bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why we should be sharing our operations: a game theoretic analysis of surgical learning
Authors: Soares AS , Chand M 
Published: February 2025

AbstractIntroductionSurgical training has traditionally relied on the master-apprentice model, emphasizing supervised repetition and immediate feedback within the operating room. With the advent of minimally invasive surgical techniques, the capability to record and digitally store surgical procedures has introduced new opportunities for detailed analysis and enhanced feedback mechanisms. Despite this potential, there is a lack of comprehensive systems to analyse recorded surgical procedures at scale.MethodsIn this study, we propose a cooperative game-theoretic model to examine the dynamics of surgical training, specifically focusing on the interactions between a master surgeon and an apprentice. The model incorporates both internal knowledge growth—stemming from direct collaboration—and external knowledge growth from supplementary educational resources. A characteristic function is proposed to quantify the utility (knowledge) generated by different coalitions of participants.ResultsOur findings demonstrate that collaboration between the master and apprentice leads to a synergistic increase in total knowledge value, surpassing the sum of their individual contributions. The integration of external resources significantly amplifies this effect, showing an exponential impact on knowledge acquisition over time. Proficiency analysis indicates that combining practical experience with structured external learning resources not only accelerates the apprentice’s progression to proficiency but also enhances the overall knowledge within the surgical community.ConclusionThe study underscores the potential of applying game-theoretic principles to optimize surgical education. By quantifying the influence of mentor-ship quality and external learning resources, we highlight actionable strategies to enhance surgical training outcomes. Embracing a combination of hands-on practice and external resources accelerates individual skill development and enriches the collective knowledge base. We anticipate that this conceptual framework will inform future educational models and encourage the adoption of collaborative and technology-enhanced learning practices in surgery.
Phasic and tonic pain serve distinct functions during adaptive behaviour
Authors: Tong Shuangyi , Denison Timothy , Hewitt Danielle , Lee Sang Wan , Seymour Ben 
Published: February 2025

ABSTRACTPain drives self-protective behaviour, and evolutionary theories suggest it acts over different timescales to serve distinct functions. Whilst phasic pain provides a teaching signal to drive avoidance of new injury, tonic pain is argued to support recuperative behaviour, for instance by reducing motivational vigour. We test this hypothesis in an immersive virtual reality EEG foraging task where subjects harvested fruit in a forest: some fruit elicited brief phasic pain to the grasping hand, and this reduced choice probability. Simultaneously, tonic pressure pain to the contralateral upper arm was associated with reduced action velocities. This could be explained by a free-operant computational framework that formalises and quantifies the function of tonic and phasic pain in terms of motivational vigour and decision value, and model parameters correlated with EEG responses. Overall, the results show how tonic and phasic pain subserve distinct objective motivational functions that support harm minimisation during ongoing adaptive behaviour.
Rēs ipSAE loquunt: What’s wrong with AlphaFold’sipTMscore and how to fix it
Authors: Dunbrack Roland L. 
Published: February 2025

AbstractAlphaFold’sipTMmetric is used to predict the accuracy of structural predictions of protein-protein interactions (PPIs) and the probability that two proteins interact. Many AF2/AF3 users have experienced the phenomenon that if they trim full-length sequence constructs (e.g. from UniProt) to the interacting domains (or domain+peptide), theiripTMscores go up, even though the structure prediction of the interaction is unchanged. The reason this happens is due to the mathematical formulation ofipTMin AF2/AF3, which scores the interactions of whole chains. If both chains in a PPI complex contain large amounts of disorder or accessory domains that do not form the primary domain-domain or domain/peptide interaction, theipTMscore can be lowered significantly. The score then does not accurately represent the accuracy of the structure prediction nor whether the two proteins actually interact. We have solved this problem by: 1) including only residue pairs in theipTMmetric that have good predicted aligned error (PAE) scores; 2) by adjusting thed0parameter (a function of the length of the query sequences) in the TM score equation to include only the number of residues with good interchainPAEs to the aligned residue; and 3) using thePAEvalue itself and not the probability distributions over the aligned error to calculate the pairwise residue-residuepTMvalues that go into theipTMcalculation. The first two are crucial in calculating highipTMs for domain-domain and domain-peptide interactions even in the presence of many hundreds of residues in disordered regions and/or accessory domains. The third allows us to require only the common output json files of AF2 and AF3 (including the server output) without having to change the AlphaFold code and without affecting the accuracy. We show in a benchmark that the new score, calledipSAE(interaction prediction Score from Aligned Errors), is able to separate true from false complexes more efficiently than AlphaFold2’sipTMscore. The resulting program is freely available athttps://github.com/dunbracklab/IPSAE.
Confirmatory insights intoELMOD3-associated autosomal dominant non-syndromic hearing loss
Authors: Yun Yejin , Park Minjae , Jeong Sohyang , Jung Sung Ho , Lee Sang-Yeon 
Published: February 2025

AbstractSensorineural hearing loss (SNHL) is one of the most common sensory disorders, predominantly driven by monogenic causes with a higher Mendelian contribution. AlthoughELMOD3variants have been implicated in both autosomal dominant (DFNA81) and autosomal recessive (DFNB88) hereditary deafness, only a single DFNA81 family has been reported, leaving the pathogenic role of the dominant allele largely unexplored. Through targeted panel sequencing, we herein identified a novel heterozygousELMOD3variant (c.640G>A; p.Gly214Ser) that co-segregates with autosomal dominant hearing loss in a Korean family. Molecular modeling and structure analysis indicates that replacing glycine at residue 214 with serine introduces spatial clashes with adjacent Ala160 and Cys162, thereby disrupting intermolecular interactions and compromising protein stability. Consistent with this, stability assays revealed a rapid degradation rate for the mutant protein.Furthermore, the ability to localize with F-actin in mutant protein was disrupted compared to the wild-type protein. Based on functional assays, the p.Gly214Ser variant demonstrated the functional pathogenicity and was classified as likely pathogenic according to the ACMG guideline for hearing loss. Collectively, these findings provide confirmatory insights intoELMOD3-associated DFNA81, potentially through a dominant-negative mechanism.
Population-specific Risk of Pharmacogenomics-related Inaccurate Drug Dosing of ICU Patients
Authors: Rostami Mahboubeh R. , Rodriguez-Flores Juan , Hssain Ali Ait , Al Shakaki Alya , Khan Huda , Vakayil Muneera , Karic Edin , Elhamid Maha , Al Tawil Lubna Gamal , Mezey Jason G. , Robay Amal , Crystal Ronald G. 
Published: February 2025

AbstractRationaleIntensive care units (ICU) patients are highly vulnerable to inaccurate drug dosing. Pharmacogenomics (PGx) characterizes the influence of inherited genetic variation on drug metabolism, playing an important role in the consequences of a given drug dose.ObjectivesTo assess the genetic-based risk of inaccurate drug dosing in the ICU.MethodsWe carried out whole genome sequencing (WGS) of 210 Qataris in ICU care at Hamad Medical Corporation (HMC), Doha, Qatar and assessed the WGS for predicted deleterious variants of genes that metabolize 30 drugs commonly prescribed in the ICU.Measurements and Main ResultsAnalysis of 210 Qatari ICU WGS identified 329 variants predicted deleterious associated with 85 genes known to affect metabolism of the 30 ICU drugs. Of the ICU patients that received the 5 most commonly prescribed drugs (warfarin, phenytoin, midazolam, vancomycin, levetiracetam), 93% had deleterious metabolism-related variants. Most (91%) patients carried at least one variant in a gene that that had the potential to affect the metabolism or activity of at least 1 drug that the patient received. Most patients had ≥14 deleterious variants of genes that affect the metabolism of administered drugs. Comparison of the deleterious variants related to metabolism of ICU drugs with African/African American and European populations revealed significant population specificity in ICU related PGx variants.ConclusionsTogether, these data suggest that population specific, pharmacogenomics based on the individual’s genome likely plays a significant role in effective, safe dosing in the ICU setting.
Intervention Mapping: A Multi-stage Investigation to Control Gastrointestinal Tract Infections at Primary Level
Authors: Mahmood Shahzad , Chaudary Nauman Ali , Farooq Raja Mohsin , Haider Hafiz Muhammad Ali , Tahir Umer Raza , Syed Komal 
Published: February 2025

AbstractInfectious diseases of the gastrointestinal (GI) tract are among the most common primary healthcare presentations, affecting 2.86 million people worldwide. These infections can include bacterial, viral, parasitic and fungal causes, and may present with nausea, diarrhea, abdominal pain, fever and dehydration. The objective of the study is to decrease disease burden through community transmission mitigation. Three selected key strategies illustrate how the mix-methods approach elaborated the quantitative analysis within the applied qualitative framing. Step 1: Research Phases Pre-Intervention: This research consists of three steps Pre-Intervention, Intervention, and Post-Intervention. In the first phase, disease prevalence is assessed and categorized by age, gender, and geography. The second phase implements a public health intervention tailored to disease risk factors and community needs. The final phase evaluates outcomes through data analysis.Findings highlight that targeted community health measures, such as health education, risk prevention, and intervention mapping, can significantly reduce GI infections, emphasizing the importance of evidence-based public health strategies.
3D phenotyping in a Colombian population reveals unique population and ontogenic facial patterns in genetic and rare disorders
Authors: Andreu-Montoriol Mireia , Pujol Marina , Echeverry-Quiceno Luis Miguel , Candelo Estephania , Heredia-Lidón Álvaro , Gómez Eidith , Solís Paula , Ramírez Diana , Ortiz Diana , Sevillano Xavier , Tayà Max Rubert , Esteban Maria Esther , Casado Aroa , Pachajoa Harry , Martínez-Abadías Neus 
Published: February 2025

ABSTRACTUp to 30-40% of genetic and rare disorders present with unique facial patterns. Clinical geneticists have traditionally assessed facial traits to suggest a first diagnosis and direct confirmatory genetic testing. However, to enhance the accuracy of early diagnosis using facial biomarkers, it is crucial to analyze the complexity of facial dysmorphologies using 3D technologies, further understand how facial ontogeny is altered within each condition, and broaden the analysis to include diverse human populations.In this study, we analyzed the 3D facial phenotypes associated to Down (DS), Morquio (MS), Noonan (NS), and Neurofibromatosis type 1 (NF1) syndromes, in an admixed Latin American population from Colombia, including 47 patients and 49 age matched controls. For each subject, we generated a three-dimensional facial model from 2D images captured by a multi-camera photogrammetric system, and recorded the 3D coordinates of 21 anatomical landmarks. Using geometric morphometrics, we characterized the 3D facial dysmorphologies associated with each syndrome and assessed the range of variation across syndromes as compared to controls. Finally, we tested whether these syndromes alter the ontogenetic trajectory of facial growth.Our results confirmed statistically significant facial shape differences associated with these genetic conditions, except for NF1. Consistent with our previous 2D analyses, we identified population-specific facial features in the Colombian patients that were not reported in individuals of European descent. Additionally, the pooled 3D analyses revealed a continuous spectrum of facial dysmorphology, with MS exhibiting the most severe dysmorphologies compared to controls. The ontogenic analyses further demonstrated that craniofacial development is altered in DS and MS, but not in RASopathies such as NS and NF1.Overall, our findings indicate that interpopulation and ontogenic differences in facial phenotypes should be considered to optimize and universalize the use of facial biomarkers. This approach could further help reduce the diagnostic odyssey associated with syndromic and rare conditions.
Projected ecological and disruptive impacts of climate change on malaria in Africa
Authors: Symons Tasmin L. , Moran Alexander , Balzarolo Ann , Vargas Camilo , Robertson Mairi , Lubinda Jailos , Saddler Adam , McPhail Michael , Harris Joseph , Rozier Jennifer , Browne Annie , Amratia Punam , Bertozzi-Villa Amelia , Bhatt Samir , Cameron Ewan , Golding Nick , Smith David L. , Noor Abdisalan M. , Rumisha Susan F. , Palmer Matthew D. , Weiss Daniel J. , Desai Naomi , Potere David , Sukitsch Nicholas , Woods Wendy , Gething Peter W. 
Published: February 2025

AbstractThe implications of climate change for malaria eradication in the 21stcentury remain poorly resolved. Many studies have focussed on parasite and vector ecology in isolation, neglecting the interactions between climate, malaria control, and the socioeconomic environment, including the disruptive impact of extreme weather. Here we integrate 25 years of data on climate, malaria burden, control interventions, socioeconomic factors, and extreme weather events in Africa. Using a geotemporal model linked to an ensemble of climate projections under the Shared Socioeconomic Pathway 2-4.5 (SSP 2-4.5) scenario, we estimate the future impact of climate change on malaria burden in Africa, accounting for both ecological and disruptive effects. Our findings suggest climate change could lead to 123 million (projection range 49.5 million - 203 million) additional malaria cases and 532,000 (195,000 - 912,000) additional deaths in Africa between 2024 and 2050 under current control levels. Contrary to the prevailing focus on ecological mechanisms, extreme weather events emerge as the primary driver of increased risk, accounting for 79% (50-94%) of additional cases and 93% (70%-100%) of additional deaths. Most increases are due to intensification in existing endemic areas rather than range expansion, with significant regional variation in impact. These results highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress toward malaria eradication in Africa.
TinA enables kinesin-14/KlpA to exhibit processive minus-end-directed motility
Authors: Visootsat Akasit , Popchock Andrew R. , Gao Yuan , Qiu Weihong 
Published: February 2025

ABSTRACTKinesin-14 motors contribute to spindle assembly by localizing to spindle poles and anchoring the minus ends of spindle microtubules. Unlike other kinesin-14 motors, KlpA uniquely exhibits plus-end-directed motility on single microtubules as individual homodimers. However, the mechanism by which KlpA achieves minus-end-directed motility on single microtubules remains elusive. Here, we report that TinA, a highly conserved microtubule-anchoring protein, serves as an activator of KlpA for minus-end-directed motility. TinA directly interacts with KlpA to form minus-end-directed complexes that exhibit continuous movement on microtubules with two distinct velocity modes. The assembly of KlpA-TinA complexes depends on TinA binding to the central stalk of KlpA. Furthermore, TinA is a microtubule-binding protein, with its C-terminal region playing a critical role in microtubule interaction. Deletion of the C-terminus of TinA markedly reduces its microtubule-binding ability and severely impairs the formation of KlpA-TinA complexes. Nonetheless, KlpA-TinA complexes formed without the C-terminus of TinA still exhibit minus-end-directed motility, albeit with a single velocity mode. Collectively, these findings provide critical mechanistic insights into how TinA modulates KlpA, enabling the kinesin-14 motor to achieve minus-end-directed motility.
Smoke exposure triggers rapid transcriptional changes and reveals glycosyltransferases linked to smoke taint in ripening grape berries
Authors: Paineau Manon , Liang Chen , Cochetel Noe , Shivani  , Figueroa-Balderas Rosa , Thilmony Roger , Rumbaugh Arran , Cantu Dario 
Published: February 2025

AbstractWith the increasing frequency of wildfires, vineyards are more often exposed to smoke, resulting in a higher risk of smoke taint in wine. This taint imparts undesirable “smoky” and “ashy” aromas and causes significant economic losses. Smoke-derived volatile phenols (VPs) in grape berries, metabolized into stable, non-volatile glycoconjugates via glycosyltransferases (GTs), underlie smoke taint formation. Here, we present the dwarf grapevine cultivar Pixie as a model system for smoke taint research. We generated a phased, telomere-to-telomere diploid genome using HiFi long-read sequencing, along with an expression atlas spanning 30 replicated samples across various tissues and developmental stages. We also constructed a second telomere-to-telomere assembly for Pinot Noir to assessGTexpression during berry ripening in the field. Controlled smoke-exposure experiments profiledGTexpression and enabled transcriptome-wide analyses at multiple time points. We measured VPs in both smoke-exposed and control samples, revealing 12GT1genes significantly upregulated by smoke, namedVitis vinifera smoke-inducible UGTs(VviSIUGTs). Their expression peaked one day post-exposure and declined by day three, mirroring glycoside accumulation dynamics. Gene co-expression network analyses highlighted stress-responsive modules enriched in theseVviSIUGTs, while transcription factor binding site analyses pinpointed stress-related regulatory elements in their promoters. These findings provide new insights into the molecular basis of smoke taint and identify potential targets for breeding and biotechnological interventions aimed at developing grapevine cultivars with reduced susceptibility to smoke damage.
Commensal acidification of specific gut regions produces a protective priority effect against enteropathogenic bacterial infection
Authors: Yang Jane L. , Zhu Haolong , Sadh Puru , Aumiller Kevin , Guvener Zehra T. , Ludington William B. 
Published: February 2025

AbstractThe commensal microbiome has been shown to protect against newly introduced enteric pathogens in multiple host species, a phenomenon known as a priority effect. Multiple mechanisms can contribute to this protective priority effect, including antimicrobial compounds, nutrient competition, and pH changes. InDrosophila melanogaster,Lactiplantibacillus plantarumhas been shown to protect against enteric pathogens. However, the strains ofL. plantarumstudied were derived from laboratory flies or non-fly environments and have been found to be unstable colonizers of the fly gut that mainly reside on the food. To study the priority effect using a naturally occurring microbial relationship, we isolated a wild-fly derived strain ofL. plantarumthat stably colonizes the fly gut in conjunction with a common enteric pathogen,Serratia marcescens. Flies stably associated with theL. plantarumstrain were more resilient to oralSerratia marcescensinfection as seen by longer lifespan and lowerS. marcescensload in the gut. Throughin vitroexperiments, we found thatL. plantaruminhibitsS. marcescensgrowth due to acidification. We used gut imaging with pH-indicator dyes to show thatL. plantarumreduces the gut pH to levels that restrictS. marcescensgrowthin vivo. In flies colonized withL. plantarumprior toS. marcescensinfection,L. plantarumandS. marcescensare spatially segregated in the gut andS. marcescensis less abundant whereL. plantarumheavily colonizes, indicating that acidification of specific gut regions is a mechanism of a protective priority effect.
A connection betweenVibrio choleraemotility and inter-animal transmission
Authors: Campbell Ian W. , Dehinwal Ruchika , Morano Alexander A. , Dailey Katherine G. , Zingl Franz G. , Waldor Matthew K. 
Published: February 2025

AbstractOutbreaks of cholera are caused by the highly transmissive pathogenVibrio cholerae. Here, a transposon screen revealed that inactivation of theV. choleraemotility-linked genemotVincreases infant mouse intestinal colonization. Compared to wild-typeV. cholerae, a ΔmotVmutant, which exhibits heightened motility in the form of constitutive straight swimming, localizes to the crypts earlier in infection and over a larger area of the small intestine. Aberrant localization of the mutant was associated with an increased number ofV. choleraeinitiating infection, and elevated pathogen burden, diarrhea, and lethality. Moreover, the deletion ofmotVcausesV. choleraeto transmit from infected suckling mice to naïve littermates more efficiently. Even in the absence of cholera toxin, the ΔmotVmutant continues to transmit between animals, although less than in the presence of toxin, indicating that phenotypes other than cholera toxin-driven diarrhea contribute to transmission. Collectively, this work provides experimental evidence linking intra-animal bottlenecks, colonization, and disease to inter-animal transmission.
Discovering new amyloid-like peptides using all-atom simulations and artificial intelligence
Authors: Kuang Xiaohan , Jalali Sharareh , Rahman Tasnima , Michalowski Jadhy , Sheng-Wong Caren , Wong-Ekkabut Jirasak , Su Zhaoqian , Dias Cristiano L. 
Published: February 2025

AbstractEstablishing the fundamental relationships between peptide sequences and fibril formation is critical both for understanding protein misfolding processes and for guiding biomaterial design. Here, we combine all-atom molecular dynamics (MD) simulations with artificial intelligence (AI) to investigate how subtle variations in the arrangement of a short peptide sequence affect its propensity to form fibrils. Our results show that small shifts in the distribution of hydrophobic residues and charge clusters can significantly influence both the nucleation rate and the stability of cross-βstructures. To rapidly extend this analysis over a wide sequence space, we developed an active learning–enhanced framework—Machine Learning for Molecular Dynamics (ML4MD)—that iteratively refines its predictions based on MD-derived aggregation data. ML4MD efficiently screens numerous peptide permutations and guides the discovery of previously unrecognized fibril-prone sequences, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.939. Overall, ML4MD streamlines the rational design of amyloid-like peptides by integrating detailed atomistic simulations with rapid and high-accuracy ML predictions.