bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss-of-function coding variants in the Ras of Complex Proteins/GTPase domain of Leucine Rich Repeat Kinase 2
Authors: Butterfield Sarah , Herbst Susanne , Lewis Patrick Alfryn 
Published: December 2024

AbstractTheLRRK2gene is a key contributor to genetic risk of Parkinson’s disease, and a priority drug target for the disorder. Leucine Rich Repeat Kinase 2, the protein product ofLRRK2, is a multidomain enzyme implicated in a range of cellular processes – including endolysosomal trafficking and damage response. Based on the report that truncation and structural variants resulting in loss of LRRK2 protein are observed in human populations, genomic sequence repositories were queried for coding variants affecting key catalytic residues in LRRK2 – resulting in the identification of three variants (K1374E, K1374R, and T1348P) predicted to ablate the capacity of LRRK2 to bind GTP. Biochemical and cellular characterization of these variants confirmed loss of GTP binding, as well as reduced or loss of kinase activity. These data demonstrate the presence of rare coding enzymatic loss-of-function variants in humans, with implications for our understanding of LRRK2 as a driver of disease and as a drug target.
One-Size-Fits-Many: Antisense oligonucleotides for rescuing splicing mutations in hotspot exons
Authors: Duan Chaorui , Rong Stephen , Buerer Luke , Neil Christopher R. , Savatt Juliann M. , Strande Natasha T. , Fairbrother William G. 
Published: December 2024

ABSTRACTMutations that impact splicing play a significant role in disease etiology but are not fully understood. To characterize the impact of exonic variants on splicing in 71 clinically-actionable disease genes in asymptomatic people, we analyzed 32,112 exonic mutations from ClinVar and Geisinger MyCode using a minigene reporter assay. We identify 1,733 splice-disrupting mutations, of which the most extreme 1-2% of variants are likely to be deleterious. We report that these variants are not distributed evenly across exons but are mostly concentrated in the ∼8% of exons that are most susceptible to splicing mutations (i.e. hotspot exons). We demonstrate that splicing defects in these exons can be reverted by ASOs targeting the splice sites of either their upstream or downstream flanking exons. This finding supports the feasibility of developing single therapeutic ASOs that could revert all splice-altering variants localized to a particular exon.
Structural MRI Differences Between Parkinson’s Disease Motor Subtypes in Early-Stage: A Multicontrast Imaging Study
Authors: Bispo Diógenes Diego de Carvalho , Neto Edinaldo Gomes de Oliveira , Brandão Pedro Renato de Paula , Pereira Danilo Assis , Grippe Talyta Cortez , Maluf Fernando Bisinoto , Regattieri Neysa Aparecida Tinoco , Faria Andreia , Li Xu , Tavares Maria Clotilde Henriques , Cardoso Francisco Eduardo Costa 
Published: December 2024

ABSTRACTBackgroundParkinson’s disease (PD) is characterized by dopaminergic neuron degeneration, leading to motor and neuropsychological symptoms. PD is clinically divided into tremor-dominant (TD) and postural instability-gait disorder (PIGD) subtypes, which may differ in neuroanatomical changes. Neuroimaging explores these differences, enhancing understanding of PD heterogeneity.ObjectivesThis study examines neuroanatomical differences between subtypes using MRI, focusing on subcortical volumes, cortical thickness, iron deposition, and white matter changes.MethodsThis cross-sectional study included 51 PD patients and controls. Participants underwent clinical assessments and MRI. Cortical and subcortical segmentation was automated using FreeSurfer, and quantitative susceptibility mapping was used to assess brain iron content. Diffusion-weighted MRI data were processed using Tractseg for tractometry analysis.ResultsThe PD-TD group exhibited higher iron levels in the substantia nigra compared to healthy controls. Iron deposition in the thalamus correlated with MDS-UPDRS-part-III and PIGD scores. Tractometry showed differences in fractional anisotropy (FA) between PD-TD and PD-PIGD in the bilateral fronto-pontine tract (FPT). The PD-PIGD group had decreased FA in the middle cerebellar peduncle (MCP) compared to controls. FA in the left FPT correlated with tremor scores, while FA in the MCP correlated with PIGD scores.ConclusionsThis study highlights distinct neuroimaging signatures between PD motor subtypes. Elevated iron deposition in the substantia nigra is a shared feature, particularly in the TD subtype. Subtype-specific white matter changes, including reduced FA in the FPT and MCP, correlate with tremor and PIGD scores. These findings underscore the potential of neuroimaging biomarkers in unraveling PD heterogeneity and guiding tailored approaches.
Degron-modified Cas12a enhances single-cell CRISPR screening
Authors: Snetkova Valentina , Galan Carolina , Lopez Romain , Rios Antonio R. , Kudo Takamasa , Dorighi Kristel , Warming Søren , Haley Benjamin J. 
Published: December 2024

AbstractSingle-cell CRISPR (Perturb-seq) screens have primarily relied on Cas9 whereas Cas12a, despite its unique effectiveness for multiplex guide expression, remains underexplored. This may be due to Cas12a’s guide RNA array (pre-crRNA) self-processing activity and the subsequent challenges associated with pre-crRNA sequence recovery. By developing modified pre-crRNA expression vectors and a degron-based Cas12a system, we overcome the self-processing constraint, allowing for accurate detection of pre-crRNAs at the single-cell level, thus greatly expanding possibilities for future Perturb-seq efforts.
Degradation of LMO2 in T cell leukaemia causes collateral breakdown of transcription complex partners and LMO2-dependent apoptosis
Authors: Sereesongsaeng Naphannop , Bataille Carole J.R. , Russell Angela J. , Bery Nicolas , Sialana Fernando , Choudhary Jyoti , Miller Ami , Rabbitts Terry H. 
Published: December 2024

ABSTRACTLMO2 is a transcription factor activated by chromosomal translocations or promoter mutations in T cell leukaemia. It forms part of a multiprotein complex that has bipartite DNA binding through heterodimeric TAL1/SCL-E47 bHLH and GATA proteins. LMO2 is an intrinsically disordered protein and difficult to study in its cellular environment. A chimaeric intracellular antibody has been developed fusing an anti-LMO2 single domain variable region with one of three E3 ligases to create biodegrader tools. The intracellular binary interaction of these biodegraders with LMO2 leads to its proteosomal degradation but, in addition, we observe concomitant loss of TAL1/SCL and E47 bHLH proteins that associate with LMO2 in the DNA-binding complex. Chemical compound surrogates of the intracellular antibody paratope (called Abd compounds) have been modified to create proteolysis targeting chimaeras (PROTACs). These form a ternary complex with LMO2 and E3 ligase in leukaemia cells that induces degradation of LMO2, accompanied by loss of TAL1/SCL and E47, T-ALL growth inhibition and instigation of apoptosis. The compounds have potential for LMO2 dependent drug development and our Abd technology is a potential approach for the drug development for targeting transcription factors and intrinsically disordered proteins.
The incubation revolution: transforming entrepreneurial education with artificial intelligence
Authors: Thottoli Mohammed Muneerali , Cruz Maria Elisa , Al Abri Salem Said Salem 
Published: December 2024

Purpose
Universities face challenges due to the absence of artificial intelligence (AI) integration in entrepreneurship education (EE) and its incubation centers for young startups. Making a business plan for their innovative enterprises, which includes market analysis, financial projections, marketing strategy and an operations plan, are a few of the toughest tasks they may face. Aspiring students can make it simple to launch their dream business by integrating AI tools. Hence, this study aims to conduct a systematic literature review (SLR) to examine the global trend of the transformation of EE with AI and determine the necessity of integrating AI in university incubation centers as a potential future research direction.

Design/methodology/approach
In this study, the authors conducted an SLR method to investigate the transformation of EE with AI. This review employed a bibliometric analysis covering the period of 1993–2023 and utilized articles published in scientific journals available in the SCOPUS database as our data source.

Findings
There is an enormous potential for research on EE using cutting-edge AI in developed and developing nations. There is a lack of studies exploring AI integration into university incubation centers. Hence, there are possible future directions for research into integrating AI into university incubation centers using cutting-edge tools like chatbots, ChatGPT, ChatGen and other AI that will help to develop a comprehensive business plan for students aspiring entrepreneurial venture startups.

Research limitations/implications
The study’s research was limited using the Scopus database’s core collection, which may ignore other significant research articles. Therefore, the study’s scope can be constrained due to the narrow search parameters. The study, however, tries to establish the importance of its research by offering a thorough review and evaluation of AI in EE.

Practical implications
There is significance of incorporating AI into EE to foster an EE culture and realize its potential benefits. To transform incubation centers and promote aspirant entrepreneurs in the fourth industrial revolution (4IR), higher education institutions (HEIs) should strategically adopt AI.

Originality/value
This study presents a novel viewpoint by investigating the distinction in AI perception and usage among educators, advocating the incorporation of AI in university incubation centers to help entrepreneurial students. It contributes uniqueness and innovative approaches to early startup issues in EE.
ESG strategies and corporate financial performance: a comparison of the US energy and renewable energy industries
Authors: Hyusein Ayshe , Cek Kemal 
Published: December 2024

Purpose
This study aims to investigate the relationship between environmental, social and governance (ESG) strategies and corporate financial performance in energy and renewable energy industries in the USA between 2013 and 2023.

Design/methodology/approach
The system generalised method of moments technique analyses the annual panel data at the given period. LSEG Asset 4 Database (formerly Thompson and Reuters) scores were used to measure ESG and corporate financial performance scores via accounting and market-based performance.

Findings
The results show that energy and renewable energy companies cannot be categorised as individual industries and that there is no difference between the two. Energy industry findings reveal that ESG strategies were positively associated with accounting performance and negatively related to market performance. Both environmental and governance pillars had insignificant and social pillar had positive effects on accounting performance, whereas only the environmental pillar negatively affected market performance.

Originality/value
The findings have unique implications for companies investing in ESG strategies in the US energy industry. They also suggest a direction for formulating compulsory regulations in the US energy industry, which can be valuable for policymakers, governments and financial regulators in shaping the industry’s future and potentially influencing its trajectory.
National innovation system for resilience, transformation and sustainable development in Uganda: contextual analysis of the factors, actors and associated linkages
Authors: Jjagwe Ronald , Kirabira John Baptist , Mukasa Norbert , Okure Mackay 
Published: December 2024

Purpose
While the role of the National Innovation System (NIS) in promoting economic growth is well recognized, there remains a significant knowledge gap concerning how interactions among actors and learning processes within these systems facilitate innovation commercialization in Uganda. This gap hinders the effective design and implementation of policies aimed at boosting innovation-driven development in emerging economies. This study aims to explore the linkages and interrelationships among NIS actors in Uganda.

Design/methodology/approach
This study used systematic document reviews and case-study techniques. A systematic review based on the SPAR-4-SLR protocol evaluated the literature on Uganda’s NIS, including policy and strategy documents, development frameworks, journal articles and working papers. This dual approach allowed for an in-depth analysis of policy documents and empirical examples, revealing complex mechanisms within Uganda’s NIS. A content analysis tool facilitated the reduction of qualitative data through codification, theme development and the reporting of results.

Findings
This study explored the relationships among NIS actors, offering insights into using Uganda’s unique institutional and economic landscape for sustainable growth. It identifies key drivers, such as improved collaboration between the government, industry and academia and strategic policy measures in technology transfer and innovation funding, which are essential for revitalizing Uganda’s innovation ecosystem.

Research limitations/implications
This study presents a preliminary analysis of Uganda’s NIS. Future studies should adopt a longitudinal approach to examine the evolution of NIS over time, including the impact of global technological advancements and policy changes on Uganda’s innovation ecosystem. To elucidate the complex interrelationships within an NIS, subsequent research could employ network analysis or systems thinking methodology. These approaches would facilitate a more nuanced understanding of the interconnections and reciprocal influences among various NIS stakeholders.

Practical implications
The inclusion of the innovation, technology development and transfer (ITDT) program in National Development Plan III demonstrates that National Innovation System (NIS) incorporation into the country’s development process is possible through a combination of policy/regulatory, market/economic and technical/technological factors.

Originality/value
This study significantly advances the understanding of innovation systems by detailing the intricate network of relationships within Uganda’s NIS. This highlights the unexplored dimensions of learning and cooperation and offers a thorough analysis of the factors that enable innovation, which are crucial for promoting innovation in a developing country.
Achieving resilient supply chains: managing temporary healthcare supply chains during a geopolitical disruption
Authors: Duong Linh , Sanderson Helen S. , Phillips Wendy , Roehrich Jens K. , Uwalaka Victor 
Published: December 2024

PurposeGeopolitical disruptions significantly impact the management of temporary healthcare supply chains (HSCs). Common across geopolitical disruptions is the interruption to the flow of supplies, calling for organizations to reconfigure their existing supply chains or set up temporary ones. We theoretically and empirically investigate how temporary HSCs are designed to ensure a resilient flow of vital healthcare products during a geopolitical disruption.Design/methodology/approachWe investigated two different temporary HSCs – potable water and blood products – that experienced geopolitical disruptions. We purposefully sampled HSCs in deployed medical care where healthcare providers operate in resource-austere, politically volatile environments and timing and access to specialist expertise, medical equipment and medicines are critical. We built on rich datasets, including archival data, 12 expert workshops and 41 interviews.FindingsThe nature of temporary HSCs (e.g. urgency of demand and time-limited need) and product characteristics (e.g. perishability and strict storage conditions) lead to complexity in designing resilience for temporary HSCs. In contrast to permanent supply chains, temporary HSCs have limited flexibility and redundancy. Collaboration and agility are predominant strategies for enhancing resilience for temporary HSCs.Practical implicationsThe study uncovers an urgent need for radical changes in how managers and policymakers responsible for HSC address resilience. During geopolitical disruptions, managers and policymakers need to review healthcare regulations across nations and prioritize by activating high levels of information- and knowledge-sharing between nations.Originality/valueThis study addresses an underresearched area of investigation by theoretically combining and empirically investigating the supply chain strategies employed by organizations to build up resilience in temporary HSCs.
Fiscal support and the impacts of tumbling oil prices from COVID-19 on MENA’s economy, energy consumption and environment
Authors: Khalilnezhad Zahra , Eslamloueyan Karim 
Published: December 2024

Purpose
This study aims to investigate the impact of the oil crash during the COVID-19 pandemic on the economy, energy and the environment in MENA countries, with and without fiscal policy, in a global context.

Design/methodology/approach
This study applies a Global Vector Autoregressive (GVAR) model for 47 countries from 2006Q1 to 2021Q3. The sign restriction method is used to identify the oil shocks originating from the COVID-19 crisis.

Findings
Empirical evidence shows that without fiscal interventions, MENA countries experienced a decline in output growth, energy consumption and CO2 emissions due to lower oil prices caused by the COVID-19 pandemic. The impact of the oil price shock on inflation varied across the region. Economic growth and inflation rates in MENA countries turn positive when the member states implement expansionary fiscal measures to stimulate economic activities during the pandemic. Hence, fiscal policy played a crucial role in supporting the economy and preventing a severe recession during COVID-19 in the MENA region. However, expansionary fiscal measures increased energy consumption and air pollution.

Practical implications
The findings help policymakers better cope with the outbreak of deadly pandemics in the coming years. It improves our understanding of the role of fiscal policy in boosting economic efforts and reducing the adverse environmental impact of increased government spending.

Originality/value
This paper enhances the current body of literature by investigating how fiscal policies implemented by the MENA countries help mitigate the adverse economic effects of the COVID-19 crisis. Moreover, it enables us to analyze the impact of fiscal support on energy consumption and the environment during an oil shock influenced by global uncertainty, lockdowns, and supply chain disruptions.
Modelling the mass adoption potentials of fashion-augmented reality among the young consumers: evidence from an emerging economy
Authors: Akther Mohima , Reza Mohammad Nurul Hassan , Al Mamun Abdullah , Aziz Norzalita Abd , Yang Marvello 
Published: December 2024

PurposeThe increasing demand for fashion-augmented reality (FAR) in online fast fashion shopping has the potential to reduce soil and water pollution. Hence, it is vital to understand the success factors that influence consumers’ intention to use FAR (IAR) and actual usage of FAR (UAR) to enhance its adoption.Design/methodology/approachBy incorporating the unified theory of acceptance and use of technology, this study examined the influence of success factors on IAR, the effect of IAR on UAR and the mediating role of IAR in the relationship between success factors and UAR. In total, 803 responses were collected from Indonesia using a cross-sectional approach. Data were examined using partial least squares structural equation modelling.FindingsTheir findings revealed that perceived enjoyment, perceived service value and facilitating conditions significantly influenced IAR and UAR. However, the impacts of perceived functional benefits, lifestyle compatibility and perceived trust were insignificant. Nevertheless, the IAR has a significant influence on UAR. Finally, the IAR mediates the relationships among perceived enjoyment, perceived service value, facilitating conditions and UAR.Research limitations/implicationsThis study provides valuable insights for practitioners to develop marketing strategies and improve consumer perceptions of FAR, particularly in emerging economies. One limitation of this study is that it exclusively examined young consumers and restricted the examination to specific aspects of consumer behaviour.Originality/valueIntegrating the unified theory of acceptance and use of technology and partial least squares structural equation modelling provides a comprehensive understanding of the underlying dynamics and sheds light on the success factors that drive consumer IAR into UAR and contribute to Sustainable Development Goal 12 by reducing soil and water pollution.
Lean healthcare: a science mapping of current progress and future research avenues
Authors: Nawanir Gusman , Fauzi Muhammad Ashraf 
Published: December 2024

PurposeThis study intends to reveal the existing research stream and predict future research avenues for lean healthcare (LH). This paper analyzes the progress of LH research and identifies key trends, research gaps and future directions. By mapping the knowledge structure, the study offers insights into the effects of LH on healthcare efficiency, patient care and organizational performance.Design/methodology/approachThe review used the bibliometric approach, involving 319 journal articles retrieved from the Web of Science database. Two science mapping approaches (i.e. bibliographic coupling and co-word analysis) were performed to investigate the current knowledge structure and future research direction in LH.FindingsThe current research trend in LH focuses on developing frameworks and strategic implementation by considering critical determinants and decision-making strategies. In the future, the research on LH will emphasize the holistic frameworks and efficient strategies for healthcare excellence, along with strategies to overcome barriers to its implementation.Research limitations/implicationsThis study will benefit researchers and practitioners by advancing their understanding and applying LH principles.Originality/valueThis study provides valuable practical implications for healthcare managers to navigate the complexities of lean implementation, optimize processes and drive sustainable improvements in the healthcare context.