bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of LEEP in Treating CIN 2–3 During Pregnancy
Authors: Siegler Yoav , Bornstein Jacob , Lavie Ofer , Vaknin Zvi , Kugelman Nir ,   Israeli Society of Colposcopy and Cervical Pathology, Siegler Efraim 
Published: February 2025

Abstract
Cervical intraepithelial neoplasia (CIN) 2–3, a premalignant lesion usually treated by Loop Electrosurgical Excision Procedure (LEEP) in nonpregnant women, is addressed differently in pregnant women.
Data from 2006 to 2023 on 178 pregnant women with CIN 2–3 were provided by the Israeli Society of Colposcopy. Sixty-seven underwent LEEP within 15 weeks of gestation with only minor complications. Of the 57 continuing pregnancies, 53 (93%) delivered at term, 2 (3.5%) at 34–37 weeks, and 2 (3.5%) experienced missed abortions. One hundred eleven women were followed through pregnancy without LEEP. Of that group, 5 women were lost to follow-up. From 173 women on whom we have follow-up data, 9 (5.2%) were finally diagnosed with cervical cancer, 132 women (76.3%) remained CIN 2–3, and 32 women (18.5%) were CIN 1 or normal.
Loop Electrosurgical Excision Procedure (LEEP) performed within the first 15 weeks of pregnancy in 67 women was safe. In 5.2% of pregnant women with CIN 2–3, the final diagnosis was invasive cancer.
HIT-EC: Trustworthy prediction of enzyme commission numbers using a hierarchical interpretable transformer
Authors: Dumontet Louis , Han So-Ra , Oh Tae-Jin , Kang Mingon 
Published: February 2025

AbstractAccurate and trustworthy prediction of Enzyme Commission (EC) numbers is critical for understanding enzyme functions and their roles in biological processes. Despite the success of recently proposed deep learning-based models, there remain limitations, such as low performance in underrepresented EC numbers, lack of learning strategy with incomplete annotations, and limited interpretability. To address these challenges, we propose a novel hierarchical interpretable transformer model, HIT-EC, for trustworthy EC number prediction. HIT-EC employs a four-level transformer architecture that aligns with the hierarchical structure of EC numbers, and leverages both local and global dependencies within protein sequences for this multi-label classification task. We also propose a novel learning strategy to handle incomplete EC numbers. HIT-EC, as an evidential deep learning model, produces trustworthy predictions by providing domain-specific evidence through a biologically meaningful interpretation scheme. The predictive performance of HIT-EC was assessed by multiple experiments: a cross-validation with a large dataset, a validation with external data, and a species-based performance evaluation. HIT-EC showed statistically significant improvement in predictive performance when compared to the current state-of-the-art benchmark models. HIT-EC’s robust interpretability was further validated by identifying well-known conserved motifs and functional regions in the CYP106A2 enzyme family. HIT-EC would be a robust, interpretable, and reliable solution for EC number prediction, with significant implications for enzymology, drug discovery, and metabolic engineering. The open-source code is publicly available at:https://github.com/datax-lab/HIT-EC.
Inverse Agonism of the FFA4 free fatty acid receptor controls both adipogenesis and mature adipocyte function
Authors: Alshammari WS , Duncan EM , Vita L , Kenawy M , Dibnah B , Wabitsch M , Gould G , Hudson BD 
Published: February 2025

AbstractAdipocyte disfunction is an important component of many metabolic disorders and there is a need for pharmacological approaches that can restore normal adipocyte function. The FFA4 receptor is a G protein coupled receptor (GPCR), activated by long chain free fatty acids (FFAs), that controls adipocyte function. Importantly, adipocytes produce FFAs, which may directly activate FFA4 and there is a need to better understand how FFAs produced by adipocytes interact with FFA4 signalling. In this study we have employed human and mouse adipocyte cell models to determine how pharmacological agonism or antagonism of FFA4 affects adipogenesis, lipolysis and glucose uptake. We show that a commonly used FFA4 antagonist, AH7614, is an inverse agonist and that treating adipocytes with this compound suppressed adipogenesis, inhibits glucose uptake and enhances isoprenaline stimulated lipolysis. In contrast, treatment with a synthetic FFA4 agonist, TUG-891, has only modest effects on adipogenesis and lipolysis, while showing no effect on glucose uptake. To explore the mechanism for why AH7614 but not TUG-891 affects adipocyte function, we demonstrate that during adipogenic differentiation sufficient FFAs are released into the culture medium to activate FFA4, suggesting AH7614 inhibits an autocrine feedback loop to suppress adipogenesis. In contrast, during lipolysis experiments, insufficient FFAs were released to activate the receptor, suggesting that AH7614 must enhance lipolysis by either inhibiting ligand independent FFA4 signalling, or FFA signalling that does not require the FFAs to be released from the cell. This study will help establish how FFA4 targeting therapeutics could be used to treat adipocyte dysfunction.
Lifetime changes in Body map based on music prediction
Authors: Tanaka Masaki , Daikoku Tatsuya 
Published: February 2025

SummaryThis study aims to investigate the relationship between music, which is said to promote well-being, and emotions as well as bodily sensations across the lifespan. Using eight chord progressions based on predictive models, we conducted online experiments with 784 participants aged 10 to 80, evaluating bodily sensation mapping and emotional responses. The results revealed that bodily sensations peaked in the 20s to 30s and subsequently declined with age, particularly for chords with low prediction error and uncertainty. On the other hand, arousal levels increased with age and showed a strong correlation with predictable musical structures. These findings suggest that bottom-up bodily responses diminish with ageing, while supporting the relationship between top-down processing shaped by accumulated experience and the predictability of music, as indicated by previous research. This study enhances the development of music-based interventions that improve well-being across generations, considering the unique physical and emotional characteristics of each age group.
A Mathematical Model for Chemo-mechanically Induced Collective Cell Motility on Planar Elastic Substrates
Authors: Ahmed Riham K. , Abdalrahman Tamer , Davies Neil H. , Vermolen Fred , Franz Thomas 
Published: February 2025

AbstractCells interact with mechanical and chemical environmental cues, such as mechanical cues from other cells and chemical signals from growth factors. The current study aims to develop a mathematical model for combined chemically and mechanically induced collective cell motility on planar substrates. In this model, an extension of a previous model simulates cell motility induced by strain energy density gradients in the planar substrate originating from cellular traction forces is presented to capture the effect of a growth factor gradient and describe chemo-mechanically induced deterministic collective cell motility on planar elastic substrates. Green’s function and Duhamel’s principle are used to solve the diffusion equation that describes the distribution of a growth factor and to represent chemo-mechanically induced deterministic collective cell motility on planar elastic substrates. The migratory displacement and velocity of a single cell towards the growth factor source on the elastic substrate are demonstrated for varying growth factor production and diffusion rates. Chemically induced motility of 25 cells towards the growth factor source is predicted for different growth factor production and diffusion rates. Chemo-mechanical cues with varying growth factor production and diffusion rates are explored for the motility of four cells and one motile cell in the presence of one stationary cell. The developed model describes the chemo-mechanically induced motility of individual cells on planar substrates. The model provides valuable information forin vivoorin vitrodue to its suitability for extension to other chemical source shapes, mobilized sources, many sources, and soluble concentration gradients.
scBSP: A fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data
Authors: Li Jinpu , Raina Mauminah , Wang Yiqing , Xu Chunhui , Su Li , Guo Qi , Ferreira Ricardo Melo , Eadon Michael T , Ma Qin , Wang Juexin , Xu Dong 
Published: February 2025

ABSTRACTEmerging spatial omics technologies empower comprehensive exploration of biological systems from multi-omics perspectives in their native tissue location in two and three- dimensional space. However, sparse sequencing capacity and growing spatial resolution in spatial omics present significant computational challenges in identifying biologically meaningful molecules that exhibit variable spatial distributions across different omics. We introduce scBSP, an open-source, versatile, and user-friendly package for identifying spatially variable features in high-resolution spatial omics data. scBSP leverages sparse matrix operation to significantly increase computational efficiency in both computational time and memory usage. In diverse spatial sequencing data and simulations, scBSP consistently and rapidly identifies spatially variable genes and spatially variable peaks across various sequencing techniques and spatial resolutions, handling two- and three-dimensional data with up to millions of cells. It can process high-definition spatial transcriptomics data for 19,950 genes across 181,367 spots within 10 seconds on a typical desktop computer, making it the fastest tool available for handling such high-resolution, sparse spatial omics data while maintaining high accuracy. In a case study of kidney disease using 10x Xenium data, scBSP identified spatially variable genes representative of critical pathological mechanisms associated with histology.
VAMP8 Deficiency Attenuates AngII-Induced Abdominal Aortic Aneurysm Formation via Platelet Reprogramming and Enhanced ECM Stability
Authors: Mohammadmoradi Shayan , Driehaus Elizabeth R. , Alfar Hammodah R. , Joshi Smita , Whiteheart Sidney W. 
Published: February 2025

ABSTRACTBACKGROUNDAs vascular sentries, platelets, and their ability to release a host of bioactive molecules, are critical for vascular homeostasis as well as hemostasis. Despite data linking platelet activation to abdominal aortic aneurysms (AAA) and rupture, the underlying mechanisms remain poorly understood. This study addresses the hypothesis that VAMP8, the primary v-SNARE controlling platelet exocytosis, contributes to AAA formation.METHODS AND RESULTSIn an AngII-infused hypercholesterolemic mouse model, we observed significant platelet consumption, indicated by decreased platelet counts at both acute (5-day) and chronic (28-day) time points. Platelets accumulated at sites of elastin degradation and within false lumens of the abdominal aorta after 28 days of AngII infusion. Bulk RNA sequencing analysis of washed platelets and their releasates after 5 days of AngII infusion revealed significant transcriptomic changes, suggesting rapid reprogramming of platelet function. Parallel RNA-seq analysis of suprarenal aortic tissue highlighted changes in genes associated with extracellular matrix (ECM) organization, inflammation, and platelet signaling, linking platelets to vascular remodeling suggesting a “platelet-aorta axis”. Laser speckle imaging in a FeCl₃ injury model confirmed that VAMP8 deficiency impaired platelet function, resulting in delayed thrombosis.In vivoexperiments demonstrated that VAMP8⁻/⁻ mice were protected against AngII-induced AAA and aortic rupture. Aortic diameter analysis further revealed that VAMP8 deficiency significantly attenuated AngII-driven aortic pathology. RNA-seq analysis of platelets and aortic tissue suggests that loss of VAMP8 affects expression of genes controlling ECM degradation and aortic wall stability consistent with the protective effect of VAMP8 loss on AAA.CONCLUSIONShort-term AngII infusion appears to reprogram the platelet transcriptome, which may affect the aorta and contribute to AAA formation. Controlling cargo release from platelets via VAMP8 deficiency results in profound attenuation of aortic aneurysms. This introduces a novel paradigm for understanding the impact of reprogrammed platelet cargo secretion and function in aortopathies.Graphical AbstractHighlightsPlatelet transcriptome is altered at early aneurysmal stage.VAMP8 deficiency attenuates aortic aneurysms, potentially via enhanced ECM stability.VAMP8 deficiency significantly alters various genes contributing to aortic wall structure and stability in both platelets and suprarenal aortic tissue.
Free-Form Microfluidic Microneedle Array Patches
Authors: Coates Ian A. , Driskill Madison M. , Rajesh Netra U. , Lipkowitz Gabriel , Ilyin Dan , Xu Yue , Dulay Maria T. , Jacobson Gunilla B. , Perry Jillian L. , Tian Shaomin , DeSimone Joseph M. 
Published: February 2025

AbstractPersonalized biomedical devices, such as microneedle array patches (MAPs), offer a promising transdermal drug delivery technology, providing a safe, painless, and self- administered alternative to traditional hypodermic injections. Despite their potential for precise therapeutic release, MAP adoption has been limited by challenges in payload capacity, treatment versatility, and manufacturing scalability. To address these issues, we integrated microfluidic channel designs with MAP technology, enhancing its functionality for delivering a range of payloads, from liquid therapeutics to solid-state cargos, at tunable volumes. Using injection continuous liquid interface production (iCLIP), a novel additive manufacturing approach, we fabricated high-resolution microfluidic MAPs with complex designs. Inspired by the stingers and fangs of various venomous animals, we developed a biomimetic microneedle design that prevents clogging, enhances mechanical strength, and eliminates needle leakage, thereby improving therapeutic delivery efficiency. Our technology reliably delivers multiple distinct payloads, enables combinational mixing, and enables point-of-care reconstitution of solid-state payloads.TeaserLeveraging biomimetic design and advanced 3D printing, we developed high-resolution microfluidic microneedle array patches (MAPs) that overcome payload and scalability challenges, offering a versatile and efficient platform for precise transdermal drug delivery.
A typology of Australian terrestrial bird communities
Authors: Maron Martine , Indraswari Karlina , Mills-Anderson Jonathan , Melton Courtney B. , Mayfield Helen J. , Possingham Hugh , Radford James , Reside April E. , Bennett Andrew , Burbidge Allan , Clarke Michael , Clarke Rohan H. , Davis Robert , Eyre Teresa , Freeman Amanda , Gibson Michelle , Hansen Birgita , Haslem Angie , Humphrey Jacinta , Jackett Nigel , Palmer Bryony , Kutt Alex , Leseberg Nicholas P. , Loyn Richard , Maisey Alex , Maurer Golo , McDonald Paul , Mihailou Helenna , Noske Richard , Rainsford Fred , Reid Julian , Robinson Doug , Selwood Katherine , Simmonds Jeremy S. , Spindler Rebecca , Teixeira Daniella , Tulloch Ayesha , Vanderduys Eric , Verdon Simon , Watson David , Watson James , Fraser Hannah 
Published: February 2025

ABSTRACTAimIncreasing interest in holistic measurement of the response of fauna communities to interventions requires suitable community condition metrics. However, the development of such metrics is hindered by the absence of broad-scale typologies at suitable spatial and ecological resolutions. We aimed to derive a preliminary typology of terrestrial bird communities for Australia, based on bird co-occurrence data, and describe and map the likely distribution of each community type across the continent.LocationMainland Australia, continental islandsTime period1973-2022Major taxa studiedAvesMethodsWe used fine-scale co-occurrence data from standard 2-ha surveys in BirdLife Australia’s citizen-science database. After filtering to reduce bias, we used hierarchical clustering followed by iterative consultation with experts to identify reliably distinct and recognisable terrestrial bird communities across Australia. We used Maxent to model the likely distributions of each community, and developed community descriptions based on each community’s composition and distribution.ResultsThe resultant typology included 29 reliably distinct and recognisable bird communities with major clusters corresponding with seven broad geographical regions. The distributions of bird communities did not correspond tightly to the boundaries of major vegetation groups, with most communities occurring across multiple vegetation types.Main ConclusionsOur preliminary typology of bird communities provides a standard classification at a continental scale. It newly defines distinct bird communities as entities for which condition benchmarks can be established to allow assessment of their conservation status and monitoring of change over time.Refinement will enable cryptic communities in areas with sparse data to be identified. The method could be translated to other regions where adequate coverage of data in the form of standardised surveys of fauna are available. Vast biodiversity datasets delivered through citizen science programs provide the opportunity to develop such typologies for fauna communities, as a precursor to developing targeted and informative community condition metrics.
Specimen-tailored “lived” climate reveals precipitation onset and amount best predict specimen phenology, but only weakly predict specimen reproductive success across a clade
Authors: Bontrager Megan G. , Worthy Samantha J. , Leventhal Laura C. , Maloof Julin A. , Gremer Jennifer R. , Schmitt Johanna , Strauss Sharon Y. 
Published: February 2025

SummaryHerbarium specimens are broadly distributed in space and time, enabling investigation of impacts of climate on phenology and persistence Many studies have revealed climate-associated phenological shifts; we ask which of temperature, precipitation, or the timing of precipitation onset best explain specimen phenological stage, and whether the same variables also explain specimen reproduction, a measure closely aligned with fitness.We calculated specimen-specific climate from estimated specimen germination date until average collection dates for 14 annual species ofStreptanthusandCaulanthus(Brassicaceae). We also test whether relationships of phenology and reproduction with climate variables are evolutionarily constrained.Precipitation amount and onset date predicted specimen phenology, but much less so, specimen reproductive success. Earlier rainfall onset was associated with more phenologically advanced specimens, a relationship that showed evolutionary conservatism; however, such advancement had little effect on specimen reproduction. This lack of correlation may arise from processes like phenological shifts that buffer fitness impacts of climate, interactions with other community members also responding to climate, or challenges in estimating total reproduction from herbarium specimens.We make suggestions for collection protocols that could improve the usefulness of herbarium data to understand climate impacts on reproduction, a better predictor than phenology of future population viability.
Actions of the Anti-Seizure Drug Carbamazepine in the Thalamic Reticular Nucleus: Potential Mechanism of Aggravating Absence Seizures
Authors: Jang Sung-Soo , Agranonik Nicole , Huguenard John R. 
Published: February 2025

AbstractCarbamazepine (CBZ) is a widely used antiepileptic drug effective in managing partial and generalized tonic-clonic seizures. Despite its established therapeutic efficacy, CBZ has been reported to worsen seizures in another form of epilepsy, generalized absence seizures, in both clinical and experimental settings. In this study, we focused on thalamic reticular (RT) neurons, which regulate thalamocortical network activity in absence seizures, to investigate whether CBZ alters their excitability, thereby contributing to the exacerbation of seizures. Using ex vivo whole-cell patch-clamp electrophysiology, we found that CBZ selectively inhibits the tonic firing of RT neurons in a dose-dependent manner without affecting burst firing. At the RT-thalamocortical (RT-TC) synapse, CBZ significantly increases the failure rate of GABAergic synaptic transmission, with greater effects on somatostatin (SST) – than parvalbumin (PV) - expressing RT neurons. In vivo EEG recordings and open-field behavior in Scn8amed+/-mouse model confirmed that CBZ treatment exacerbates absence seizures, increasing both seizure frequency and duration while reducing locomotor activity. In addition, CBZ further amplifies the pre-existing reduction in tonic firing of RT in Scn8amed+/-mice. These findings uncover a novel mechanism by which CBZ exacerbates absence seizures through selective inhibition of RT neuron excitability and disruption of GABAergic synaptic transmission. This work provides mechanistic insights into the paradoxical effects of CBZ and suggest potential avenues for optimizing epilepsy treatment strategies.Scientific SignificanceThis study addresses the clinical paradox in which CBZ, a widely prescribed antiepileptic drug, paradoxically aggravates absence seizures. Understanding the cellular mechanisms behind this phenomenon is critical for improving epilepsy treatments. Here, using electrophysiology recordings from intact thalamocortical slices and SCN8amed+/-mice, an absence seizure animal model, we demonstrate that CBZ selectively inhibits tonic firing of RT neurons and their output to thalamocortical circuits, with a more pronounced effect in SCN8amed+/-mice. These novel findings provide a mechanistic explanation for CBZ’s paradoxical aggravation of absence seizures, offering a framework for understanding the pharmacological effects of other anti-epilepsy drugs and guiding the development of more effective therapeutic strategies for epilepsy.
Filamented Light (FLight) Bioprinting of Mini-Muscles with Self-Renewal Potential
Authors: Liu Hao , Winkelbauer Michael , Janiak Jakub , Kalkan Ali Kerem , Kim Inseon , Chansoria Parth , Bar-Nur Ori , Zenobi-Wong Marcy 
Published: February 2025

AbstractThe plasticity and regenerative capacity of skeletal muscle arise from quiescent stem cells activated upon overload, injury, or inflammation. Developingin vitromuscle models to study these properties could advance muscle disease modeling and pre-clinical evaluation. Here, we leverage Filamented Light (FLight) bioprinting as a high-throughput approach for producing mini-muscle tissues. Using Pax7-nGFP myoblasts, we bioprinted mini-muscles from pristine collagen-fibrinogen. The FLight hydrogel consisted of aligned microstructures which guided the formation of aligned myotubes. Mini-muscles demonstratedin vivo-like tissue organization, including highly aligned myotubes and a Pax7+cell pool embedded in newly deposited laminin. Both spontaneous and electrically stimulated contractions were observed. Collagen-fibrinogen matrix was promising for maintenance of the Pax7+cell pool. Damage from cardiotoxin-induced injury of the mini-muscles led to a massive proliferation of Pax7+cells and restoration of the contractile properties. Notably, small molecules such as Repsox could enhance regeneration. FLight printed mini-muscles have potential for applications in muscle biology, exercise/atrophy, disease models, and drug screening.