bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychosocial Determinants and Outcomes of Expedited Liver Transplant Evaluations: Insights From a Retrospective Cohort Analysis
Authors: Cooper Katherine M. , Srivoleti Padmavathi , Colletta Alessandro , Tripp Doris , Mehta Savant , Movahedi Babak , Devuni Deepika 
Published: January 2025

Background.
As the burden of chronic liver disease and the demand for liver transplants (LT) grows, understanding the interplay between access to care and patient outcomes is increasingly important. In this study, we explored patient characteristics and transplant outcomes in patients undergoing LT evaluations, with a focus on identifying risk factors for expedited LT evaluation.

Methods.
This single-center retrospective cohort study included patients who underwent LT evaluation for deceased donor LT between October 2017 and July 2021. Patients were categorized by context: expedited (inpatient) and routine (outpatient) LT evaluation groups. The outcome measures included waitlist status, pre-LT mortality, and post-LT complications.

Results.
Of 602 patients, 26% underwent expedited LT evaluation. Patients who underwent expedited evaluation were more likely to have a history of ascites (P < 0.001), hepatic encephalopathy (P < 0.001), and spontaneous bacterial peritonitis (P < 0.001) and had a higher model for end-stage liver disease sodium scores (P < 0.001). Both mortality (35% versus 17%, P < 0.001) and LT (39% versus 22%, P < 0.001) were more common in the expedited group; post-LT mortality was similar up to 2 y. Perceived financial concerns and social security disability income were risk factors for expedited LT evaluation. In addition, greater proximity to the LT center (95% confidence interval, 1.1-6.3; P = 0.025) and speaking a primary language other than English (95% confidence interval, 1.0-10.7; P = 0.042) were risk factors for expedited LT evaluation in women but not in men.

Conclusions.
Expedited LT evaluations were associated with more severe illness and higher pre-LT mortality; however, post-LT outcomes were comparable with those of routine evaluations. Identifying psychosocial risk factors may enhance equity and access to LT evaluations, particularly for women who face unique challenges in this context.
Prevalence and Clinical Associations of Peripapillary Hyperreflective Ovoid Mass-like Structures in Craniosynostosis
Authors: Jeon-Chapman Jacqueline G. , Estrela Tais , Zurakowski David , Chang Yoon-Hee , Dagi Linda R. , Gise Ryan A. 
Published: January 2025

Background:
Patients with craniosynostosis are at high risk of developing elevated intracranial pressure (ICP) causing papilledema and secondary optic atrophy. Diagnosing and monitoring optic neuropathy is challenging because of multiple causes of vision loss including exposure keratopathy, amblyopia, and cognitive delays that limit examination. Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are an optical coherence tomography (OCT) finding reported in association with papilledema and optic neuropathy. We investigated the prevalence of PHOMS in patients with syndromic craniosynostosis and the relationship with known risk factors of optic neuropathy.

Methods:
This was a cross-sectional retrospective study was performed at Boston Children's Hospital and included 118 eyes (60 patients) with syndromic craniosynostosis that had at least one good quality optic nerve OCT volumetry scan between January 2010 and December 2023. Testing was reviewed by 2 neuro-ophthalmologists to determine the presence of PHOMS. Information collected included demographics, and clinical course including possible Chiari malformation, obstructive sleep apnea (OSA), history of elevated ICP, best-corrected visual acuity (VA), spherical equivalent (SE), retinal nerve fiber layer thickness, macular ganglion cell layer volume, and funduscopic examination. Our primary outcome measure was presence of PHOMS, and secondary outcome measure was the relationship between clinical characteristics and the presence of PHOMS.

Results:
Mean age at imaged OCT was 9.8 ± 5.2 years and 41/60 (68.3%) patients were female. The prevalence of PHOMS was 17/60 patients (28.3%) or 26/118 eyes (22.0%), higher than previously reported in children without craniosynostosis (P < 0.001). PHOMS were significantly associated with a history of elevated ICP (odds ratio [OR] 14.4, 95% CI: 1.9–111.0, P < 0.001) and with concurrent papilledema (OR 40.4, 95% CI: 6.6–248.0, P < 0.001). OSA, Chiari malformation, best-corrected VA, craniosynostosis variant, and SE were not independently associated with PHOMS.

Conclusions:
Eyes in children with craniosynostosis had a higher prevalence of PHOMS than reported in children without craniosynostosis. PHOMS were significantly more common with a history of elevated ICP and with concurrent papilledema. PHOMS may serve as a clinically useful indicator of optic neuropathy, and of recurrence of papilledema in patients with craniosynostosis and in other populations characterized by multiple sources of vision loss and cognitive changes that limit evaluation.
Xist RNA Dependent and Independent Mechanisms Regulate Dynamic X Chromosome Inactivation in B Lymphocytes
Authors: Toothacre Natalie E. , Rodríguez-Acevedo Kiara L. , Wiggins Keenan J. , Scharer Christopher D. , Anguera Montserrat C. 
Published: January 2025

SUMMARYX-Chromosome Inactivation (XCI) involves epigenetic pathways to equalize X-linked gene expression between female and male mammals. XCI is dynamic in female B cells, as cytological enrichment of Xist RNA and heterochromatic marks on the inactive X-chromosome (Xi) are absent in naïve B cells yet return following mitogenic stimulation. Here, we asked whether any heterochromatic histone marks are present on the Xi in naïve B cells, and whether Xist RNA is required for their deposition and retention following stimulation. We find that the Xi in naïve B cells is depleted for H2AK119Ub and H3K9me3 but enriched for DNA methylation and H3K27me3, which maintain an Xist RNA-dependent epigenetic memory of XCI. Upon stimulation, Xist-independent H3K27me3 and Xist-dependent H2AK119Ub modifications accumulate across the Xi with temporal and spatial specificity. Our findings reveal the importance of Xist RNA, H3K27me3, and H2AK119Ub marks for the epigenetic integrity of X-linked genes across the Xi following female B cell stimulation.
JRSeek: Artificial Intelligence Meets Jelly Roll Fold Classification in Viruses
Authors: Sanchez Jason E. , Guo Wenhan , Li Chunqiang , Li Lin , Xiao Chuan 
Published: January 2025

AbstractThe jelly roll (JR) fold is the most common structural motif found in the capsid and nucleocapsid of viruses. Its pervasiveness across many different viral families motives developing a tool to predict its presence from a sequence. In the current work, logistic regression (LR) models trained on six different large language model (LLM) embeddings exhibited over 95% accuracy in differentiating JR from non-JR sequences. The dataset used for training and testing included sequences from single JR viruses, non-JR viruses, and non-virus immunoglobulin-like β-sandwich (IGLBS) proteins which closely resemble the JR fold in structure. The high accuracy is particularly remarkable given the low sequence similarity across viral families and the balanced nature of the dataset. Also, the accuracy of the models was independent of LLM embeddings, suggesting that peak accuracy for predicting viral JR folds hinges more on the data quality and quantity rather than on the specific mathematical models used. Given that many viral capsid and nucleocapsid structures have yet to be resolved, using sequence-based LLMs is a promising strategy that can readily be applied to available data. Principal Component Analysis of the Bert-U100 embeddings demonstrates that most IGLBS sequences and a subset of JR and non-JR sequences are distinguishable even before the application of the LR model, but the LR model is necessary to differentiate a subset of more ambiguous sequences. When applied to double JR folds, the Bert-U100 model was able to assign the JR motif for some viral families, providing evidence for the model’s generalizability. However, for other families, this generalizability was not observed, motivating a future need to develop other models informed by double JR folds. Lastly, the Bert-U100 model was also able to predict whether sequences from a dataset of unclassified viruses produce the JR fold. Two examples are given and the JR predictions are corroborated by AlphaFold3. Altogether, this work demonstrates that JR folds can, in principle, be predicted from their sequences.
Therapeutic ability of extracellular vesicles derived from angio-miRNA-modified mesenchymal stromal cells in ischemic animal models
Authors: Wada Yoshiki , Kudo Toshifumi , Kusakabe Tomomi , Inoue Ayako , Yoshioka Yusuke , Ochiya Takahiro , Fukuda Shoji 
Published: January 2025

AbstractBackgroundRegenerative therapy using extracellular vesicles (EVs) is expected to be an option for supportive therapy of chronic limb-threatening ischemia. In this study, we examined the angiogenic potential of EVs derived from genetically modified MSCs, focusing on the angio-miRNAs in these vesicles.MethodsBone marrow mesenchymal stromal cells (BM-MSCs) were transfected with a lentiviral vector containing specific angio-miRNAs (miRNA-126, -135b, or -210). EVs were separated from the culture medium of BM-MSCs via ultracentrifugation. The quality and quantity of the EVs were evaluated using nanoparticle tracking analysis, fluorometry, and an ExoScreen assay. Tube formation assays were conducted using human umbilical vein endothelial cells to assess the angiogenic potency of the EVsin vitro. The EVs were injected into the ischemic hind limb muscles of mice. The grades of limb ischemia, blood perfusion, and muscle tissues were analyzed to assess the angiogenic potency of the EVsin vivo.ResultsAngio-miRNAs were overexpressed in MSCs transfected with a lentiviral vector. Tube formation was significantly enhanced when endothelial cells were cultured with the EVs (P < 0.05). Compared to non-contact co-culture with BM-MSCs, EVs derived from modified BM-MSCs significantly promoted tube formation in endothelial cells (P < 0.05). The severity of limb ischemia on day 7 was alleviated when a combination of two or three EVs derived from modified BM-MSCs was injected compared with native EVs. Toe blood perfusion on day 14 significantly recovered when a combination of two or three EVs derived from modified BM-MSCs was injected (P < 0.05). Tissue analysis revealed that the number of newly formed endothelial cells in ischemic muscles increased when a combination of two or three EVs derived from modified BM-MSCs was injected.ConclusionsThe use of a combination of EVs derived from genetically modified MSCs stimulated angiogenesis bothin vitroandin vivo.
Genotype-Dependent Response to Water Deficit: Increases in Maize Cell Wall Digestibility Occurs Through Reducing Both p-Coumaric Acid and Lignification of the Rind
Authors: López-Malvar Ana , Main Oscar , Guillaume Sophie , Jacquemot Marie-Pierre , Meunier Florence , Revilla Pedro , Santiago Rogelio , Mechin Valerie , Reymond Matthieu 
Published: January 2025

AbstractThe compositional dynamics of the cell wall are influenced by drought, and it has been demonstrated that water deficit induces significant changes in its main components. Moreover, changes in cell wall concentration and distribution in response to water deficit affect maize degradability. This study presents a histological and biochemical analysis of thirteen maize inbred lines, evaluated over two years in Pobra de Brollón (Spain) and Mauguio (France) under contrasting water availability conditions. Our aim was to investigate the environmental and genotypic impacts on histological and biochemical profiles, to assess in vitro cell wall digestibility under water deficit, and to explore how these responses relate to changes in cell wall composition and structure. Overall, we observed greater concentrations of p-coumaric acid under control conditions, with significant decreases in stressed conditions at each location. Histologically, we found an increase in non-lignified tissues under water deficit conditions across all tissues and in both locations. In terms of in vitro cell wall digestibility (IVCWRD), significant increases were detected in response to water deficit. Additionally, genotype-dependent response patterns were evident, revealing two distinct behavioural groups. Notably, in plastic genotypes, increases in IVCWRD in response to water deficit were concomitant to reductions in p-coumaric acid content and a decrease in red-stained lignified tissues in the rind. This study emphasizes the complex, genotype-dependent responses to water deficit, underscoring the important roles of plasticity and stability in shaping the impact on maize cell wall digestibility; paving the way to breed for adapted genotypes to face climate changes.HighlightIncreased digestibility in response to water deficit is genotype-dependent and linked to reductions in p-coumaric acid content and lower lignification of the rind
Long Noncoding RNA Mir17hg and D43Rik Control the Macrophage Response toToxoplasma gondiiInfection
Authors: Doherty Claire M. , Belmares-Ortega Jessica , Haskins Breanne E. , Menard Kayla L. 
Published: January 2025

AbstractLong noncoding (lnc) RNAs are emerging as imported regulators of immunity but how they impact the host response to infection is still largely unknown. In previous screening studies we identified Mir17hg and D43Rik as host lncRNAs upregulated in mouse bone marrow-derived macrophages regardless of parasite strain type. Here, we examined the impact of Mir17hg and D43Rik during infection of macrophages. Expression of these lncRNAs was transiently increased byT. gondii, peaking 6 hr post infection and falling to background noninfected levels by 18 hrs. Both Mir17hg and D43Rik were predominantly localized to the host cell nucleus, suggesting roles in gene regulation. Using a lncRNA silencing approach mediated by siRNA, we uncovered evidence that both D43Rik and Mir17hg were involved in modulating the host transcriptional response to infection with Type I and Type II strains ofToxoplasma. These effects were most dramatic during infection with the high virulence Type I RH, where Mir17hg silencing resulted in increased expression of a broad panel of immunity-related genes. Our results implicate lncRNAs Mir17hg and D43Rik as important molecular regulators of the macrophage response toToxoplasma.
Heartbeat-like dynamics drives oxygen activation in methane monooxygenase
Authors: Hwang Yunha , Ryu Bumhan , Lee Dong-Heon , Hong Hyo Jin , Na Jeong-Geol , Song Chul Gyu , Kang Hyun Goo , Pozharski Edwin , Lee Seung Jae 
Published: January 2025

ABSTRACTSoluble methane monooxygenase (sMMO) is an enzyme that hydroxylates methane (CH4), a potent greenhouse gas, at non-heme di-iron active sites under atmospheric conditions. The regulatory component (MMOB) is essential for the catalytic activity of hydroxylase (MMOH) as it induces conformational changes in the active site and facilitating substrate ingress. Recent advances in cryogenic electron microscopy (cryo-EM) have enabled us to elucidate the high resolution picture of sMMO catalytic mechanism. We describe the 2.85 Å cryo-EM structure of MMOH–MMOB, with one equivalent of MMOB bound to MMOH (H-1B), which is in contrast with previously solved crystal structures. MMOB allosterically regulates the MMOH protomer (αβγ) and induces conformational changes that propagate from the surface to the di-iron coordination site. TheN-terminal region of the MMOH β-subunit (NT-Hβ) stabilizes helices essential for iron coordination and oxygen activation. The MMOB-bound protomer (HBA, αβγB) presents the first structural report of a 2.7 Å Fe···Fe distance, while the non-MMOB-bound protomer (HBB, αβγ) and MMOH display a 3.1 Å distance. The coordination of Fe–ligands is maintained by the structural stabilization provided by the β- and γ-subunits of MMOH. This novel cryo-EM structure reveals new coordination environments, offering crucial mechanistic insights into sMMO catalysis.
Arms race of physical defences: Hooked trichomes ofMacarangaant-plants kill lycaenid caterpillars, but one specialist has a counter-defence
Authors: Chowdhury Ritabrata , Grafe Ulmar , Metali Faizah , Federle Walter 
Published: January 2025

AbstractThe co-evolution of insects and chemical plant defences has been described as an arms-race, but it is unclear if physical plant defences can produce similar outcomes. Here we report a previously unknown interaction from the mutualism between ants andMacarangatrees. AlthoughMacarangatrees are well protected against herbivory by aggressive ants, caterpillars of the genusArhopala(Lepidoptera: Lycaenidae) can feed on the leaves by appeasing the ants with nectar-like secretions. One ant-plant species,M. trachyphylla, bears hooked trichomes on its green surfaces. When placed onM. trachyphyllastems or petioles,Arhopalacaterpillars associated with otherMacarangaspecies (A. major, A. dajagakaandA. zylda) were quickly arrested by the sharp trichomes which pierced their cuticle, resulting in rapid loss of blood and death. In striking contrast,A. amphimutacaterpillars, which occur naturally onM. trachyphylla, could easily walk over the hooked trichomes without any injury. As hooked trichomes are a novel trait withinMacaranga, this interaction provides an example ofde novoevolution of a physical plant defence, which in turn has been overcome by a specialist herbivore. Our study suggests that physical plant defences can lead to evolutionary arms races similar to those for chemical defences.
Ancient biases in phenotype production drove the functional evolution of a protein family
Authors: Herrera-Álvarez Santiago , Patton Jaeda E. J. , Thornton Joseph W. 
Published: January 2025

ABSTRACTBiological systems may be biased in the phenotypes they can access by mutation1–7, but the extent of these biases and their causal role in the evolution of extant phenotypic diversity remains unclear. There are three major challenges: it is difficult to isolate the effect of bias in the genotype-phenotype (GP) map from that of natural selection in producing natural diversity6,8–11, the universe of possible genotypes and phenotypes is so vast and complex that a direct characterization has been impossible, and most extant phenotypes evolved long ago in species whose GP maps cannot be recovered. Here we develop exhaustive multi-phenotype deep mutational scanning to experimentally characterize the complete GP maps of two reconstructed ancestral steroid receptor proteins, which existed during an ancient phylogenetic interval when a new phenotype—specific binding of a new DNA response element—evolved12. We measured all possible DNA specificity phenotypes encoded by all possible amino acid combinations at sites in the protein’s DNA binding interface. We found that the ancestral GP maps are structured by strong global bias—unequal propensity to encode the various phenotypes—and extreme heterogeneity in the phenotypes accessible around each genotype, which strongly affect evolution on both long and short timescales. Distinct biases in the two ancestral maps steered evolution toward the lineage-specific functional phenotypes that evolved during history. Our findings establish that ancient biases in the GP relationship were causal factors in the evolutionary process that produced the present-day patterns of phenotypic conservation and diversity in this protein family.
Structural Basis for OAS2 Regulation and its Antiviral Function
Authors: Merold Veronika , Bekere Indra , Kretschmer Stefanie , Schnell Adrian F. , Kmiec Dorota , Sivarajan Rinu , Lammens Katja , Liu Rou , Mergner Julia , Teppert Julia , Hirschenberger Maximilian , Hammes Sarah , Buder Kathrin , Weitz Marcus , Koenig Lars M. , Pichlmair Andreas , Schwierz Nadine , Sparrer Konstantin M.J. , Lee-Kirsch Min Ae , de Oliveira Mann Carina C. 
Published: January 2025

SummaryOligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and critical for restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2’-5’-oligoadenylates for RNase L activation. Existing structures of OAS1 provide a model for enzyme activation, but do not explain how multiple OAS domains discriminate RNA length. Here, we discover that OAS2 exists in an autoinhibited state as a zinc-mediated dimer and present a mechanism for RNA length discrimination: the catalytically deficient domain acts as a molecular ruler that prevents autoreactivity to short RNAs. We demonstrate that dimerization and myristoylation localize OAS2 to Golgi membranes and that this is required for OAS2 activation and restriction of viruses that exploit the endomembrane system for replication, e.g. coronaviruses. Finally, our results highlight the non-redundant role of OAS proteins and emphasize the clinical relevance of OAS2 by identifying a patient with a loss-of-function mutation leading to autoimmune disease.
Dataset on Temperature Dependency of Zebrafish Early Development
Authors: Miller Angelina , Schröder Katja Lisa , Braun Karsten Eike , Steindorf Caitlin , Ottermanns Richard , Roß-Nickoll Martina , Backhaus Thomas 
Published: January 2025

AbstractZebrafish (Danio rerio) early development stages that do not feed independently, are classified as non-protected life stages under EU Directive 2010/63. Zebrafish reach the independently feeding stage not earlier than 120 hours post fertilization, depending on the incubation temperature. This paper presents a dataset documenting zebrafish early development at two commonly used temperatures 26 °C and 28 °C. We recorded onset of heartbeat and hatching as well as body length, eye size, yolk sac consumption, and swim bladder inflation. Additionally, locomotor activity was tracked after 96 and 119 hours post fertilization.The dataset serves as a baseline for selecting appropriate experimental conditions and optimizing toxicological study designs. They also facilitate the comparison of experimental results that were recorded at different temperatures. Furthermore, the data provide empirical evidence for amending current guidelines for tests with zebrafish embryos, in particular moving away from a rigid 120 hours post fertilization maximum test duration towards a temperature-dependent maximum test duration that is still in line with the aims of the German Animal Welfare Act.
Split-Small GTPase Reassembly as a Method to Control Cellular Signaling with User-Defined Inputs
Authors: He Yuchen , Faulkner Benjamin M. , Hyun Emily , Stains Cliff I. 
Published: January 2025

AbstractSmall GTPases are critical signaling enzymes that control diverse cellular functions such as cell migration and proliferation. However, dissecting the roles of these enzymes in cellular signaling is hindered by the lack of a plug-and-play methodology for the direct, temporal control of small GTPase activity using user-defined inputs. Herein, we present a method that pairs split-GTPases with user-defined chemical inducer of dimerization (CID) systems in a plug-and-play manner to directly control small GTPase signaling in living cells. The modularity of split-small GTPase systems allows for the selection of CIDs with minimal off-target effects on the pathway being studied. Our results highlight the ability to obtain consistent pathway activation with varying CID systems for direct control of MAPK signaling, filopodia formation, and cell retraction. Thus, split-small GTPase systems provide a customizable platform for development of temporally gated systems for directly controlling cellular signaling with user-defined inputs.