bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of DXS as an attractive drug target in mycobacteria
Authors: Maila T , Nicolaai M , Mbau R.D , Mashabela G.T.M 
Published: November 2024

AbstractA rapid emergence in the incidences of Tuberculosis (TB) drug resistance undermines efforts to eradicate the disease and strengthens calls for development of new drugs with novel mechanisms of action. In drug discovery, finding an attractive drug target is as important as finding a good drug candidate. Hence more efforts are made to identify, validate and prioritize drug targets in TB drug discovery. Here, using CRISPRi technology, we showed thatdxs1transcriptional knockdown attenuated growth of bothMycobacterium smegmatisandMycobacterium tuberculosiscultures, and the effect was more profound in the latter. Chemical supplementation of the growth medium with 10 μM of isoprenoid pyrophosphates, thiamine and thiamine pyrophosphate failed to rescue growth ofM. smegmatiscultures, while partial rescue was observed with addition of menatetrenone, a menaquinone derivative with four isoprenyl groups. Similarly, culture growth could not be rescued by the addition of prenol and isoprenol, which suggested the lack of isoprenoid salvage pathway in mycobacteria. Importantly, and in the context of drug discovery,dxs1depleted mutants displayed four-fold more sensitive towards a mixture of isoniazid, rifampicin and ethambutol, suggesting that inhibitors of DXS enzyme or other MEP pathway enzymes could potentiate antimycobacterial effect of the first-line TB drugs. Additionally,dxs1depletion increased growth retardation of the mutant in acidic pH and under oxidative stress, conditions that are encountered in activated macrophage compartments. Taken together, our results validated DXS as an attractive drug target that should be prioritized for developments on new antitubercular agents.
Nucleus accumbens D2-expressing neurons: Balancing reward and licking disruption through rhythmic optogenetic stimulation
Authors: Requejo-Mendoza Nikte , Arias-Montaño José-Antonio , Gutierrez Ranier 
Published: November 2024

AbstractDopamine D1 receptor-expressing neurons in the nucleus accumbens (NAc) are known to be critical for processing reward and regulating food intake. However, the role of D2-expressing neurons in this region remains less understood. This study employed optogenetic manipulations to investigate the role of NAc D2-expressing neurons in reward processing and sucrose consumption. Optogenetic activation of these neurons decreased sucrose preference (at 20 Hz), disrupted licking patterns (particularly at 8 and 20 Hz), and increased self-stimulation. Conversely, synchronizing stimulation with the animal’s licking rhythm mitigated licking disruption and even increased sucrose intake, suggesting a rewarding effect. Furthermore, 20 Hz stimulation (but not 8 Hz) induced place preference in a real-time place preference (RTPP) test. In contrast, inhibiting D2 neurons produced a negative hedonic state, although not reaching a complete aversion, influencing food choices in specific contexts. For instance, while the RTPP test per se was not sensitive enough to observe place aversion when mice could choose between consuming a high-fat diet (HFD) pellet in a context associated with or without inhibition of D2 neurons, they preferred to consume HFD on the non-inhibited side. This suggests that the palatability of HFD can unmask (but also overshadow) the negative hedonic state associated with D2 neuron inhibition. A negative reinforcement paradigm further confirmed the active avoidance behavior induced by D2 neuron inhibition. In conclusion, NAc D2 neuron inhibition induces a negative hedonic state, while activation has a dual effect—it is rewarding yet disrupts licking behavior—highlighting its complex role in reward and consummatory behavior. Importantly, self-paced stimulation, where the animal controls the timing of the stimulation by its licking behavior, offers a more efficient and natural approach for stimulating NAc activity.
A rare HSC-derived megakaryocyte progenitor accumulates via enhanced survival and contributes to exacerbated thrombopoiesis upon aging
Authors: Manso Bryce A. , Medina Paloma , Smith-Berdan Stephanie , Rodriguez y Baena Alessandra , Bachinsky Elmira , Mok Lydia , Deguzman Angela , Avila Sarah Beth , Chattopadhyaya Saran , Rommel Marcel G.E. , Jönsson Vanessa D. , Forsberg E. Camilla 
Published: November 2024

AbstractDistinct routes of cellular production from hematopoietic stem cells (HSCs) have defined our current view of hematopoiesis. Recently, we challenged classical views of platelet generation, demonstrating that megakaryocyte progenitors (MkPs), and ultimately platelets, can be specified via an alternate and additive route of HSC-direct specification specifically during aging. This “shortcut” pathway generates hyperactive platelets likely to contribute to age-related platelet-mediated morbidities. Here, we used single-cell RNA/CITEseq to demonstrate that these age-unique, non-canonical (nc)MkPs can be prospectively defined and experimentally isolated from wild type mice. Surprisingly, this revealed that a rare population of ncMkPs also exist in young mice. Young and aged ncMkPs are functionally distinct from their canonical (c)MkP counterparts, with aged ncMkPs paradoxically and uniquely exhibiting enhanced survival and platelet generation capacity. We further demonstrate that aged HSCs generate significantly more ncMkPs than their younger counterparts, yet this is accomplished without strict clonal restriction. Together, these findings reveal significant phenotypic, functional, and aging-dependent heterogeneity among the MkP pool and uncover unique features of megakaryopoiesis throughout life, potentially offering cellular and molecular targets for mitigation of age-related adverse thrombotic events.
Biochemical evidence for the diversity of LHCI proteins in PSI-LHCI from the red algaGaldieria sulphurariaNIES-3638
Authors: Nagao Ryo , Ogawa Haruya , Suzuki Takehiro , Dohmae Naoshi , Kato Koji , Nakajima Yoshiki , Shen Jian-Ren 
Published: November 2024

AbstractRed algae are photosynthetic eukaryotes whose light-harvesting complexes (LHCs) associate with photosystem I (PSI). In this study, we examined characteristics of PSI-LHCI, PSI, and LHCI isolated from the red algaGaldieria sulphurariaNIES-3638. The PSI-LHCI supercomplexes were purified using anion-exchange chromatography followed by hydrophobic interaction chromatography, and finally by trehalose density gradient centrifugation. PSI and LHCI were similarly prepared following the dissociation of PSI-LHCI with Anzergent 3-16. Polypeptide analysis of PSI-LHCI revealed the presence of PSI and LHC proteins, along with a red-lineage chlorophylla/b-binding-like protein (RedCAP), which is distinct from LHC proteins within the LHC protein superfamily. RedCAP, rather than LHC proteins, exhibited tight binding to PSI. Carotenoid analysis of LHCI identified zeaxanthin,β-cryptoxanthin, andβ-carotene, with zeaxanthin particularly enriched, which is consistent with other red algal LHCIs. A Qy peak of chlorophyllain the LHCI absorption spectrum was blue-shifted compared with those of PSI-LHCI and PSI, and a fluorescence emission peak was similarly shifted to shorter wavelengths. Based on these results, we discuss the diversity of LHC proteins, including RedCAP, in red algal PSI-LHCI supercomplexes.
Comparative Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease Subtypes in theAll of UsResearch Program
Authors: Smith Johanna L. , Norland Kristjan , Hamed Marwan E. , Yu Yue , Na Jie , Dikilitas Ozan , Schaid Daniel J. , Kullo Iftikhar J. 
Published: November 2024

AbstractBackgroundPerformance and portability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease (ASCVD) phenotypes vary based on different methods, training data, and trait ascertainment.ObjectivesWe aimed to investigate performance and portability of contemporary PRS for ASCVD subtypes: coronary heart disease (CHD), abdominal aortic aneurysm (AAA), ischemic stroke (IS), and peripheral artery disease (PAD), using theAll of UsWorkbench which provides access to a large diverse cohort with phenotype and whole genome sequence data. We also developed and evaluated a multi-trait PRS for each subtype.MethodsPerformance of PRS for 4 ASCVD traits and related risk factors was compared across genetic ancestry groups in 245,388All of Usparticipants. Genetic EUR, African (AFR), Admixed American (AMR), and remaining ancestry groups (combined as Other, OTH) were defined byAll of Usbased on principal components. PRS for CHD, IS, AAA, PAD, and multi-trait (combining PRS for the 4 traits as well as PRS for ASCVD risk factors) were assessed for portability across genetic ancestry groups using hazard ratios (HR) per SD increase.ResultsFor CHD, CHDPGS003725performed the best (HR for 1 SD increase [95% CI]), across 4 genetic ancestry groups (EUR: 1.72[1.67-1.78], AFR: 1.24[1.18-1.31], AMR: 1.48[1.37-1.59], OTH: 1.65[1.52-1.79]). The best performing PRS for AAA was AAAPGS003972(EUR: 1.68[1.59-1.78], AFR: 1.29[1.13-1.48], AMR: 1.30[1.06-1.60], OTH: 1.45[1.20-1.75]). The best performing IS PRS was ISPGS000039in AFR (1.12[1.06-1.17]), AMR (1.11[1.04-1.19]), and OTH (1.23[1.09-1.38]), and ISPGS004939in EUR (1.16[1.12-1.20]). For PAD, PADPGS004940performed best in EUR (1.26[1.22-1.30]), AFR (1.11[1.05-1.18]), AMR (1.08[1.01-1.16]), and OTH (1.13[1.04-1.22]). Multi-trait PRS performed better than individual trait PRS for each ASCVD phenotype. Also, PRS derived from multi-ancestry cohorts performed better than those derived from single ancestry.ConclusionsPRS for ASCVD developed from multi-ancestry cohorts and multiple related traits performed best across ancestrally diverse and admixed individuals. PRS for CHD and AAA performed better than those for IS and PAD.
Intersectional consequences for marginal fairness in prediction models for emergency admissions
Authors: Lett Elle , Shahbandegan Shakiba , Barak-Corren Yuval , Fine Andy , La Cava William G. 
Published: November 2024

AbstractBackgroundFair clinical prediction models are crucial for achieving equitable health outcomes. Recently, intersectionality has been applied to develop fairness algorithms that address discrimination among intersections of protected attributes (e.g., Black women rather than Black persons or women separately). Still, the majority of medical AI literature applies marginal de-biasing approaches, which constrain performance across one or many isolated patient attributes. We investigate the extent to which this modeling decision affects model equity and performance in a well-defined use case in emergency medicine.MethodsThe study focused on predicting emergency room admissions using electronic health record data from two large U.S. hospitals, Beth Israel Deaconess Medical Center (MIMIC-IV-ED, n=160,016) and Boston Children’s Hospital (BCH, n=22,222), covering both adult and pediatric populations. In a comprehensive experiment over fairness definitions, modeling methods, we compared the performance of single- and multi-attribute, marginal de-biasing approaches to intersectional de-biasing approaches.ResultsIntersectional de-biasing produces greater reductions in subgroup calibration error (MIMIC- IV: 21.2%; BCH: 27.2%) than marginal de-biasing (MIMIC-IV: 10.6%; BCH: 22.7%), and also lowers subgroup false negative rates on MIMIC-IV an additional 3.5% relative to marginal de-biasing. These fairness gains were achieved without a significant decrease in model accuracy between baseline and intersectionally-debiased models (MIMIC-IV: AUROC=0.85±0.00, both models; BCH: AUROC=0.88±0.01 vs 0.87±0.01). Intersectional de-biasing more effectively lowered subgroup calibration error and FNRs in low-prevalence groups in both datasets compared to other de-biasing conditions.ConclusionIntersectional de-biasing better mitigates performance disparities across intersecting groups compared to marginal approaches for emergency admission prediction. These strategies meaningfully reduce group-specific error rates without compromising overall accuracy. These findings highlight the importance of considering interacting aspects of patient identity in model development, and suggest that intersectional de-biasing would be a promising gold standard for ensuring equity in clinical prediction models.
The 5-methylcytosine DNA glycosylase ROS1 antagonizes parent-of-origin specific DNA methylation in Arabidopsis endosperm
Authors: Hemenway Elizabeth A. , Gehring Mary 
Published: November 2024

AbstractDNA methylation patterning is a consequence of opposing activities of DNA methyltransferases and DNA demethylases. In flowering plants, two distinct female gametes, the egg cell and the central cell, are fertilized, producing what will become the embryo and the endosperm of the seed. In Arabidopsis, a 5-methylcytosine DNA glycosylase, DME, demethylates regions in the central cell genome, leading to methylation differences between maternally- and paternally-inherited endosperm genomes after fertilization.DMEis required for endosperm gene imprinting. Homologues ofDMEincludeROS1,DML2andDML3. It is unknown whether any of these DNA glycosylases are required for endosperm methylation patterning. We show thatROS1prevents hypermethylation of paternally-inherited alleles in the endosperm at regions that lack maternal or paternal-allele methylation in wild-type. Thus,ROS1promotes epigenetic symmetry between genomes in the endosperm by preventing paternal genome hypermethylation. We propose thatROS1andDMEact in a parent-of-origin-specific manner at shared endosperm targets, and consider implications for the evolution of imprinting mechanisms.
The value-relevance of gains on bargain purchase: do actions speak louder than words?
Authors: Badenhorst Wessel M. 
Published: November 2024

PurposeThis paper investigates whether disclosure quality and a history of overpaying for acquisitions are associated with differences in the value-relevance of gains on bargain purchase with high disclosure prominence.Design/methodology/approachFindings are from multivariate regression results, using a sample of firms listed in South Africa from 2010 to 2019, where a mandatory earnings reconciliation provides high disclosure prominence for gains on bargain purchase.FindingsGiven high disclosure prominence, disclosure quality is not associated with differences in the pricing of gains on bargain purchase. Instead, most gains on bargain purchase are priced as future losses (unrecognised liabilities). However, when a firm has a history of overpaying for acquisitions, gains on bargain purchase are priced as transitory economic gains.Research limitations/implicationsFurther research is required to determine if overpaying for acquisitions similarly communicates the credibility of gains on bargain purchase when disclosure prominence is low.Practical implicationsDisclosure prominence can reduce disclosure processing costs and increase the value-relevance of complex acquisition accounting. High disclosure quality cannot compensate for a weak acquisition track record.Originality/valueFindings deepen our understanding of the pricing of gains on bargain purchase. This paper presents empirical results that reconcile previously conflicting theoretical views of gains on bargain purchase (as unrecognised assets or as unrecognised liabilities), by shedding light on the role that a record of overpaying for acquisitions plays in the value-relevance of gains on bargain purchase.
Digital technologies and social sustainability in the digital transformation age: a systematic analysis and research agenda
Authors: Qadri Usman Ahmad , Ghani Mazuri Binti Abd , Abbas Ulfat , Kashif Abdul Rauf 
Published: November 2024

Purpose
This paper aims to systematically review the constructive effects of digital transformation (DT) on social sustainability, examining its impact across democracy and governance, social cohesion, quality of life, equality and diversity. It emphasizes the need for appropriate frameworks that incorporate DT strategies in organizational practices to improve social sustainability.

Design/methodology/approach
A systematic literature review was carried out through Web of Science and Scopus databases to identify the distinctive papers that explored the impact of DT on social sustainability. It analyzes how various digital technologies, like Internet of Things, cloud computing and mobile computing, can be strategically embedded in organizational practices to optimize social sustainability outcomes.

Findings
This study reveals that although DT significantly enhances operational capabilities and consumer experiences, its integration into social sustainability practices is often overlooked. It proposes a novel framework that aligns digital capabilities with sustainability goals, aiming to enrich organizational performance and societal welfare. This paper identifies dynamic capabilities as crucial for sustaining competitive advantage in a digitally transformed business landscape.

Research limitations/implications
The primary limitation is the reliance on secondary data, which may not fully capture the rapid advancements in DT. Future research should focus on empirical studies to validate the proposed framework and explore the dynamic capabilities required for integrating DT in social sustainability practices.

Originality/value
This study extends the discourse on DT by linking it explicitly with social sustainability, presenting a structured analysis that highlights the need for strategic integration of digital technologies within organizational sustainability practices. It fills a gap in the literature by proposing a comprehensive framework for organizations to follow, thereby contributing to the theoretical and practical understanding of DT’s role in enhancing social sustainability.
Examining the efficacy of core competencies of municipal leaders in transforming local government in South Africa
Authors: Muringa Tigere , Shava Elvin 
Published: November 2024

PurposeThis study aims to examine the efficacy of municipal leaders’ leadership competencies in transforming local government in South Africa. Specifically, it focuses on identifying core competencies and obstacles that influence successful governance outcomes.Design/methodology/approachThe research employed a mixed-methods approach. Qualitative focus group interviews were conducted with n = 50 municipal leaders, stakeholders and experts. Additionally, an online survey was administered to N = 121 municipal leaders. The sample was drawn from eight local municipalities across South Africa, including Emfuleni Municipality, Ehlanzeni Municipality, Mbombela Municipality, Bushbuckridge Municipality, Msunduzi Municipality, Okahlamba Municipality, the City of Johannesburg and Tshwane MunicipalityNelson Mandela, Matlosana, Emfuleni, Ehlanzeni, Mbombela, Bushbuckridge, Msunduzi, Okahlamba, Mbombela Local Municipalities, the City of Johannesburg. Data analysis encompassed thematic coding and statistical analysis.FindingsThe findings suggest that the practical application of core competencies by municipal leaders is crucial for navigating complex challenges, fostering innovation and improving organizational culture and employee morale within local government agencies.Research limitations/implicationsResearch limitations include sample bias, reliance on self-reported data, contextual specificity to South Africa, potential for subjective interpretation and lack of long-term impact assessment.Practical implicationsUnderstanding the key competencies required for effective municipal leadership can inform training and development programmes for current and aspiring leaders. Practical application of these competencies can enhance governance outcomes, foster innovation and improve employee morale.Social implicationsEffective municipal leadership can contribute to social cohesion and service delivery, thus impacting the lives of citizens positively. By empowering employees and engaging stakeholders, municipal leaders can drive enduring outcomes and contribute to the overall well-being of communities.Originality/valueThis study fills a gap in existing research by examining the efficacy of leadership competencies within the context of South African municipal leadership. By identifying core competencies and obstacles, it provides valuable insights for improving governance and service delivery at the local government level.
Analysing brand attachment for restaurant table booking mobile application
Authors: Srivastava Neha , Malhotra Gunjan 
Published: November 2024

PurposeRestaurant table booking (RTB) mobile apps are transforming how consumers reserve tables in the restaurants of their choice. This study analyses how RTB mobile apps influence brand attachment (BA) and brand commitment (BC), highlighting the moderation effect of desire for uniqueness (DU) by integrating visual content theory and social exchange theory.Design/methodology/approachData [N = 414] were collected through the survey method from consumers having experience in using RTB mobile apps. The data were analysed through structural equation modelling using AMOS and SPSS PROCESS macro to examine moderated relationship.FindingsThe results confirm that content aesthetic quality, perceived technical interactivity and brand investments influence BA and BC in the RTB mobile app and also confirm the moderating role of the DU.Originality/valueThe present work is among the first to study the sources of BA in the RTB mobile app domain. Thus, it contributes to the literature on the restaurant industry to understand consumers' BA behaviour to achieve BC.
The public and private mix in the production of childcare: a case study of 21st century South Korea
Authors: Ryu Sunwoo 
Published: November 2024

Purpose The aim of this study is to demonstrate the usefulness of the “publicness” and “privateness” concepts in examining childcare policy reforms. Understanding them as having multiple facets, this paper challenges the way in which childcare-going-public is often simply assessed based on the coverage of publicly-funded childcare services. Instead, it highlights that the process should be more thoroughly examined by considering who pays for whom to provide childcare, where it takes place, how it is regulated, and what kinds of normative ideals it works towards.Design/methodology/approach The research design is two-fold. Firstly, it coins the concepts of “publicness” and “privateness” based on existing literature on welfare pluralism and public administration. It then unpacks the key facets constituting this conceptual twin within the childcare context, which are utilised to craft four models of childcare production. Secondly, this framework is analytically applied to explore 21st-century South Korea to track the changes and continuities in its childcare production models across four governments.Findings The analysis shows that while South Korea's childcare publicness increased in terms of funding, its privateness was bolstered in regard to the location of childcare, the way that publicly-funded childcare services were regulated and delivered, and the manner in which childcare was partially consolidated as a familial responsibility.Originality/value This paper proposes a new conceptual framework to analyse the complex and multi-layered process of how childcare goes public, which is analytically applied to a cross-governmental comparative study of South Korea.