bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bHLH transcription factor gene EGL3 accounts for the natural diversity in Arabidopsis fruit trichome pattern and morphology
Authors: Méndez-Vigo Belén , Arteaga Noelia , Murillo-Sánchez Alba , Alba Sonia , Alonso-Blanco Carlos 
Published: December 2024

Abstract
The number and distribution of trichomes, i.e. the trichome pattern, in different plant organs show a conspicuous inter- and intraspecific diversity across Angiosperms that is presumably involved in adaptation to numerous environmental factors. The genetic and molecular mechanisms accounting for the evolution of trichome patterns have just begun to be elucidated. In this study, we aimed to identify and characterize MALAMBRUNO 1 (MAU1), a locus affecting trichome number in the fruits of Arabidopsis (Arabidopsis thaliana) natural populations. To this end, we developed introgression lines (ILs) from the hairy fruit accession Doñana (Don-0) in the genetic background of the Ler strain with glabrous fruits. Genetic analyses of ILs showed that MAU1 affects fruit trichome patterns through synergistic epistasis with the MYB genes TRICHOMELESS1 (TCL1), GLABRA1 (GL1), and TRIPTYCHON (TRY). In addition, fine mapping and characterization of transgenic lines demonstrated that MAU1 is the bHLH transcription factor gene EGL3, for which Don-0 carries a gain-of-function semidominant allele. Gene expression analyses did not detect differences between EGL3 alleles, thus supporting that a structural missense mutation is the causal nucleotide polymorphism of Don-0. Further phylogenetic analyses of EGL3 showed that most Arabidopsis populations with hairy fruits belong to 3 haplogroups, suggesting that additional EGL3 natural alleles account for fruit trichome development. Finally, the characterization of EGL3 pleiotropy indicates that Don-0 hyperfunction also increases stem trichome branching. We conclude that EGL3 interactions in the core gene regulatory network of trichome development explain the Arabidopsis natural diversity for fruit trichome pattern and morphology.
General SIR model for visible and hidden epidemic dynamics
Authors: Nesteruk Igor 
Published: December 2024

SummaryTo simulate hidden epidemic dynamics connected with asymptomatic and unregistered patients, a new general SIR model was proposed. For some cases, the analytical solutions of the set of 5 differential equations were found which allow simplifying the parameter identification procedure. Two waves of the pertussis epidemic in England in 2023 and 2024 were simulated with the assumption of zero hidden cases. The accumulated and daily numbers of cases and the duration of the second wave were predicted with rather high accuracy. If the trend will not change, the monthly figure of 9 new pertussis cases (as it was in January-February 2023) can be achieved only in May 2025. The proposed approach can be recommended both for simulations and predictions of different epidemics.
A Framework for Autonomous AI-Driven Drug Discovery
Authors: Selinger Douglas W. , Wall Timothy R. , Stylianou Eleni , Khalil Ehab M. , Gaetz Jedidiah , Levy Oren 
Published: December 2024

SummaryThe exponential increase in biomedical data offers unprecedented opportunities for drug discovery, yet overwhelms traditional data analysis methods, limiting the pace of new drug development. Here we introduce a framework for autonomous artificial intelligence (AI)-driven drug discovery that integrates knowledge graphs with large language models (LLMs). It is capable of planning and carrying out automated drug discovery programs at a massive scale while providing details of its research strategy, progress, and all supporting data. At the heart of this framework lies the focal graph - a novel construct that harnesses centrality algorithms to distill vast, noisy datasets into concise, transparent, data-driven hypotheses. We demonstrate that even small-scale applications of this highly scalable approach can yield novel, transparent insights relevant to multiple stages of the drug discovery process and present a prototype system which autonomously plans and executes a multi-step target discovery workflow.Graphical Abstract
Calprotectin as a sepsis diagnostic marker in critical care: a retrospective observational study
Authors: Lengquist Maria , Sundén-Cullberg Vera , Hyllner Sofie , Koozi Hazem , Larsson Anders , Mellhammar Lisa , Friberg Hans , Schiopu Alexandru , Frigyesi Attila 
Published: December 2024

AbstractBackgroundDiagnosing sepsis in critical care remains a challenge due to the lack of gold-standard diagnostics. Calprotectin (S100A8/A9) has been proposed as a diagnostic marker to identify sepsis in critically ill patients. This study evaluated the diagnostic performance of calprotectin and C-reactive protein (CRP) to distinguish between sepsis and non-sepsis on intensive care unit (ICU) admission.MethodsAdmission biobank blood samples from adult patients admitted to four ICUs (2015-2018) were used to analyse calprotectin and CRP. All adult patients were screened retrospectively for the sepsis-3 criteria at ICU admission. The diagnostic performance of calprotectin and CRP was evaluated using receiver operating characteristic (ROC) curves.ResultsWe included 4732 patients, of whom 44% had sepsis. Calprotectin levels were higher in sepsis (p<0.001). The area under the receiver operating curve (AUROC) to diagnose sepsis was 0.61 for calprotectin compared to 0.72 for CRP (p<0.001). Among microbiological subgroups of sepsis patients, fungal sepsis had the highest level of calprotectin.ConclusionsThe diagnostic performance of calprotectin in identifying sepsis patients at ICU admission was inferior to that of CRP.
Benefits of Statins as Adjunct Therapy in the Management of Tuberculosis in Patients at a Referral Site in Ghana
Authors: Buabeng Nana Kwaku Bugyei , Amponsah Obed Kwabena Offe , Ayisi-Boateng Nana Kwame , Atawuchugi Paul , Boateng Kyei Emmanuel , Mohammed Aliyu , Buabeng Kwame Ohene , Danquah Cynthia Amaning 
Published: December 2024

AbstractBackgroundRepurposing medications that have demonstrated efficacy experimentally for drug-resistant tuberculosis (TB), such as statins, provides an opportunity to sidestep the time span and financial resources required to produce new antimicrobials to surmount resistance. However, this has not been extensively explored particularly in sub-Saharan Africa. This study investigated the benefits of statins as adjunct therapy in patients with TB, including those that are drug-resistant.MethodsThis was a case control study, involving the review of 3-year medical record of patients with tuberculosis on TB therapy with statins as adjunct (the cases), and those on TB therapy but not on statins at the Agogo Presbyterian Hospital in Ghana. The data obtained was analyzed using STATA version 17. Chi square test was used to determine the association between statin use as adjunct for TB therapy and improved outcomes (cure rate).ResultsStatin use in TB therapy as adjunct was associated with an increased incidence of TB cure (p<0.001). The relationship between statin and TB cure was still statistically significant, when age was adjusted for as a confounder in statin exposed individuals, (RR=4.9, p<0.05). Additionally, statins increased the cure rate of TB in the population studied, 6.61 per 100 population, 95% CI, (4.05-10.79) compared to 1.30 per 100 population 95 % CI, (0.65-2.59) in the absence of statins.ConclusionStatin use in patients on TB therapy was associated with increased cure. This study has affirmed that statins have potential benefits as an adjunct therapy in TB management.
The ketone body β-Hydroxybutyrate mediated epigenetic chromatin β-hydroxybutyrylation protects kidneys
Authors: Mandal Juthika , Aryal Sachin , Manandhar Ishan , Chakraborty Saroj , Mei Xue , Yeoh Beng San , Mell Blair , Kleinhenz Andrew , Tummala Ramakumar , Yang Tao , Saha Piu , Gunning William T , Vijay-Kumar Matam , Basrur Venkatesha , de la Serna Ivana , Joe Bina 
Published: December 2024

SummaryStarvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly β-hydroxybutyrate. β-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of β-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone β-hydroxybutyrylation, thereby influencing the transcriptome. Focusing on the kidney, which is an end organ protected by β-hydroxybutyrate, we examined histone β-hydroxybutyrylation-mediated chromatin remodeling. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. Significant β-hydroxybutyrylation was observed in the kidneys and the most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 (Hmgcs2), a gene responsible for the biosynthesis of β-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures were enriched with genes related to immune function such as protein tyrosine phosphatase receptor type C (Ptprc) and lymphocyte cytosolic protein 1 (Lcp1), which exhibited reduced transcription and translation. These results reveal that renal epigenetic histone β-hydroxybutyrylation, which concurrently modulates both energy metabolism and immune function is a mechanism underlying the dynamic health effects of β-hydroxybutyrate to protect kidneys and lower hypertension.
Flashzoi: An enhanced Borzoi model for accelerated genomic analysis
Authors: Hingerl Johannes C. , Karollus Alexander , Gagneur Julien 
Published: December 2024

AbstractAccurately predicting how DNA sequence drives gene regulation and how genetic variants alter gene expression is a central challenge in genomics. Borzoi, which models over ten thousand genomic assays including RNA-seq coverage from over half a megabase of sequence context alone promises to become an important foundation model in regulatory genomics, both for massively annotating variants and for further model development. However, its reliance on handcrafted, relative positional encodings within the transformer architecture limits its computational efficiency. Here we present Flashzoi, an enhanced Borzoi model that leverages rotary positional encodings and FlashAttention-2. This achieves over 3-fold faster training and inference and up to 2.4-fold reduced memory usage, while maintaining or improving accuracy in modeling various genomic assays including RNA-seq coverage, predicting variant effects, and enhancer-promoter linking. Flashzoi’s improved efficiency facilitates large-scale genomic analyses and opens avenues for exploring more complex regulatory mechanisms and modeling.
Variation of tooth traits in ecologically specialized and sympatric morphs
Authors: Jónsdóttir Guðbjörg Ósk , Ingimarsson Finnur , Snorrason Sigurður Sveinn , Steele Sarah Elizabeth , Pálsson Arnar 
Published: December 2024

AbstractDifferences in dentition between species relate to feeding specialisations, as examples of tetrapod dentition variation show clearly. The association of tooth traits and specialisations in non-mammalian vertebrates is less studied. We examined variation in dental traits in four sympatric morphs of Arctic charr (Salvelinus alpinus) which differ in feeding specialisations, head and jaw bone morphology. We studied tooth numbers in six bones (dentary, maxilla, premaxilla, palatine, vomer and glossohyal) and tooth angles in one bone (maxilla). We found fluctuating asymmetry in tooth numbers and angles and that the allometry of tooth numbers varied by bone but not morphs. The tooth numbers differed by morphs in four bones (dentary, palatine, vomer and glossohyal). In general, the morphs defined as pelagic had more teeth, and this relates partially to changes in bone shape. There was a difference in maxilla tooth angle, with benthic morphs having teeth which were angled more inwards. Dentary and maxilla tooth number correlated moderately with bone shape, maxilla tooth angle and premaxilla tooth number did not. While it is currently unknown what tooth characteristics are ancestral vs derived in these populations, the marked differences in specific bones presents an opportunity to explore rapid adaptive evolution in dentition.Statement and DeclarationThe authors declare that they have no conflict of interest
Pedigree Painter (PePa): a tool for the visualization of genetic inheritance in chromosomal context
Authors: Pozzi Andrea 
Published: December 2024

AbstractBackgroundData visualization is increasingly important in genomics, enabling researchers to uncover inheritance and recombination patterns across generations. While most existing tools focus on ancestry prediction, they lack functionality for analyzing known ancestries in controlled settings, such as determining parental contributions to offspring genomes. To address this gap, I developedpepa, a lightweight, modular tool that visualizes and quantifies genomic inheritance, designed for beginner and advanced users.Resultspepais a program for processing VCF files, assigning ancestries to SNPs, and clustering them into biologically meaningful regions. It generates human-readable comparison tables and visualizes inheritance patterns with chromosome paintings through R. Tested on fission yeast,peparevealed non-uniform recombination patterns, with chromosomes largely inherited from one parent and seemingly random recombination. Quantitative analyses showed differences in parental contributions at the nucleotide and gene levels, with some offspring inheriting similar percentages from parents. However, the painted chromosomes revealed that even offspring with similar percentages from one parent rarely inherit the same genomic region, highlighting the importance of this tool in drawing biologically meaningful insights.Conclusionpepaprovides an accessible and powerful solution for analyzing genomic inheritance, bridging experimental and computational biology. Its modular design and minimal dependencies allow adaptation to diverse organisms, facilitating intuitive visualization and quantitative insights into recombination dynamics.
The B-type cyclin Clb4 prevents meiosis I sister centromere separation in budding yeast
Authors: Lumbroso Gal , Cairo Gisela , Lacefield Soni , Murray Andrew W. 
Published: December 2024

AbstractIn meiosis, one round of DNA replication followed by two rounds of chromosome segregation halves the ploidy of the original cell. Accurate chromosome segregation in meiosis I depends on recombination between homologous chromosomes. Sister centromeres attach to the same spindle pole in this division and only segregate in meiosis II. We used budding yeast to select for mutations that produced viable spores in the absence of recombination. The most frequent mutations inactivatedCLB4, which encodes one of four B-type cyclins. In two wild yeast isolates, Y55 and SK1, but not the W303 laboratory strain, deletingCLB4causes premature sister centromere separation and segregation in meiosis I and frequent termination of meiosis after a single division, demonstrating a novel role for Clb4 in meiotic chromosome dynamics and meiotic progression. This role depends on the genetic background since meiosis in W303 is largely independent ofCLB4.
Fossil Freshwater Fishes from the Pliocene of northern Colombia and the Palaeogeography of northern South America
Authors: Ballen Gustavo A. , Montes Camilo , Carrillo-Briceño Jorge D. , Bogan Sergio , Reinales Sandra , de Pinna Mario C. C. , Jaramillo Carlos 
Published: December 2024

1AbstractFreshwater fishes from northern Colombia are reported from the Sincelejo and Ware formations, of Pliocene age. A total of ten taxa have been identified comprising two orders, five families, and nine genera. Characters from dental morphology, fin spines, and cranial bones are provided as taxonomic tools for the study of fossil fishes. All of the taxa are members of groups currently restricted to drainages east of the Andes, suggesting that physical drainage connection was still present by the Pliocene between the Amazon-Orinoco and trans-Andean drainages such as the Magdalena-Cauca, or that these groups persisted in the trans-Andean region at least until Pliocene times. The generaHemidoras,Serrasalmus, andTrachely-opterichthysare new records for the fossil fish fauna of South America. The genusZungarorepresents a new record for the trans-Andean region, whereas the genusPlatysilurusis for the first time in Colombia. Most of these occurrences also represent the youngest occurrences in the fossil record. Literature records are reidentified asPygocentrusfrom the La Venta fauna and the earily Oligocene in Peru. These assemblages suggest that the Sincelejo and Ware formations were deposited in rivers of large size that were part of a large drainage network connected to the Amazon-Orinoco despite being currently located west of the Andes. These findings suggest that the Cordillera Oriental and the Merida Andes were not dividing yet the drainage network in northern South America by the middle to late Miocene.
A qualitative study exploring how secondary school PE uniform policies influence body image, and PE engagement among adolescent girls
Authors: Porter Alice , Cawley Elin , Chapman Laura , Crisp Charlotte , Wadman Ruth , Barber Sally , Penton-Voak Ian , Attwood Angela , Jago Russell , Bould Helen 
Published: December 2024

ABSTRACTBackgroundMany adolescent girls experience body dissatisfaction and have low levels of physical activity. Secondary school Physical Education (PE) offers opportunities for girls to build self-confidence and stay active; however, PE uniforms can be a barrier to participation.ObjectivesTo explore how secondary school PE uniform policies influence body image and PE engagement (participation and enjoyment) among adolescent girls, and how these policies could be co-developed in future.DesignA qualitative study involving focus groups and interviews.Participants and settingForty-four 13-14-year-old girls and six PE staff members from six mixed-sex secondary schools in England.Data collection and analysisUsing topic guides and participatory activities to aid discussions, we explored PE uniform preferences and the influence on body image and PE engagement with adolescent girls, as well as the PE uniform policy development process with PE staff. Data were analysed using reflexive thematic analysis, supported by NVivo 14.ResultsThree themes were generated. Theme 1, ‘Striking the right balance between choice, comfort and uniformity’, describes the challenges of developing PE uniform policies that offer pupils choice to maximise comfort, whilst maintaining uniformity to ensure smartness, and to reduce social comparison. Theme 2, ‘PE uniforms are “made for boys”’ reflects that current policies can often provide unisex uniforms that don’t fit the female body, or gendered options that limit girls’ choices over style and fit. Theme 3, ‘Self-confidence influences comfort in wearing PE uniform, and in turn PE engagement’ suggests girls with high self-confidence may be less concerned about others’ opinions and how they look, leading to greater PE enjoyment, whereas girls with lower self-confidence described feeling self-conscious, especially in communal changing rooms, which could impact their comfort and PE engagement.ConclusionsOur findings suggest that developing PE uniform policies, which allow pupils to choose their own bottoms, wear additional layers, and wear PE uniform all day may improve comfort and inclusivity among girls, facilitating better PE engagement.Strengths and limitations of this studyOur qualitative approach, using participatory activities to prompt discussions, enabled in-depth exploration into how PE uniforms can influence body image and PE engagement among adolescent girls.Data from adolescent girls and PE staff were triangulated to ensure PE uniform policy recommendations considered both pupil and staff perspectives.Due to challenges with recruiting schools, our sample was made up of mixed-sex, mainly affluent schools in South West England only.We had limited representation from pupils of ethnic minority backgrounds and those with low levels of PE enjoyment.
Association of fibrinogen αE, fibrinogen γ′, and sialylated fibrinogen with development of ischemic stroke in patients with recently diagnosed type 2 diabetes
Authors: Daugaard Nicoline , Bladbjerg Else-Marie , Svane Helene Matilde Lundsgaard , Thomsen Reimar Wernich , Nielsen Jens Steen , Palarasah Yaseelan , de Maat Moniek P.M. , Münster Anna-Marie Bloch 
Published: December 2024

AbstractBackgroundStroke is a major cause of death globally, especially in type 2 diabetes (T2D) patients. Fibrinogen is known to predict stroke risk, but fibrinogen is a highly variable protein and we hypothesized that fibrinogen variants can improve stroke prediction.ObjectivesTo investigate the association of total fibrinogen and fibrinogen variants with risk of ischemic stroke in T2D patients.MethodsIn a nested case-control study with a median follow-up of 4.1 years, we included 144 T2D patients with ischemic stroke (cases) and 144 matched T2D patients without ischemic stroke (controls). We measured total fibrinogen, absolute and relative (ratio between variant and total fibrinogen) levels of three fibrinogen variants (fibrinogen αE, fibrinogen γ′, and sialylated fibrinogen) and compared levels between cases and controls. We used logistic regression to determine the association with stroke risk.ResultsTotal fibrinogen and absolute levels of fibrinogen αE, fibrinogen γ′, and sialylated fibrinogen were higher in stroke cases than controls (total fibrinogen 3.55 and 3.44 g/l; fibrinogen αE: 8.95 and 8.55 µg/ml; fibrinogen γ′: 638 and 626 µg/ml; sialylated fibrinogen: 1.32 and 1.18 arbitrary units). Absolute levels of fibrinogen positively associated with risk of stroke, both for total fibrinogen (highest vs lowest tertile; adjusted odds ratio (OR) 1.9 (95% CI 0.9-4.2)), fibrinogen γ′ (OR 1.8 (0.8-3.8)), and sialylated fibrinogen (OR 2.5 (1.1-5.8)). Relative levels of fibrinogen variants did not convincingly associate with stroke risk.ConclusionPatients with T2D who developed stroke had increased levels of total fibrinogen, fibrinogen αE, fibrinogen γ′, and sialylated fibrinogen compared with T2D controls. Total fibrinogen and absolute, but not relative, levels of fibrinogen γ′ and sialylated fibrinogen prospectively associated with a 2-fold increased risk of ischemic stroke.