bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-cancer transcriptomic analysis reveals a tissue-specific loss of identity
Authors: dos Santos Gabriel Arantes , Chatsirisupachai Kasit , Avelar Roberto A. , de Magalhães João Pedro 
Published: December 2022

AbstractUnderstanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx. We found a loss of cell identity during ageing in around 40% of tissues. In cancer, we observed a pattern of downregulation of genes specific to the tissue of origin of the tumor for most cancer types. Moreover, we observed an activation of genes not usually expressed in a tissue as well as an upregulation of genes specific to other tissues in cancer. These patterns in cancer were associated with patient survival. The age of the patient, however, does not influence these patterns. Thus, we identified a moderate but statistically significant pattern of loss of cell identity in ageing, and a clear pattern in cancer, where during tumorigenesis, cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.
Reanalysis of mtDNA mutations of human primordial germ cells (PGCs) reveals NUMT contamination and suggests that selection in PGCs may be positive
Authors: Fleischmann Zoë , Cote-L’Heureux Auden , Franco Melissa , Oreshkov Sergey , Annis Sofia , Khrapko Mark , Aidlen Dylan , Popadin Konstantin , Woods Dori C. , Tilly Jonathan L. , Khrapko Konstantin 
Published: December 2022

AbstractThe resilience of the mitochondrial genome (mtDNA) to a high mutational pressure depends, in part, on negative purifying selection in the germline. A paradigm in the field has been that such selection, at least in part, takes place in primordial germ cells (PGCs). Specifically, Floros et al. (Nature Cell Biology20: 144–51) reported an increase in the synonymity of mtDNA mutations (a sign of purifying selection) between pooled early-stage and late-stage PGCs. We re-analyzed Floros’ et al. pooled PGC data and noticed that their mutational dataset was significantly contaminated with single nucleotide variants (SNVs) derived from a nuclear sequence of mtDNA origin (NUMT) located on chromosome 5. Contamination was caused by co-amplification of the NUMT sequence by cross-specific PCR primers. Importantly,when we removed NUMT-derived SNVs, the evidence of purifying selection was abolished. In addition to pooled PGCs, Floros et al. reported the analysis ofsinglelate-stage PGCs, which were amplified with different sets of PCR primers that cannot amplify the NUMT sequence. Accordingly, we found no NUMT-derived SNVs among single PGCs mutations. Interestingly, single PGC mutations show adecreaseof synonymity with increased intracellular mutant fraction. This pattern is incompatible with predominantly negative selection. This suggests that germline selection of mtDNA mutations is a complex phenomenon and that the part of this process that takes place in PGCs may be predominantly positive. However counterintuitive, positive germline selection of detrimental mtDNA mutations has been reported previously and potentially may be evolutionarily advantageous.
Unraveling the role of non-coding rare variants in epilepsy
Authors: Girard Alexandre , Moreau Claudia , Michaud Jacques , Minassian Berge , Cossette Patrick , Girard Simon L. 
Published: December 2022

AbstractImportanceDespite the use of very large cohorts, the discovery of new variants has leveled off in recent years in epilepsy studies and consequently, most of the heritability is still unexplained. Rare non-coding variants have been largely ignored in studies on epilepsy, although non-coding single nucleotide variants can have a significant impact on gene expression.ObjectiveTo determine if rare non-coding deleterious variants are associated with epilepsy.DesignThis is a case-control study made possible by the CENet cohort.SettingThis was initially a multicenter study (families and trios), although the sequencing was processed at the same facility and for the present case-control study, only unrelated individuals were drawn.ParticipantsPatients used in this study are affected either by genetic generalized epilepsy (GGE), non-acquired focal epilepsy (NAFE) or are called ‘mixed’ (phenotype that differs from other affected relatives). Controls are unaffected parents from developmental and epileptic encephalopathy trios.Main Outcomes and MeasuresTo assess the functional impact of non-coding variants, ExPecto, a deep learning algorithm was used. A binomial logistic regression was performed to compare the burden of rare non-coding deleterious variants between cases and controls.ResultsWe had access to WGS from 123 GGE, 112 NAFE and 12 mixed for a total of 247 patients, as well as 377 controls. Rare non-coding highly deleterious variants were associated with GGE (OR 2.74; 95% CI 1.20-6.22), but not with NAFE (OR 0.85; 95% CI 0.27-2.67) or all epilepsy cases (OR 1.54; 95% CI 0.77-3.11) when compared with controls.Conclusion and RelevanceIn this study we showed that rare non-coding deleterious variants are associated with epilepsy, specifically with GGE. Larger WGS epilepsy cohort will be needed to investigate those effects at a greater resolution. Nevertheless, we demonstrated the importance of studying non-coding regions in epilepsy, a disease where new discoveries are scarce, and a high proportion of the heritability is yet to be explained.Key pointsQuestionAre non-coding single nucleotide variants (SNV) associated with epilepsy?FindingsIn this study we showed that patients with generalized genetic epilepsy (GGE) had significantly more rare non-coding deleterious variants than controls and non-acquired focal epilepsy (NAFE) patients. The study included 247 epilepsy patients and 377 controls who were sequenced for the whole genome.MeaningRare non-coding SNV are associated with epilepsy, more specifically with GGE.
A novel mechanistic framework for precise sequence replacement using reverse transcriptase and diverse CRISPR-Cas systems
Authors: Bill Kim Y. , Pierce Elizabeth B. , Brown Michael , Peterson Brenda A. , Sanford Derek , Fear Justin , Nicholl David , San Pedro Ellyce , Reynolds Grace M. , Hunt Joanne E. , Schwark David G. , Jali Sathya , Graham Nathaniel , Cesarz Zoe , Chapman Tracey A. Lincoln , Watts Joseph M. , Hummel Aaron W. 
Published: December 2022

ABSTRACTCRISPR/Cas systems coupled with reverse transcriptase (RT), such as the recently described Prime editing, allow for site-specific replacement of DNA sequences. Despite widespread testing of Prime editing, it is currently only compatible with type II CRISPR/Cas proteins such asStreptococcus pyogenesandStaphylococcus aureusCas9. Enabling RT compatibility with other CRISPR/Cas domains, such as type V enzymes with orthogonal protospacer adjacent motif specificities and smaller protein size would expand the range of edits that can be made in therapeutic and industrial applications. We achieve this with a novel mode of DNA editing at CRISPR-targeted sites that reverse transcribes the edit into the target strand DNA (e.g., the complement of the PAM-containing strand), rather than the non-target strand DNA, as in Prime editing. We term this technologyRNA encodedDNAreplacement ofalleleswith CRISPR (hereafter, REDRAW). We show that REDRAW extends the utility of RT-mediated editing beyond type II to include multiple type V CRISPR domains. REDRAW features a broad (8-10 bases) targeting window, at which all types of substitutions, insertions and deletions are possible. REDRAW combines the advantages of type V CRISPR domains with the extensive range of genetic variation enabled by RT-mediated, templated sequence replacement strategies.
Paternalism as a long-term strategy of a management control system
Authors: Cohanier Bruno , Baker Charles Richard 
Published: December 2022

PurposeThe purpose of this paper is to trace the evolution of paternalism as a long-term component of a management control system (MCS) in a multi-national business enterprise.Design/methodology/approachThe authors used a historical methodology involving the collection and evaluation of both primary and secondary data. Annual reports of Michelin (2009–2021) were also analysed to trace the evolution of the MCS towards corporate social responsibility (CSR).FindingsThis research traces the evolution of Michelin's Paternalistic MCS from “Traditional Paternalism” to “Welfare Paternalism”, “Managerial Paternalism” and “Libertarian Paternalism” thereby leading the way to CSR. The findings indicate that the evolution of the MCS revealed “Managerial Paternalism” as a specific type of paternalism and an important component of the “Personnel and Cultural Controls” (Merchant and Van der Stede, 2018, p. 95) at Michelin.Research limitations/implicationsMany multi-national companies began as family-owned and controlled firms (e.g. Ford, Toyota, Fiat, Renault, Tata) and they often employed paternalistic MCSs during their early development (Newby, 1977; Perrot, 1979; Colli, 2003). Such MCSs have been seen as being anachronistic and are often abandoned as the family-owned enterprise grows into a multi-national company (Casson and Cox, 1993; McKinlay et al., 2010). The research challenges this assertion and demonstrates how aspects of a paternalistic MCS can survive in a multi-national business enterprise.Practical implicationsWith respect to practical implications, this research shows that paternalism can still be a component of an MCS in a multi-national enterprise.Originality/valueUsing a historical approach, this research addresses a gap in the prior literature regarding the variations and persistence of paternalism in companies. In the case of Michelin, the authors investigate the evolution of its paternalistic MCS from a traditional form to an emphasis on CSR.
Pre-construction duration of public-private partnership projects: evidence from China
Authors: Wang Cong , Liu Henry , Sing Michael C.P. , Wu Jin 
Published: December 2022

PurposePre-construction of a project comprises stages that are pivotal for the procurement performance. It is defined as the duration from the project's initiation to construction. However, Private Public Partnerships (PPPs) have been subjected to a long pre-construction, thereby leading to an inefficient development process. Therefore, the purpose of this paper is to pay attention to the influencing factors elongating the pre-construction duration.Design/methodology/approachBased on data of 5,677 PPP projects between 2009 and 2021 in China, the authors adopt the Accelerated Failure Time (AFT) model in duration analysis to empirically analyze the following underlying dynamics determining the duration of PPP pre-construction stages: (1) policy uncertainty; (2) corruption; and (3) procurement method selection. To observe the influencing paths more specifically, the authors divided the pre-construction duration into the pre-tendering period and tendering period and regressed them separately.FindingsThe results indicate that the pre-construction duration is significantly prolonged with increased policy uncertainty and corruption degree as well as the use of tendering methods. Meanwhile, the above factors have a greater impact on the pre-tendering period than the tendering period.Originality/valueThe contribution of this study is twofold: (1) theoretically, this paper provides new evidence on the impact of PPP policy uncertainty, corruption and procurement method selection on the pre-construction duration. It complements empirical studies on the factors elongating the time efficiency of PPPs projects. (2) In practice, it provides a specific path for the government to improve the time efficiency of PPPs.
From corporate governance to sustainability outcomes: the key role of operations management
Authors: Sancha Cristina , Gutierrez-Gutierrez Leopoldo , Tamayo-Torres Ignacio , Gimenez Thomsen Cristina 
Published: December 2022

PurposeThis article studies the role played by sustainability operations management (OM) practices in the relationship between governance and environmental and social performance adopting the lenses of the upper echelons theory and the resource-based view. In particular, the authors study three main relationships: (1) the impact of governance on the implementation of sustainability OM practices, (2) the impact of sustainability OM practices on sustainability performance and (3) the mediating role of sustainability OM practices in the relationship between governance and sustainability performance.Design/methodology/approachTo test this study’s research model, the authors retrieved secondary data of 430 firms from the United Stated (US) and Europe and analyzed it using partial least squares (PLS)-based structural equation modeling (SEM).FindingsThis study’s results suggest that sustainability OM practices are needed to achieve higher social and environmental performance outcomes from governance, highlighting the key role of the OM department in the achievement of a sustainability strategy.Originality/valueThis paper adopts the environmental, social, governance (ESG) neglected focus and aims to provide a better understanding of and reveal the interrelationship between governance and sustainability OM practices (i.e. environmental and social).
A moderated-mediation model of the relationship between responsible leadership, citizenship behavior and patient satisfaction
Authors: Khanam Zeba , Tarab Sheema 
Published: December 2022

PurposeBased on the theory of planned behavior (TPB) and stakeholder theory, the model proposes that responsible leadership (RL) is mediated by affective commitment (AC) on both outcome variables (organizational citizenship behavior [OCB] and patient satisfaction [PS]) while distributive justice (DJ) moderates the relationship among RL, OCB and PS through the mediator of AC.Design/methodology/approachOverall, data collected from 275 employees and patients in India’s healthcare sector support this model both in online and offline mode. SPSS 25, AMOS 22 and PROCESS macro were used to analyze the data.FindingsThe influence of RL, OCB and PS was seen insignificant in the Indian healthcare sector. This study examines the role of AC as a mediator which does not affect extra-role behavior and PS. The findings also show that the moderation-mediation effect of DJ through AC strengthened the link between RL and OCB, but not PS. Commitment does not affect extra-role behavior and PS.Originality/valueUntil now, there has been no research in the Indian context that has tested the effect of RL on extra-role behaviors and PS, as mediated by AC, according to researchers’ knowledge. Since RL and outcome variables are related through AC, the current study aims to understand how DJ acts as a moderator to that relationship.
Marking-to-market IAS 37 provisions using options: an empirical demonstration
Authors: Haar Lawrence , Elharidy Ali , Gregoriou Andros 
Published: December 2022

Purpose
International Accounting Standards Rule 37 (IAS 37) for Contingent Liabilities and Assets were designed to make analysis of exposures facing a corporate entity easier to understand, but the rules may be insufficiently prescriptive making provisions inadequate predictors of potential outlays. The purpose of this research is to redress this problem. We apply financial option theory to objectively mark-to-market the appropriateness of provisions replacing subjective inputs with market derived calculations.

Design/methodology/approach
This study applies financial option theory to determine whether provisions are appropriate according to market data. This research supports inferences regarding the probability of a provision being used while evidencing scope for earnings management.

Findings
In addition to showing how IAS 37 provisions may be calibrated against market data, from the large sample of UK-listed companies, the proposition that over-provisioning is common and related to share price volatility, is supported, supporting the view that IAS 37 rules may facilitate earnings management.

Practical implications
The financial and reporting community have struggled in interpreting the appropriateness of IAS 37 provisions. Are they too large or too small? What is the probability they will be used? Using option theory and market data, various subjective judgements may now be validated. This research should have tangible value to analysts, auditors, investors and other stakeholders concerned in the accurate valuation of potential liabilities.

Originality/value
Replacing subjective judgement and insufficiently prescriptive guidance, this study shows that financial option theory and share price data may be used to objectively calibrate the size of IAS 37 provisions.
When does unrelated diversification increase performance? The effects of financial context and contingencies
Authors: Cerrato Daniele , La Rocca Maurizio , Alessandri Todd 
Published: December 2022

PurposeThe purpose of this paper is to examine the financial factors across multiple levels of analysis that influence the performance effects of the unrelated diversification strategy, including institutional-, industry- and firm-levels.Design/methodology/approachUsing a unique panel dataset of Italian firms from 1980 to 2010, the paper tests hypotheses on how industry external financial dependence and the firm's financial constraints both separately and jointly alter the performance benefits of unrelated diversification in contexts with financial market inefficiencies.FindingsUnrelated diversification increases performance in weak financial contexts and such positive effect is enhanced by greater industry external financial dependence and greater firm financial constraints. However, as financial markets develop, the moderating effects of firm financial constraints shrink.Practical implicationsThe study highlights the importance of recognizing the multiple financial contingencies that may alter the benefits of the unrelated diversification strategy, suggesting caution in its pursuit to boost firm performance.Originality/valueThe authors develop a theoretical framework that explains the performance outcomes of unrelated diversification, linking the benefits of an internal capital market (ICM) with the financial context of the firm and offering a fine-grained analysis that moves beyond the advanced/emerging economy dichotomy. Furthermore, leveraging on the unprecedented time frame of the empirical analysis, the paper highlights the crucial role of industry- and firm-level financial contingencies and demonstrates that their effects change at varying levels of development of the financial context.
Automated acoustic monitoring captures timing and intensity of bird migration
Authors: Van Doren Benjamin M. , Lostanlen Vincent , Cramer Aurora , Salamon Justin , Dokter Adriaan , Kelling Steve , Bello Juan Pablo , Farnsworth Andrew 
Published: December 2022

AbstractMonitoring small, mobile organisms is crucial for science and conservation, but is technically challenging. Migratory birds are prime examples, often undertaking nocturnal movements of thousands of kilometres over inaccessible and inhospitable geography. Acoustic technology could facilitate widespread monitoring of nocturnal bird migration with minimal human effort. Acoustics complements existing monitoring methods by providing information about individual behaviour and species identities, something generally not possible with tools such as radar. However, the need for expert humans to review audio and identify vocalizations is a challenge to application and development of acoustic technologies.Here, we describe an automated acoustic monitoring pipeline that combines acoustic sensors with machine listening software (BirdVoxDetect). We monitor 4 months of autumn migration in the northeastern United States with five acoustic sensors, extracting nightly estimates of nocturnal calling activity of 14 migratory species with distinctive flight calls. We examine the ability of acoustics to inform two important facets of bird migration: (1) the quantity of migrating birds aloft and (2) the migration timing of individual species. We validate these data with contemporaneous observations from Doppler radars and a large community of citizen scientists, from which we derive independent measures of migration passage and timing.Together, acoustic and weather data produced accurate estimates of the number of actively migrating birds detected with radar. A model combining acoustic data, weather and seasonal timing explained 75% of variation in radar‐derived migration intensity. This model outperformed models that lacked acoustic data. Including acoustics in the model decreased prediction error by 33%. A model with only acoustic information outperformed a model comprising weather and date (57% vs. 48% variation explained, respectively).Acoustics also successfully measured migration phenology: species‐specific timing estimated by acoustic sensors explained 71% of variation in timing derived from citizen science observations.Synthesis and applications. Our results demonstrate that cost‐effective acoustic sensors can monitor bird migration at species resolution at the landscape scale and should be an integral part of management toolkits. Acoustic monitoring presents distinct advantages over radar and human observation, especially in inaccessible and inhospitable locations, and requires significantly less expense. Managers should consider using acoustic tools for monitoring avian movements and identifying and understanding dangerous situations for birds. These recommendations apply to a variety of conservation and policy applications, including mitigating the impacts of light pollution, siting energy infrastructure (e.g. wind turbines) and reducing collisions with structures and aircraft.
Pollinator predation stabilizes plant–pollinator mutualisms through the modification of pollinator behavior
Authors: Kawata Shohei , Takimoto Gaku 
Published: December 2022

AbstractMutualisms are a basic component of multispecies communities and play crucial roles in the functioning of ecosystems. Early theory on mutualisms, however, predicted that mutualistic interactions could be destabilizing because the interdependent augmentation of mutualists caused their population explosion. Later studies suggested that additional factors, such as costs or saturating benefits of mutualisms and antagonistic interactions that exploited mutualisms, could dampen the destabilizing effect of mutualisms. In plant–pollinator mutualisms, predation on pollinators is a common form of antagonistic interactions, although its effects on the stability of plant–pollinator mutualisms have remained poorly understood. Here, using a mathematical model, we consider whether predation on pollinators can stabilize plant–pollinator mutualisms. We show that predation on pollinators does not stabilize an inherently unstable plant–pollinator mutualism, but the modification of pollinator behavior to avoid predation can stabilize the mutualism. Our results contribute to a better understanding of how predator‐induced behavior modification in pollinators can affect the maintenance of plant–pollinator mutualisms.