Biology subjects

Clark, A.

Publications and source records attributed to Clark, A..

At least 19 recordsLinked to original sources

bioRxiv2026

The anterior insular cortex mediates higher-order threat learning and memory

Learning about potential threats is indispensable for survival, and its deficits underlie numerous neuropsychiatric disorders. Human brain imaging suggests the anterior insular cortex (AIC) as a key neural correlate of threat learning, yet its mechanistic role remains unclear. Leveraging multimodal systems neuroscience approaches, we demonstrate that AIC excitatory neurons, specifically layer 5 pyramidal neurons projecting to the basolateral amygdala, are essential for higher-order threat learning/memory. They are specifically required when a predictor is temporally separated from an aversive event or when the predictive information is embedded within a diffuse context. In contrast, the AIC is dispensable for elementary, temporally contiguous threat learning. Surprisingly, while the AIC promotes memory formation, it also constrains the level of fear expression during retrieval in a context-dependent manner. This bidirectional control is mediated by the recruitment of distinct AIC neuronal ensembles. Together, we identify a novel circuit mechanism for bidirectional regulation of higher-order threat learning/memory.

neuroscience↗

bioRxiv2026

Compression through internal and external information bottlenecks resolves information intractability across brains, bodies and worlds

Agents are constantly challenged to navigate uncertainty in a world that contains far more information that they can process, improving predictability by exploiting regularities from the environment. This frames the challenge of reducing information intractability as the main problem any artificial or biological agent needs to solve. We argue that this challenge is solved through the systematic use of information bottlenecks--a diverse suite of strategies functioning to compress and selectively filter environmental information so as to build tractable representations of the world. We show that such bottlenecks are adaptive and operate across multiple scales, from the evolution of neural circuits and sensory systems to the actions that organisms use in real-time to select and structure their own sensory inputs. A key aspect of our proposal is that information bottlenecks are not only internal and biological, but can also be externalized through actions in the world. By transforming their environments, agents construct external bottlenecks--material and cultural mechanisms that reduce the cost of inference and transmit regularities that are shared across individuals and even across generations. From this perspective, niche construction, material culture and even social and cultural norms, can be also understood as adaptive informational mechanisms, collective information bottlenecks that alter our worlds in ways that promote predictive success. Agents increasingly solve the intractability problem not only through evolutionary changes in their biology and internal neural mechanisms, but by systematically constructing and exploiting information bottlenecks in the world. Culture itself, we suggest, is just such a bottleneck-constructing mechanism.

neuroscience↗

bioRxiv2026

A streamlined proof of concept CRISPR-based environmental biosurveillance platform for the detection of closely related invasive rats

Environmental biosurveillance requires technologies that can rapidly translate genomic information into sensitive, specific, and deployable detection tools. Here, we present the first proof-of-concept application of SENTINEL (Smart Environmental Nucleic-acid Tracking using Inference from Neural-networks for Early-warning Localization), integrating artificial-intelligence-guided target discovery, isothermal amplification, CRISPR-based detection, and environmental DNA. Using Rattus exulans, R. norvegicus, and R. rattus as a challenging model of closely related invasive vertebrates, SENTINEL achieved species-specific discrimination without detectable cross-reactivity and sensitivities of 10 aM for plasmid DNA and 10 fg/uL for genomic DNA. Selected assays also showed reproducible semi-quantitative performance and successful eDNA validation. This first application of CRISPR-based environmental biosurveillance to terrestrial invasive vertebrates demonstrates a transferable framework for converting sequence data into field-deployable assays, with potential applications across biosecurity, conservation, agriculture, and environmental monitoring.

ecology↗

bioRxiv2026

Microbiome-mediated Biotransformation of Human Lactoferrin (effera(R)) Enhances Epithelial Barrier Function in an Ex Vivo Adult Model

Lactoferrin is a multifunctional iron-binding glycoprotein that supports intestinal barrier function, immune regulation, and a favorable gut microbial environment. However, the contribution of gut microbial biotransformation to its gastrointestinal activity remains poorly understood. We investigated whether effera(R), a precision fermentation-derived recombinant human lactoferrin, supports intestinal barrier function through microbiome-mediated mechanisms. effera(R) underwent simulated upper gastrointestinal digestion followed by ex vivo colonic fermentation using the validated SIFR(R) technology pipeline, which employs bioreactors that are inoculated with fecal microbiota from six healthy adult donors. Microbial activity was evaluated by measuring short-chain fatty acid (SCFA) production, bacterial cell density, and microbiome composition. effera(R) produced dose-dependent increases in the production of SCFAs and bacterial cell density demonstrating enhanced microbial metabolic activity. These metabolic changes were accompanied by shifts in key microbial groups within Bacillota_A and Bacteroidota. Intact effera(R) and cell-free post-colonic fermentation-derived products were evaluated in a Caco-2/THP-1 epithelial-immune co-culture model under basal and lipopolysaccharide-challenged conditions. Whereas intact protein did not significantly improve epithelial barrier integrity, effera(R)s post-colonic fermentation-derived products significantly enhanced transepithelial electrical resistance (TEER) under basal conditions and produced an even stronger barrier-protective response following LPS challenge. Across matched doses, effera(R) consistently generated greater TEER responses than bovine lactoferrin. Improved barrier function was accompanied by increased expression of tight-junction-associated targets ZO-1 and occludin and reduced secretion of CXCL-10 and IL-8. Together, these findings demonstrate that microbial biotransformation enhances the biological activity of effera(R), linking increased microbial metabolism with improved epithelial barrier integrity and modulation of inflammatory signaling. This integrated study provides a strong mechanistic foundation for the use of human lactoferrin in adult gut-health applications and offers valuable guidance for future adult clinical studies and infant-relevant investigations.

microbiology↗

bioRxiv2026

Expanded implementation of Fast & Fair paid peer review reduces time to first decision without reducing review quality in a biology journal

Traditional peer review is often slowed by delays in identifying willing reviewers and waiting for completed review reports. In a 2024 pilot on the journal Biology Open, we showed that Fast & Fair peer review, which uses pre-contracted paid reviewers and a structured editorial timeline, could deliver rapid, high-quality peer. Here, we report the expanded implementation of Fast & Fair at Biology Open in 2025. From 1 April 2025 onward, all direct submissions to the journal were considered for Fast & Fair peer review unless appropriate pre-contracted reviewer expertise was unavailable. Reviewers were paid 220 GBP per manuscript only if they completed the review on time, and the review met editorial quality expectations. Among peer-reviewed manuscripts submitted in 2025, Fast & Fair reduced time to first decision with reviews from a mean of 37.7 working days under conventional peer review to 5.5 working days. Reviewer commitment also improved. Fast & Fair invitations were accepted more often than conventional invitations (67% versus 23%), had lower nonresponse (13% versus 39%), and had higher completion among accepted invitations (98% versus 87%). Faster review was not associated with reduced review quality. Handling editors scored each review for usefulness in editorial decision-making. Fast & Fair produced fewer low-scoring reports than conventional peer review. Editorial behavior was also unchanged, with similar first-decision profiles and final acceptance rates (59% versus 61%). While financial sustainability remains to be tested at scale, the Fast & Fair model addresses a major bottleneck in traditional peer review by replacing ad hoc reviewer recruitment with conditional compensation, predefined quality standards and a strict editorial timeline.

scientific communication and education↗

bioRxiv2026

3D cortical microtissue with innate microglia for studying real-time cell behavior across maturation and inflammatory response

Microglia represent the immune component of the central nervous system (CNS) that displays dynamic responses to injury and disease. Across the developing and mature CNS, microglia emerge as immunocompetent cells that continuously survey their surroundings to maintain tissue homeostasis and respond to threats. There remains a gap in 3D in vitro models that contain microglia and can provide both developmental and mature functional hallmarks. Using a 3D neural multicellular model, cortical microtissues, derived from primary rat cortical cells, we conducted live imaging to monitor microglia dynamics from early, middle, and late stage microtissue maturation. We optimized a within-micromold imaging approach that allows for live microglia imaging without removing microtissues from their culturing environment. We confirm that microglia exhibit baseline surveillance characterized by relatively stationary somas and highly dynamic cell processes that continuously extend and retract. Following proinflammatory challenges, microglia engulf lipopolysaccharide particles, accompanied by dynamic shifts in motility patterns; and rapidly respond to laser-induced tissue damage through process extension, whole-cell displacement, and local recruitment. Lastly, we show that microtissue age in culture strongly influences both baseline and directed motility profiles. Collectively, these studies demonstrate that within a 3D microenvironment, microglia exhibit pronounced changes in morphology, surveillance area, motility, and injury response across microtissue maturation. Microtissues can serve as a valuable in vitro platform for both microglia developmental studies and investigations of brain inflammation related to CNS injuries, infections, and diseases.

neuroscience↗

bioRxiv2026

A systematic review and meta-analysis of the effects of older age on skeletal muscle mitochondrial function, as measured by 31P magnetic resonance

ObjectiveLoss of skeletal muscle mass and performance is a hallmark of ageing. Mitochondrial function has been suggested as a critical determinant of skeletal muscle performance. However, mixed results have been reported regarding mitochondrial function in older individuals. Therefore, the primary objective of this systematic review is to determine whether 31P-MRS-derived {tau}PCr, reflecting mitochondrial oxidative capacity, is reduced in ageing skeletal muscle. MethodsA preregistered systematic literature review was performed using the databases MEDLINE, EMBASE, SPORTDiscus, and Cochrane Central Register of Controlled Trials (CENTRAL). Papers were included if they reported {tau}PCr as measured by 31P-MRS; and studied individuals over 65 years of age in combination with a younger control group. Differences between young and older groups were assessed using random effects meta-analysis. ResultsWe included 20 papers in total, of which 2 measured 2 muscles, 5 focused on the tibialis anterior (TA) muscle, 11 on the calf muscles, 5 on the quadriceps, and 1 on the flexor digitorum longus. No statistically-significant differences were found in {tau}PCr between older and younger adults for all muscles combined (Hedges g=0.11 (p=0.487). Inter-study heterogeneity was high ({tau}2=0.36, I2=72.49%, H2=3.64). Sub-analyses for the individual muscles showed longer {tau}PCr in the quadriceps (g=0.65, p<0.001) in older adults, but shorter {tau}PCr in the TA muscle (g=-0.64, p<0.001). For the calf muscles, no differences were detected between older and young individuals (g=0.20, p=0.377). ConclusionNo uniform age-related decline was found for {tau}PCr when comparing all studies together. Substantial heterogeneity was observed between the individual muscles, with {tau}PCr being prolonged in the upper leg muscles in older adults, but shortened in the tibialis anterior. This suggests more work using standardised settings and well-defined cohorts is needed.

physiology↗

bioRxiv2026

Engineered OAA lectins as selective and sensitive high mannose glycan targeting tools

The Oscillatoria agardhii agglutinin (OAA) lectin interacts with N-glycans through a pentamannose core shared among all high mannose N-glycans (HMGs). Because HMGs only differ by number of mannose sugars, there is a scarcity of tools sensitive enough to resolve each specific HMG structure in their biological context. Here, we investigate the sequence space of OAA to tune the binding properties towards selectivity of Man5GlcNAc2, thus generating a structure-specific detection tool. Using phage display to screen a diverse library of OAA variants, we identify a variant with high selectivity for Man5GlcNAc2 that we further dissect to reveal four mutations necessary for selectivity and two mutations responsible for enhanced affinity for all HMGs. Coupling a crystal structure of the selective variant with binding analysis of specific point mutations, we reveal how co-dependent mutations achieve selectivity. We then demonstrate how variants can be valency-modulated on a single beta-barrel scaffold to improve their binding properties by orders of magnitude. Finally, we showcase the applicability of engineered OAA variants as improved HMG profiling tools and tunable antiviral agents.

biophysics↗

bioRxiv2025

Metal-Triggered Rheological Switching in Engineered Lanmodulin Condensates

Reliable recovery of rare earth elements (REEs) is increasingly important for energy and communication technologies, yet current separation methods rely on harsh chemistries and are difficult to scale sustainably. Biological strategies offer a promising alternative but typically require immobilized proteins, introducing diffusion limitations and regeneration challenges. Here, we engineer a phase-separating variant of the high-affinity lanthanide-binding protein Lanmodulin (LanM) by fusing it to an encapsulation peptide (EP) microdomain. The resulting chimera, EP-LanM, undergoes liquid-liquid phase separation upon REE binding, forming condensates whose formation and dynamic properties are governed by metal stoichiometry and temperature. These condensates enable selective capture and release of La3 and Nd3 and support efficient recovery and reuse of the protein. Our findings show that metal-triggered protein condensation can be harnessed as an aqueous, reversible mechanism for REE enrichment, establishing a generalizable biophysical approach for designing functional phase-separating proteins for selective metal separation.

biophysics↗

bioRxiv2025

Measurement of nitric oxide production in mouse tracheal epithelial cell cultures differentiated at the air liquid interface.

Airway ciliary dysfunction often leads to impaired mucociliary clearance, a defect frequently associated with dysregulation of canonical nitric oxide (NO) signaling. Indeed, many airway diseases exhibit aberrant levels of exhaled NO, a feature commonly used as a diagnostic indicator in patients. While this measurement is routinely performed clinically, there is currently no validated approach to assess NO release from airway ciliated cells in vitro, limiting mechanistic studies of NO regulation and function. An established method to study airway diseases in vitro is the use of cultured mouse tracheal epithelial cells (MTECs) differentiated at the air-liquid interface (ALI). Here, using this model, we develop a protocol to measure NO released from ciliated cells and accumulated in apical mucus, collected from the ALI-differentiated cultures. Using established instrumentation for NO analysis and a triiodide-based assay, we quantify nitrite, a stable NO metabolite and biomarker of NO production. For assay validation, cells were treated with the NO donor Diethylenetriamine NONOate (DETA-NONOate or DETA/NO) or the NO synthase inhibitor N({omega})-Nitro-L-arginine methyl ester (L-NAME). Together, these approaches demonstrate that this method reliably detects NO in samples from ALI-differentiated airway epithelia, providing an accurate in vitro platform to quantify NO release and model diseases associated with abnormal NO metabolism. SUMMARYThe goal of this current protocol is to describe a cell culture-based method to study airway diseases associated with altered nitric oxide (NO) signaling. This method describes the quantification of NO in airway epithelia differentiated at the air-liquid interface (ALI) using a triiodide-based chemiluminescence assay.

molecular biology↗

bioRxiv2025

Pervasive context-dependent effects in the genetic architecture of complex and quantitative traits revealed by a powerful multiparent mapping population in yeast

The genetic dissection of complex traits remains a major challenge in basic and biomedical research, but is essential for understanding the molecular pathways that shape phenotypic variation and for developing predictive models of trait and disease susceptibility. Here, we leverage a novel multiparent mapping population of budding yeast, CYClones, comprising 9,344 haploid strains derived from eight genetically diverse founders, to identify quantitative trait loci (QTL) and systematically investigate the genetic architecture of growth rates across ten environmental conditions. In total, we identified 349 QTL (ranging from 19 to 49 QTL per growth condition) that explained between 61% and 100% of narrow sense heritability across traits. The high power and resolution of CYClones revealed that growth traits exhibited distinct, condition-specific genetic architectures with extensive allelic heterogeneity, where a QTL was the result of multiple tightly linked causal variants. We also observed pleiotropy among QTL with complex, trait-dependent allele effects that are also consistent with allelic heterogeneity. Genetic complexity varied widely, with some traits showing nearly Mendelian architectures, while others were highly polygenic. Introgressed loci played a prominent role in the landscape of growth rate QTL, including one that is localized to a 2.4 kb interval in the PCA1 cadmium transporter and explains 72% of variation in cadmium resistance and another large-effect QTL that alters growth on galactose via complex non-additive interactions with the transcriptional regulator GAL3. In both cadmium and galactose conditions, we show that allelic variation at a small number of loci stratifies the population into regulatory or physiological subgroups, each with distinct genetic architectures, a phenomenon we term allele-dependent stratification. Collectively, our results provide novel insights into the genetics of growth rates in budding yeast, the architectural features of genetic complexity, and demonstrate that CYClones is a powerful platform for revealing the molecular basis of complex trait variation.

genetics↗

bioRxiv2025

CYClones: A highly powered, fully genotyped, 8-parent yeast mapping population

The budding yeast Saccharomyces cerevisiae is a remarkably adaptable organism that thrives in diverse environments. Global sequencing of natural isolates has revealed extensive genetic diversity within the species. Here, we describe the construction and characterization of CYClones (Collaborative Yeast Cross clones), a library of 11,392 segregants generated from a multiparent funnel cross of eight genetically diverse parental strains. To enable the genetic dissection of complex traits, we imputed whole-genome sequences for all segregants and show that CYClones captures a substantial fraction of the global genetic diversity of S. cerevisiae. Haplotype representation is well maintained, with each parental haplotype present at >5% frequency across >95% of the genome. Simulations demonstrate that CYClones has [≥]95% power to detect variants with heritability as low as 0.36%, with mapping resolution often finer than the length of a single gene. In summary, CYClones is a powerful community resource for dissecting the genetic architecture of complex and quantitative traits, uncovering context-dependent mutational effects, and identifying causal variants underlying phenotypic diversity.

genetics↗

bioRxiv2025

Thinging Through Modelling. Active Inference Meets Material Engagement

In this simulation study, we adopt the comprehensive neurocomputational approach of Active Inference (AIF) to illustrate some key concepts of Material Engagement Theory (MET) [1]. MET posits that craftwork does not require, or rely on, rich internal pre-planning, i.e., complex and highly detailed representations that occur mainly in the makers head. Instead, the maker engages materiality through thinging, where the human agent (the maker) is guided by and leverages the materiality of the artefact (such as a spinning of clay or a chunk of marble). MET assigns a crucial co-participatory role to materiality, attributing agency to it. We investigate METs claims through the widely adopted theory of AIF [2]. Our first aim is to simulate the plausibility of the (creative) thinging, adopting a simple modelling scenario. Then, we also discuss its applicability to other, more complex cases, which seem to require greater levels of pre-thinking (e.g., planning, imagining and conceptualising outcomes). We highlight how these cases, too, align with the general principle of thinging. With our AIF neurocomputational understanding, we explain that even in these situations, the predictive brains involved in the creative process attempt to minimise the complexity of their internal model. The upshot of this is that, always and everywhere, our human minds engage the materiality to make the most of the characteristic dynamics of the world surrounding us - things and processes alike.

neuroscience↗

bioRxiv2025

Drivers of individual plant species contributions to β-diversity are scale-dependent

Species introductions and native extirpations are driving biotic homogenisation in plant communities by reducing {beta}-diversity. Individual species vary in their contributions to {beta}-diversity (Species Contribution to {beta}-Diversity; species-{beta}), yet our understanding of how species characteristics shape these contributions remains limited. Additionally, although the ecological processes influencing {beta}-diversity are known to vary with spatial scale, we lack understanding of how species contributions, or their underlying determinants, change across scales. Here, we modelled how plant functional traits, phylogenetic relatedness, and introduction status influence their contributions to {beta}-diversity using plant community data from 429 plots surveyed from 2017-2023 across three nested spatial scales (up to 1 km2) in nine sites spanning four countries. We extended the analysis to broader spatial extents (100 km2 to the entire UK) using GBIF occurrence data. We found that functional traits associated with competitive ability influenced species-{beta}, but the direction and strength of their effects varied with scale. Likewise, phylogenetic novelty increased species-{beta} at small scales but reduced it at larger ones. After accounting for traits and phylogeny, introduced species consistently contributed less to {beta}-diversity than native species--especially at broader spatial extents. These results demonstrate that species ecological and evolutionary characteristics shape their contributions to {beta}-diversity, but that these effects are scale-dependent. Our findings highlight the importance of scale-explicit approaches in understanding both the determinants of {beta}-diversity, and how we can combat its loss to mitigate biotic homogenisation.

ecology↗

bioRxiv2025

TFAP2A+ embryonic progenitor cells undergo fate diversification to give rise to human amnion, germline, and mesoderm

Amnion, germline and mesoderm specification at the posterior end of the human embryo occur around the same time in vivo. Similarly, in vitro generation of germline and amnion is associated with mesoderm induction regardless of differentiation platform. Yet, the lineage relationships between amnion, germline and mesoderm remains unresolved. By adding Basement Membrane Extract (BME) to the media, we demonstrate emergence of TFAP2A+/SOX2-epithelial progenitor cells which develop in response to BMP receptor signaling. We track the order of embryonic events that take place from this progenitor pool revealing that amnion-like cells (AMLCs) and primordial germ cell (PGC)-like cells (PGCLCs) are specified first. Shortly after, gastrulating mesoderm-like cells (MeLCs) arise that undergo an epithelial to mesenchymal transition (EMT). These results highlight the interconnected role of basement membrane deposition and BMP receptor signaling in the specification of human germline, amnion and mesoderm from TFAP2A+ embryonic progenitors.

developmental biology↗

bioRxiv2025

The Freshwater Sounds Archive

Freshwater ecosystems are full of underwater sounds produced by amphibians, aquatic arthropods, reptiles, plants, fishes, and methane bubbles escaping from the sediment. Although much headway has been made in recent years investigating the overall soundscapes of various freshwater ecosystems around the world, there remains a significant knowledge gap in our collective inability to accurately and reliably link recorded sounds with the species that produced them. Here, we present The Freshwater Sounds Archive, a new global initiative, which seeks to address this knowledge gap by collating species-specific freshwater sound recordings into a publicly available database. By means of metadata collection, we also present a snapshot of the species studied, the recording equipment, and recording parameters used by freshwater ecoacousticians globally. In total, 61 entries were submitted to the archive between the 4th of March 2023 and the 30th of April 2025, representing 16 countries and 6 continents. The most numerous taxonomic group was arthropods (29 entries), followed by fishes (14 entries), amphibians (10 entries), macrophytes (7 entries), and a freshwater mollusk (1 entry). The majority of the submissions were from European countries (27 entries), of which the United Kingdom was the most represented with 14 entries. The next most represented region was North America (11 entries), followed by South America (8 entries), Oceania and Asia (5 entries each), Africa (3 entries), and the Middle East and Central America with 1 entry each. The global south, polar regions, and areas with an elevation >500 m (asl) were underrepresented. The field of freshwater ecoacoustics to date has largely focused on the analysis of sound types due to a current lack of knowledge of species-specific sounds. The Freshwater Sounds Archive presents an opportunity to move beyond the sound type approach, and towards an approach with higher taxonomic resolution, ultimately resulting in species-specific descriptions. Furthermore, The Freshwater Sounds Archive will provide freshwater ecoacousticians with one of the main tools required to start creating annotated training datasets for machine learning models from soundscape recordings by referring to known species sounds present in the archive. In the long-term, this will result in the automatic detection and classification of species-specific freshwater sounds from soundscape recordings, such as indicator, invasive, and endangered species.

ecology↗

bioRxiv2025

The novel RNA polymerase I transcription inhibitor PMR-116 exploits a critical therapeutic vulnerability in a broad-spectrum of high MYC malignancies.

Ribosome biogenesis (RiBi) is a key determinant of cell growth and proliferation and is highly elevated in cancer due to the activation by oncogenes such as MYC. First-generation RiBi inhibitor CX-5461, while demonstrating clinical potential for cancer treatment, also induces DNA damage through off-target inhibition of TOP2 and potentially other mechanisms, bringing into question RiBi as a target for cancer therapy. In this study, we test second-generation RiBi inhibitor, PMR-116. PMR-116 exhibits improved drug-like properties compared to first-generation RiBi inhibitors and has robust anti-tumour activity in the absence of global DNA damage signalling in a broad range of pre-clinical models of haematologic and solid cancers, particularly in malignancies where MYC is either the driver of disease or is elevated. Thus, our work demonstrates that RiBi is a genuine target for cancer therapy and highlights the potential to exploit a critical therapeutic vulnerability in high-MYC human cancers with dismal therapeutic outcomes. Statement of significanceDespite the development of new cancer therapies, most advanced malignancies remain incurable. We demonstrate that PMR-116, a second-generation RiBi inhibitor, has robust therapeutic efficacy in preclinical models of cancer, offering great promise to treat a broad spectrum of human solid and haematologic malignancies, especially where MYC is a driver.

cancer biology↗

bioRxiv2025

Fast & Fair peer review: a pilot study demonstrating feasibility of rapid, high-quality peer review in a biology journal

Traditional peer review is slow, often delayed by the time-consuming process of identifying reviewers and lengthy review turnaround times. This study tests the feasibility of the Fast & Fair peer review initiative by evaluating whether we could implement and adhere to a structured timeline for rapid peer review at Biology Open. A 6-month pilot conducted from July to December 2024 evaluated a structured workflow with pre-contracted reviewers under two payment models: a freelance model or a retainer model. All manuscripts assigned to two of the journals ten academic editors were included in the Fast & Fair peer review initiative experiment. A structured editorial time-line ensured that all manuscripts received reviews and first decisions within 7 business days. The results demonstrated that 100% of Fast & Fair peer review initiative manuscripts met the turnaround target, with a mean of 4.6 business days (n=20 manuscripts). Review quality was maintained, as indicated by assessments by academic editors. The freelancer model outperformed retainers in cost-effectiveness. These findings suggest that the Fast & Fair peer review initiative is feasible and does not compromise review quality. While scalability remains to be tested, the initiative eliminates a major bottleneck in traditional peer review by streamlining reviewer identification and enforcing a strict editorial timeline.

scientific communication and education↗