of eye-gaze during talker transitions is a promising approach to study a listener’s perception of realistic conversation. Our experience provides insight to guide future research with this method.
PathExpSurv: Pathway Expansion for Explainable Survival Analysis and Disease Gene Discovery
Authors: Hou Zhichao , Leng Jiacheng , Yu Jiating , Xia Zheng , Wu Ling-Yun 
Published: November 2022

AbstractMotivationIn the field of biology and medicine, the interpretability and accuracy are both important when designing predictive models. The interpretability of many machine learning models such as neural networks is still a challenge. Recently, many researchers utilized prior information such as biological pathways to develop bioinformatics methods based on neural networks, so that the prior information can provide some insights and interpretability for the models. However, the prior biological knowledge may be incomplete and there still exists some unknown information to be explored.ResultsWe proposed a novel method, named PathExpSurv, to gain an insight into the black-box model of neural network for cancer survival analysis. We demonstrated that PathExpSurv could not only incorporate the known prior information into the model, but also explore the unknown possible expansion to the existing pathways. We performed downstream analyses based on the expanded pathways and successfully identified some key genes associated with the diseases and original pathways.AvailabilityPython source code of PathExpSurv is freely available athttps://github.com/Wu-Lab/PathExpSurv.Contact:lywu@amss.ac.cnSupplementary informationSupplementary data are available atBioinformaticsonline.
Dynamic changes in the transcriptome of oocytes during adolescent-onset PCOS in mice
Authors: Danfeng Du , Ke Deng , Dengxuan Fan , Congjian Xu 
Published: November 2022

Abstract(1) Background: This study aimed to explore temporal changes in the transcriptome of oocytes in an adolescent-onset polycystic ovarian syndrome (PCOS) mouse model. (2) Methods: An adolescent-onset PCOS mouse model was established using DHEA. Genes with a similar expression trend over time were identified using trend analysis. KEGG pathway enrichment analysis and gene regulatory network diagrams were examined for signaling pathways to identify potential hub genes related to the pathogenesis of PCOS. (3) Results: Four main trends of gene expression were extracted, of which six combinations of Venn diagrams were generated. Differentially expressed genes were mainly enriched in oxidative phosphorylation, cell cycle, P53 signaling pathway. Cell cycle-related genes (Skp1, Ccnb1, Orc1 and 5, Wee2, Mapk3, Cdc20) were abnormally down-regulated in the DHEA group. Ptges3 was the top1 DEGs at the initial stage of PCOS modeling. (4) Conclusion: This study provides a novel insight into the altered transcriptome of oocytes from PCOS mice. mtDNA-related genes and Cell cycle-related genes play the most important role in the development of PCOS. Ptges3 was the one of the top DEGs which was up-regulated in DHEA group at the initial stage of modeling, which suggested it may play an important role in the early stage of PCOS.
Volumetric microscopy of CD9 and CD63 reveals distinct subpopulations and novel structures of extracellular vesiclesin situin triple negative breast cancer cells
Authors: White Elizabeth D. , Walker Nykia D. , Yi Hannah , Dinner Aaron R. , Scherer Norbert F. , Rosner Marsha Rich 
Published: November 2022

AbstractSecreted extracellular vesicles (EVs) are now known to play multifaceted roles in biological processes such as immune responses and cancer. The two primary classes of EVs are defined in terms of their origins: exosomes are derived from the endosomal pathway while microvesicles (ectosomes) bud from the cell membrane. However, it remains unclear whether the contents, sizes, and localizations of subpopulations of EVs can be used to associate them with the two primary classes. Here, we use confocal microscopy and high-resolution volumetric imaging to study intracellular localization of the EV markers CD9 and CD63 prior to EV export from cells. We find significantly different spatial expression of CD9 and CD63. CD9 is primarily localized in microvesicles, while CD63 is detected exclusively in exosomes. We also observe structures in which CD63 forms a shell that encapsulates CD9 and interpret them to be multi-vesicular bodies. The morphology and location within the endoplasmic reticulum of these shell-like structures are consistent with a role in differential sorting and export of exosomes and microvesicles. Ourin situimaging allows unambiguous identification and tracking of EVs from their points of origin to cell export, and suggest that CD9 and CD63 can be used as biomarkers to differentiate subpopulations of EVs.
Analysis of alternative polyadenylation from long-read or short-read RNA-seq with LAPA
Authors: Çelik Muhammed Hasan , Mortazavi Ali 
Published: November 2022

AbstractMotivationAlternative polyadenylation (APA) is a major mechanism that increases transcriptional diversity and regulates mRNA abundance. Existing computational tools to analyze APA have low precision because these tools are designed for short-read RNA-seq, which is a suboptimal data source to study APA. Long-read RNA-seq (LR-RNA-seq) accurately detects complete transcript isoforms with poly(A)-tails, providing an ideal data source to study APA. However, current computational tools are incompatible with LR-RNA-seq.ResultsHere, we introduce LAPA, a computational toolkit to study alternative polyadenylation (APA) from diverse data sources such as LR-RNA-seq and short-read 3’ sequencing (3’-seq). LAPA counts and clusters reads with poly(A)-tail, then performs peak-calling to detect poly(A)-site in a data source agnostic manner. The resulting peaks are annotated based on genomics features and regulatory sequence elements such as presence of a poly(A)-signal. Finally, LAPA can perform robust statistical testing and multiple testing correction to detect differential APA.We analyzed ENCODE LR-RNA-seq data from human WTC11, mouse C2C12 myoblast, and C2C12-derived differentiated myotube cells using LAPA. Comparing LR-RNA-seq from different platforms and library preparation methods against 3’-seq shows that LR-RNA-seq detects poly(A)-sites with a performance of 75% precision at 57% recall. Moreover, LAPA consistently improved TES validation by at least 25% over the baseline transcriptome annotation generated by TALON, independent of protocol or platform. Differential APA analysis detected 788 statistically significant genes with unique polyadenylation signatures between undifferentiated myoblast and differentiated myotube cells. Among these genes, 3’ UTR elongation is significantly associated with higher expression, while shortening is linked with lower expression. This analysis reveals a link between cell state/identity and APA. Overall, our results show that LR-RNA-seq is a reliable data source for the study of post-transcriptional regulation by providing precise information about alternative polyadenylation.AvailabilityLAPA is publicly available athttps://github.com/mortazavilab/lapaand PyPI.Contact::ali.mortazavi@uci.edu
ToDD: Topological Compound Fingerprinting in Computer-Aided Drug Discovery
Authors: Demir Andac , Coskunuzer Baris , Segovia-Dominguez Ignacio , Chen Yuzhou , Gel Yulia , Kiziltan Bulent 
Published: November 2022

AbstractIn computer-aided drug discovery (CADD), virtual screening (VS) is used for identifying the drug candidates that are most likely to bind to a molecular target in a large library of compounds. Most VS methods to date have focused on using canonical compound representations (e.g., SMILES strings, Morgan fingerprints) or generating alternative fingerprints of the compounds by training progressively more complex variational autoencoders (VAEs) and graph neural networks (GNNs). Although VAEs and GNNs led to significant improvements in VS performance, these methods suffer from reduced performance when scaling to large virtual compound datasets. The performance of these methods has shown only incremental improvements in the past few years. To address this problem, we developed a novel method using multiparameter persistence (MP) homology that produces topological fingerprints of the compounds as multidimensional vectors. Our primary contribution is framing the VS process as a new topology-based graph ranking problem by partitioning a compound into chemical substructures informed by the periodic properties of its atoms and extracting their persistent homology features at multiple resolution levels. We show that the margin loss fine-tuning of pretrained Triplet networks attains highly competitive results in differentiating between compounds in the embedding space and ranking their likelihood of becoming effective drug candidates. We further establish theoretical guarantees for the stability properties of our proposed MP signatures, and demonstrate that our models, enhanced by the MP signatures, outperform state-of-the-art methods on benchmark datasets by a wide and highly statistically significant margin (e.g., 93% gain for Cleves-Jain and 54% gain for DUD-E Diverse dataset).
Density-dependent selection during range expansion affects expansion load in life-history traits
Authors: Urquhart-Cronish Mackenzie , Angert Amy L. , Otto Sarah P. , MacPherson Ailene 
Published: November 2022

AbstractModels of range expansion have independently explored fitness consequences of life-history trait evolution and increased rates of genetic drift—or “allele surfing”—during spatial spread, but no previous model has examined the interactions between these two processes. Here, we explore an ecologically complex range expansion scenario that combines density-dependent selection with allele surfing, using spatially explicit simulations to asses the genetic and fitness consequences of density-dependent selection on the evolution of life-history traits. We demonstrate that density-dependent selection on the range edge acts differently depending on the life-history trait and can either diminish or enhance allele surfing. Specifically, we show that selection on the range edge is always weaker at sites affecting competitive ability (K-selected traits) than intrinsic growth rate ((r-selected traits). We then link differences in the frequency of deleterious mutations to differences in the efficacy of selection and rate of mutation accumulation across distinct life-history traits. Finally, we demonstrate the fitness consequences of accumulated deleterious mutations for different life-history traits are related to the population density in which they are expressed. Our work highlights the complex relationship between ecology and expressed genetic load, which will be important to consider when interpreting both experimental and field studies of range expansion.
Translational fusion of terpene synthases enhances metabolic flux by increasing protein stability
Authors: Cheah Li Chen , Liu Lian , Stark Terra , Plan Manuel R. , Peng Bingyin , Lu Zeyu , Schenk Gerhard , Sainsbury Frank , Vickers Claudia E. 
Published: November 2022

ABSTRACTThe end-to-end fusion of enzymes that catalyse successive steps in a reaction pathway is a metabolic engineering strategy that has been successfully applied in a variety of pathways and is particularly common in terpene bioproduction. Despite its popularity, limited work has been done to interrogate the mechanism of metabolic enhancement from enzyme fusion. We observed a remarkable >110-fold improvement in nerolidol production upon translational fusion of nerolidol synthase (a sesquiterpene synthase) to farnesyl diphosphate synthase. This delivered a titre increase from 29.6 mg/L up to 4.2 g/L nerolidol in a single engineering step. Whole-cell proteomic analysis revealed that nerolidol synthase levels in the fusion strains were greatly elevated compared to the non-fusion control. Similarly, the fusion of nerolidol synthase to non-catalytic domains also produced comparable increases in titre, which coincided with improved enzyme expression. When farnesyl diphosphate synthase was fused to other terpene synthases, we observed more modest improvements in terpene titre (1.9- and 3.8-fold), which corresponds to increases of a similar magnitude in terpene synthase expression. Therefore, increasedin vivoenzyme levels – resulting from improved expression and/or stability – is likely to be a major driver of catalytic enhancement from enzyme fusion.
Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells
Authors: Kobayashi-Ishihara Mie , Smutná Katarína Frazão , Alonso Florencia E. , Argilaguet Jordi , Esteve-Codina Anna , Geiger Kerstin , Genescà Meritxell , Grau-Expósito Judith , Duran-Castells Clara , Rogenmoser Selina , Böttcher René , Jungfleisch Jennifer , Oliva Baldomero , Martinez Javier P. , Li Manqing , David Michael , Yamagishi Makoto , Ruiz-Riol Marta , Brander Christian , Tsunetsugu-Yokota Yasuko , Buzon Maria J. , Díez Juana , Meyerhans Andreas 
Published: November 2022

AbstractLatency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1- infected individuals,SLFN12expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.
Calculating a life: classification, valuation and compensation in the British abolition of slavery
Authors: Jeacle Ingrid 
Published: November 2022

PurposeThis paper examines the calculative practices used by the Slave Compensation Commission to value a slave for the purposes of compensating slave owners on the abolishment of slavery across the British colonies in 1833. It contributes to accounting research in the field of valuation, particularly to understanding the practices of valuing human life.Design/methodology/approachThe methodology is primarily archival and draws on the records of the Slave Compensation Commission held at the British National Archives (Kew).FindingsThe paper makes two contributions to the literature. Firstly, it contributes to the valuation studies literature by suggesting the significance of understanding the practice of valuation as a product of the dynamics of strategic action fields (Fligstein and McAdam, 2012). Secondly, it contributes to the theory of strategic action fields by revealing the role of calculative technologies in supporting the organizational apparatus of valuation within the Slave Compensation Commission, and therefore suggests the powerful role of accounting in stabilizing a strategic action field.Originality/valueThe paper provides novel insights into the monetary commensuration of life and the role of calculative technologies in that valuation process.
Crowdfunding and innovation: a bibliometric review and future research agenda
Authors: Bargoni Augusto , Ferraris Alberto , Bresciani Stefano , Camilleri Mark Anthony 
Published: November 2022

PurposeThis article aims to investigate the status of and the trends in the intertwining of crowdfunding and innovation literature by identifying, evaluating and synthesizing the findings from previous research. This paper provides a bibliometric meta-analysis of the already substantial and growing literature on innovation and crowdfunding research.Design/methodology/approachUsing a bibliometric approach, this research scrutinizes all articles that include terms related to “crowdfunding” and “innovation” (in their title, abstract or keywords) in Elsevier’s Scopus database. VosViewer and Bibliometrix package in R have been used to analyse 150 articles.FindingsThe results suggest that there are three main research clusters in the innovation and crowdfunding literature. The first cluster highlights the role of crowdfunding in fostering radical and incremental innovation. The second cluster focuses on the concept of openness and its effect on innovation in crowdfunding campaigns, while the third cluster explains the role of platforms’ innovation in crowdfunding success.Originality/valueTaking a holistic perspective, this contribution advances new knowledge on the intertwining of crowdfunding and innovation research fields. It implies that crowdfunding is facilitating the flow of knowledge between different stakeholders, including project initiators and crowd investors, among others, as they all benefit from open innovation platforms.
Indoor environmental quality (IEQ) in the home workplace in relation to mental well-being
Authors: Boegheim Bouke , Appel-Meulenbroek Rianne , Yang Dujuan , Loomans Marcel 
Published: November 2022

Purpose
This paper aims to study employee mental health in relation to workplace design and indoor environmental quality (IEQ) when working from home, which has received little attention. The trend toward hybrid working urges for more knowledge.

Design/methodology/approach
Through a mixed data collection method, this study analyzed potential relationships (between mental health, workplace design and IEQ) from information obtained through a cross-sectional survey, repeated point-in-time surveys and desk-based IEQ sensors at home. Data were collected in April 2020 during a national COVID-19 lockdown in The Netherlands amongst 36 subjects. They all worked full time from home in this period and together completed 321 point-in-time surveys. The three data sets were combined and analyzed using bivariate and path analysis.

Findings
Outcomes indicate that subjective and objective IEQ conditions, workplace suitability and distraction affect employee mental health in the home workplace in a similar way as in the office. Being satisfied with the noise level increases concentration, self-reported well-being and engagement. High sound pressure levels (>58 dB) increased tension or nervous feelings.

Originality/value
To the best of the authors’ knowledge, this study is one of the first to explore employee mental health in relation to simultaneously assessed (perceived and measured) multiple IEQ parameters in the home workplace.
Crop diversity and farm income: evidence from a large-scale national survey
Authors: Sehgal Vandana 
Published: November 2022

Purpose
This study aims to evaluate the effectiveness of crop diversification in increasing the income of farm households. In addition, this study introduces the impact of natural disasters in the analysis to determine how diversification helps mitigate the negative effect of disasters on farm income. More importantly, the study also analyses the effect of diversification on farm income by farm class to see where the benefits of diversification are concentrated.

Design/methodology/approach
This study uses a linear model, in which agricultural income is expressed as a function of diversification, natural disasters and several control variables. Diversification is measured using the Simpson index of diversification. The linear model is enhanced with the inclusion of an interaction term of natural disasters with the diversification index to shed light on the role of diversification in negating their harmful effect on agricultural income. Finally, to analyze the impact of institutional variables on farm income, the interactions of diversification with irrigation, insurance, usage of technical information and formal training are incorporated in the linear model.

Findings
The study highlights the importance of demographic, farm and institutional variables in raising farm income. The study suggests that an increase in education level, irrigation, usage of technical information and possession of Kisan Credit Card (KCC) have a positive impact on agricultural income. The study reveals that crop diversification has a positive impact on farm income and the benefits of diversification are conditioned by institutional factors. Thus, there is a need for policy intervention to ensure increased irrigation facilities along with extension services to provide information to the farm households. It has been found that small farmers gain more from crop diversification than larger farmers. Furthermore, the results show that natural disasters negatively impact farm income, but their impact can be mitigated by higher levels of diversification.

Originality/value
The results of the study are based on the recent unit-level data from the 77th Round of the National Sample Survey Office survey. The survey covers a large number of farm households and reports information for the year 2018–2019.