bluuebunny/crossref_metadata_2025 huggingface dataset:
β3 accelerates microtubule plus end maturation through a divergent lateral interface
Authors: Wood Lisa M. , Moore Jeffrey K.
Published: January 2025

β-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents. In HeLa cells, β3 overexpression decreases the lifetime of microtubule growth, and this requires residues at the lateral interface. These microtubules exhibit a shorter region of EB binding at the plus end, suggesting faster lattice maturation, and resist stabilization by paclitaxel. Resistance requires the H1-S2 and H2-S3 regions at the lateral interface of β3. Our results identify the mechanistic origins of the unique activity of β3 tubulin and suggest that tubulin isotype expression may tune the rate of lattice maturation at growing microtubule plus ends in cells.

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A neo-Durkheimian institutional theory of buffering
Authors: 6 Perri , Heims Eva
Published: January 2025

Sustaining cooperation during deepening mistrust requires very specific organizational dynamics in government, to cultivate—for example—both ‘realist’ and ‘liberal institutionalist’ capabilities, and find a workable relationship between them in policymaking, negotiation and implementation. This presents an acute problem of coordination, requiring ‘buffering’. The chapter presents a neo-Durkheimian institutional theory of varieties of buffering, showing that understanding how it can work is a key part of understanding why it is attempted and often achieved. It shows how informal institutional ordering cultivates styles of judgement in government, which in turn shape stances towards status in international affairs. Finally, using this theory, the chapter presents our hypotheses about trends over the period examined in Chapters 3–7.
The zenith of negotiation, 1875–1898
Authors: 6 Perri , Heims Eva
Published: January 2025

A more negotiated form of buffering emerged from 1879 through the 1880s. This chapter considers debates in British government about the lack of any ‘state’s interest’ clause in submarine cable landing concessions, which revealed major problems of lack of coordination between security and commercial considerations. It goes on to examine internal government negotiations as well as diplomatic talks which led to the second adherence decision, to the Submarine Cable Convention of 1884, showing how negotiated buffering shaped decision-making. The following section shows how the the theory explains British decision-making on the Pacific Cable proposal. The chapter challenges the standard view of the ‘war reservation clause’. Finally, it shows how changed buffering shaped British strategy at ITU conferences.
‘No in English I don’t do that’: exploring Gambian migrants’ linguistic cooperation in Italy
Authors: Santello Marco
Published: January 2025

This study explores the experience of linguistic cooperation of migrants, focussing on their varying degrees of reliance on others for communication. It adopts an approach that draws theoretically on innovations in the understanding of competence beyond the cognitive-structuralist paradigm and more broadly on the importance of cooperation in the social sphere. Based on the lived experience of Gambian migrants in a shelter as it emerges interactionally between the researcher and three participants, the data show that asking for help can be problematic, and reliance on others changes over time and depending on the tasks and languages involved. Furthermore, when migrants lean on others it is not necessarily long-standing social networks that complement one’s competence but also fleeting encounters, and online tools for individual language learning can be useful when cooperation is not there. Competence beyond individual skills needs to be further researched, so that gradation in cooperation, the use of material affordances and different stances towards reliance on others, as well as where they stem from, are more fully accounted for.
Separation of Three Polar Compounds with Similar Polarities from Swertia mussotii by a Combination of Two Counter-Current Chromatography Modes
Authors: Li Hongmei , Chen Tao , Shen Cheng , Wang Shuo , Luo Juyuan , Song Zhibo , Ma Yumei , Li Aijing , Lu Weihang , Feng Hailun , Li Yulin
Published: January 2025

Separation of polar compounds especially with similar polarities is challenging. In the present study, three polar compounds with similar polarities, including gentiopicroside, sweroside and mangiferin, have been successfully separated from Swertia mussotii by a combination of two counter-current chromatography modes. With the selected solvent system of ethyl acetate/n-butanol/water (8/2/10, v/v), a continuous injection mode was firstly employed. As a result, 10.4 g of mangiferin with purity higher than 98% and 8 g of Peak I mainly composed of gentiopicroside and sweroside could be easily obtained from 24 g of the sample by counter-current chromatography through eight injections. Then, a recycling counter-current chromatography mode was introduced for the separation of gentiopicroside and sweroside. Through six cycles, 5.3 g of gentiopicroside and 0.8 g of sweroside with purity higher than 98% were obtained from 8 g of Peak I. The research provides a reference for the large-scale separation of polar compounds with similar polarities.
Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study
Authors: Vena Antonio , Tiseo Giusy , Falcone Marco , Bartalucci Claudia , Marelli Cristina , Cesaretti Mario , Di Pilato Vincenzo , Escribano Pilar , Forniti Arianna , Giacobbe Daniele Roberto , Guinea Jesus , Limongelli Alessandro , Lupetti Antonella , Machado Marina , Mikulska Malgorzata , Salmanton-García Jon , Soriano-Martin Ana , Taramasso Lucia , Valerio Maricela , Bouza Emilio , Muñoz Patricia , Bassetti Matteo
Published: January 2025

Background

This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI).

Methods

A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included.

Results

Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year; 95% confidence interval [CI], 1.01–1.05; P = .0005), solid tumor (aHR 1.91; 95% CI, 1.06–3.46; P = .0302), previous antifungal treatment (aHR 1.84; 95% CI, 1.12–3.10; P = .0192), and septic shock (aHR 2.39; 95% CI, 1.42–4.06; P = .0010), but not fluconazole resistance (aHR 1.00; 95% CI, .62–1.63; P = .9864) nor the type of initial antifungal therapy (aHR 1.46; 95% CI, .69–3.06; P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81; 95% CI, .37–1.75; P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37; 95% CI, 2.11–25.80; P = .0018).

Conclusions

Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.
Guidelines for Gene and Genome Assembly Nomenclature
Authors: Cannon Ethalinda K S , Molik David C , Wright Adam J , Zhang Huiting , Honaas Loren , Chougule Kapeel , Dyer Sarah
Published: January 2025

The rapid increase in the number of reference-quality genome assemblies presents significant new opportunities for genomic research. However, the absence of standardized naming conventions for genome assemblies and annotations across datasets creates substantial challenges. Inconsistent naming hinders the identification of correct assemblies, complicates the integration of bioinformatics pipelines, and makes it difficult to link assemblies across multiple resources. To address this, we developed a specification for standardizing the naming of reference genome assemblies, to improve consistency across datasets and facilitate interoperability. This specification was created with FAIR (Findable, Accessible, Interoperable, and Reusable) practices in mind, ensuring that reference assemblies are easier to locate, access, and reuse across research communities. Additionally, it has been designed to comply with primary genomic data repositories, including members of the International Nucleotide Sequence Database Collaboration (INSDC) consortium, ensuring compatibility with widely used databases. While initially tailored to the agricultural genomics community, the specification is adaptable for use across different taxa. Widespread adoption of this standardized nomenclature would streamline assembly management, better enable cross-species analyses, and improve the reproducibility of research. It would also enhance natural language processing applications that depend on consistent reference assembly names in genomic literature, promoting greater integration and automated analysis of genomic data. This is a good time to consider more consistent genomic data nomenclature as many research communities and data resources are now finding themselves juggling multiple datasets from multiple data providers.
A Matter of Individual Discretion: Facilitating Performative Credibility in Asylum Interviews
Authors: Bodström Erna
Published: January 2025

This article discusses performative credibility in asylum interviews, which are regarded as the most important single event in the asylum process. Despite this importance, and although there are studies that focus on asylum interviews, there is very little research regarding how the interviews are facilitated – that is, how the interviewers guide the interview through the introduction they provide, the questions they ask, and the order in which they ask those questions. The current article contributes to filling this gap by looking at asylum interviews as performances, in which the right to seek asylum is decided not only by what the applicant says but also by how they say it. The article calls this expectation placed upon the asylum applicant ‘performative credibility’. The article asks how asylum interviews facilitate performative credibility, and answers this question by analysing the discourses of facilitation and question orders in 43 asylum interview records from the Finnish Immigration Service. The findings indicate that facilitation is uncommon in the interviews, that there is no all-encompassing way of going about it, and that it happens largely at the discretion of the individual interviewer. This means that, while a small number of applicants are facilitated, others may not even be made aware of the roles and rules of performative credibility, including that their performance is assessed during the interview, meaning that these applicants are left in a disadvantaged position. The current article seeks to make an important contribution to the field of refugee studies by showing how asylum interviews can facilitate – or not – the kinds of detailed and coherent narratives assessed to be credible and truthful in asylum decision making.
Trends in single-fraction palliative radiotherapy across the COVID-19 pandemic in Japan: a nationwide claims study
Authors: Koide Yutaro , Aoyama Takahiro , Noguchi Masamune , Shindo Yurika , Kitagawa Tomoki , Shimizu Hidetoshi , Hashimoto Shingo , Tachibana Hiroyuki , Kodaira Takeshi
Published: January 2025

This study aimed to evaluate the recent trends in single-fraction conventional radiotherapy (CRT) as palliative treatment in Japan, using data from the National Database published by the Ministry of Health, Labor, and Welfare. Data from fiscal year (FY) 2014 to FY2022, specifically related to the utilization of single-fraction CRT, were analyzed. Multi-fraction CRT, stereotactic body radiotherapy (SBRT), intensity-modulated radiotherapy (IMRT), and brachytherapy were excluded. The primary outcome was the cumulative and annual number of single-fraction CRT courses. Additionally, quarterly course data from FY2019 to FY2022, the period for which monthly data were available, were assessed to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on single-fraction CRT utilization. Of the total 2 315 607 radiotherapy courses, we identified 33 221 single-fraction CRT courses after excluding multi-fraction CRT (n = 1 835 650), SBRT (n = 33 935), IMRT (n = 332 827), and brachytherapy (n = 113 195). The annual number of single-fraction CRT courses increased from 1730 in FY2014 to 5642 in FY2022, with an average annual growth rate of 0.28 (range: −0.07 to 0.65). Outpatient courses significantly increased, particularly from FY2019 onward, surpassing inpatient courses in FY2022 (2914 vs 2728). The highest annual increase was observed in FY2020, particularly from April to December, although this upward trend did not persist in 2021. In conclusion, single-fraction CRT has exhibited a consistent upward trend, highlighting its expanding role in palliative radiotherapy. Although the COVID-19 pandemic temporarily accelerated this trend, its impact has already subsided, with growth rates returning to pre-pandemic levels.
Calibration and applications of the all-sky camera at the Ali Observatory in Tibet
Authors: Yin Jia , Yao Yongqiang , Qian Xuan , Liu Liyong , Chen Xu , Zhai Liuming
Published: January 2025

A high-precision calibration method for all-sky cameras has been realized using images from the Ali observatory in Tibet, providing application results for atmospheric extinction, night sky brightness, and known variable stars. This method achieves high-precision calibration for individual all-sky images, with the calibration process introducing deviations of less than 0.5 pixels. Within a 70-deg zenith angle, the calibration deviation of the images is less than 0.25 pixels. Beyond this angle, the calibration deviation increases significantly due to the sparser distribution of stars. Increasing the number of stars with zenith angles greater than 70 deg used for calibration can improve the calibration accuracy for areas beyond the 70-deg zenith angle, reducing the calibration deviation at an 85-deg zenith angle to 0.2 pixels. Analysis of the all-sky images indicates that the atmospheric extinction coefficient at the Ali Observatory is approximately 0.20, and the night sky background brightness is about 21 mag per square arcsec, suggesting the presence of urban light pollution.
Exon location of glycine substitutions impacts kidney survival in autosomal dominant Alport Syndrome
Authors: Pagniez Marie-Sophie , Fages Victor , Gatinois Clémence , Larrue Romain , Pottier Nicolas , Laboux Timothée , Lenain Rémi , Grunewald Olivier , Robert Thomas , Rigothier Claire , Mesnard Laurent , Glowacki François
Published: January 2025

Background and hypothesis

Unlike X-linked or autosomal recessive Alport Syndrome, no clear genotype/phenotype correlation has yet been demonstrated in patients carrying a single variant of COL4A3 or COL4A4.

Methods

We carried out a multicenter retrospective study to assess the risk factors involved in renal survival in patients presenting a single pathogenic variant on COL4A3 or COL4A4.

Results

97 patients presenting a single pathogenic variant of COL4A3 or COL4A4 were included. The prevalence of end-stage kidney disease (ESKD) during follow-up was 28.7% (median age 47.5 years [IQR, 39.1–55.8]). 23 patients carried a ‘severe’ mutation (frameshift, stop gain, extensive deletion, impacting splicing), and 60 patients presented a glycine substitution in a collagenous domain. In patients with glycine missense variants, the location of the mutation in the distal exons was associated with worse renal survival with a more pronounced decline in eGFR compared to variants in proximal exons. Conversely, the presence of a severe mutation did not impact renal survival.

Conclusion

Our results confirm that ADAS can lead to ESKD. We demonstrated that a glycine substitution involving the distal exons had a negative impact on renal survival in ADAS patients, probably due to a trimerization defect. This could help improve personalized follow-up in ADAS patients with glycine substitution and could be integrated to a future prognostic score to accurately predict renal outcomes.
Born of frustration: the emergence of Camelina sativa as a platform for lipid biotechnology
Authors: Haslam Richard P , Michaelson Louise V , Eastmond Peter J , Napier Johnathan A
Published: January 2025

The emerging crop Camelina sativa (L.) Crantz (camelina) is a Brassicaceae oilseed with a rapidly growing reputation for the deployment of advanced lipid biotechnology and metabolic engineering. Camelina is recognized by agronomists for its traits, including yield, oil/protein content, drought tolerance, limited input requirements, plasticity, and resilience. Its utility as a platform for metabolic engineering was then quickly recognized, and biotechnologists have benefited from its short life cycle and facile genetic transformation, producing numerous transgenic interventions to modify seed lipid content and generate novel products. The desire to work with a plant that is both a model and crop has driven the expansion of research resources for camelina, including increased availability of genome and other -omics data sets. Collectively, the expansion of these resources has established camelina as an ideal plant to study the regulation of lipid metabolism and genetic improvement. Furthermore, the unique characteristics of camelina enables the design-build-test-learn cycle to be transitioned from the controlled environment to the field. Complex metabolic engineering to synthesize and accumulate high levels of novel fatty acids and modified oils in seeds can be deployed, tested, and undergo rounds of iteration in agronomically relevant environments. Engineered camelina oils are now increasingly being developed and used to sustainably supply improved nutrition, feed, biofuels, and fossil fuel replacements for high-value chemical products. In this review, we provide a summary of seed fatty acid synthesis and oil assembly in camelina, highlighting how discovery research in camelina supports the advance of metabolic engineering toward the predictive manipulation of metabolism to produce desirable bio-based products. Further examples of innovation in camelina seed lipid engineering and crop improvement are then provided, describing how technologies (e.g. genetic modification [GM], gene editing [GE], RNAi, alongside GM and GE stacking) can be applied to produce new products and denude undesirable traits. Focusing on the production of long chain polyunsaturated omega-3 fatty acids in camelina, we describe how lipid biotechnology can transition from discovery to a commercial prototype. The prospects to produce structured triacylglycerol with fatty acids in specified stereospecific positions are also discussed, alongside the future outlook for the agronomic uptake of camelina lipid biotechnology.
The requisite intention for constituting a Quistclose trust
Authors: Tam Anfield
Published: January 2025

In China Life Trustees Ltd v China Energy Reserve and Chemical Group Overseas Co Ltd [2024] HKCFA 15, the Hong Kong Court of Final Appeal clarified that a positive intention for the transferor to retain beneficial interest in the transferred assets is not necessary for a Quistclose trust to arise. Rather, it suffices when the parties intended the transferred assets to be used exclusively for a specific purpose, such that it is not at the transferee’s free disposal. This note appraises the decision for disentangling the conceptual nuances between these two types of intention. The Court rightly held that the transferor’s retention of beneficial interest is merely a legal consequence of the restrictive intention, as on a correct reading of the authorities such retention need not be intended for a Quistclose trust to arise.
Intravascular Lithotripsy for Coronary Artery Calcification: An Expert Review
Authors: Agrawal Ankit , Gupta Rahul , Arockiam Aro Daniela , Bhagat Umesh , Chandna Sanya , Aronow Wilbert S. , Frishman William H. , Sharma Samin K.
Published: January 2025

Coronary artery calcification is an impediment to percutaneous coronary interventions by obstructing the device pathway or stent deployment. To facilitate percutaneous coronary intervention in such complex lesions, high-pressure balloon dilations, atherectomy procedures, and specialty balloons are used but they all come with considerable limitations and periprocedural complications like dissection and perforation. To surpass these disadvantages, intravascular lithotripsy was introduced which acts by delivering high-pressure pulsatile sonic waves circumferentially thereby destroying the calcium deposits. It is a safe and effective treatment modality in treating severe coronary artery calcification and facilitating stent delivery with minimal complications.
Extending empirical dynamic modeling to cross-sectional data beyond traditional time series
Authors: Deyle Ethan R. , Pao Gerald , Sugihara George
Published: January 2025

The foundation of Empirical dynamic modeling (EDM) is in representing time-series data as the trajectory of a dynamic system in a multidimensional state space rather than as a collection of traces of individual variables changing through time. Takens’s theorem provides a rigorous basis for adopting this state-space view of time-series data even from just a single time series, but there is considerable additional value to building out a state space with explicit covariates. Multivariate EDM case studies to-date, however, generally rely on building up understanding first from univariate to multivariate and use lag-coordinate embeddings for critical steps along the path of analysis. Here, we propose an alternative set of steps for multivariate EDM analysis when the traditional roadmap is not practicable. The general approach borrows ideas of random data projection from compressed sensing, but additional justification is described within the framework of Takens’s theorem. We then detail algorithms that implement this alternative method and validate through application to simulated model data. The model demonstrations are constructed to explicitly demonstrate the possibility for this approach to extend EDM application from time-series trajectories to effectively realizations of the underlying vector field, i.e. data sets that measure change over time with very short formal time series but are otherwise “big” in terms of number of variables and samples.
Decline of Antimicrobial Resistance inPseudomonas aeruginosaBacteremia Following the COVID-19 Pandemic: a Longitudinal Observational Study
Authors: Butscheid Yulia , Frey Pascal M. , Pfister Marc , Pagani Lisa , Kouyos Roger D. , Scheier Thomas C. , Staiger Willy I. , Mancini Stefano , Brugger Silvio D.
Published: January 2025

Background

Multidrug-resistant Pseudomonas aeruginosa (MDRPA) poses significant challenges in hospital settings. Understanding the effects of the unprecedented changes brought by the COVID-19 pandemic on antimicrobial resistance in P. aeruginosa (PA) is essential to inform stewardship efforts. This study investigated the dynamics of antimicrobial resistance in PA bacteremia after the start of the pandemic.

Methods

This single-centre retrospective cohort study included adult inpatients with PA bacteraemia at the University Hospital Zurich between January 2014 and December 2023. Data were retrieved from electronic records. The primary outcome was the association between the start of the COVID-19 pandemic and PA with MDR, defined as resistance to ≥3 of 5 antibiotic classes. We used logistic regression to adjust for age, sex and ICU treatment, accounting for multiple bacteremia instances within the same patient using cluster-robust standard errors. Secondary outcomes included changes in resistance patterns and patient demographics, with antimicrobial exposure assessed as median monthly days of therapy (DOT).

Results

A total of 493 instances of PA bacteremia in 333 patients were observed during the study period. The proportion of MDRPA declined from 21% (62/291) pre-pandemic to 9% (19/202) post-pandemic (adjusted OR 0.38, 95% CI 0.18–0.79, p=0.01). The occurrence of MDRPA during hospitalisation following an initial instance of non-MDRPA bacteremia was rare and unlikely to happen earlier than after two weeks. Antimicrobial consumption patterns shifted after the start of the pandemic, with reduced use of amikacin and ciprofloxacin and increased use of cefepime and meropenem. Overall inhospital-mortality among patients with MDRPA bacteraemia remained high (28%), with no substantial differences before and after the pandemic (adjusted hazard ratio 1.57, 95% CI 0.43–5.67, p=0.49).

Conclusion

We observed a decline in MDRPA occurrence after the start of the COVID-19 pandemic, possibly driven by intensified infection control measures, shifts in antimicrobial use, and changes in patient populations.
COSIME: Cooperative multi-view integration and Scalable and Interpretable Model Explainer
Authors: Choi Jerome J. , Cohen Kalafut Noah , Gruenloh Tim , Engelman Corinne D. , Lu Tianyuan , Wang Daifeng
Published: January 2025

Single-omics approaches often provide a limited view of complex biological systems, whereas multiomics integration offers a more comprehensive understanding by combining diverse data views. However, integrating heterogeneous data types and interpreting the intricate relationships between biological features—both within and across different data views—remains a bottleneck. To address these challenges, we introduce COSIME (Cooperative Multi-view Integration and Scalable Interpretable Model Explainer). COSIME uses backpropagation of Learnable Optimal Transport (LOT) to deep neural networks, enabling the learning of latent features from multiple views to predict disease phenotypes. In addition, COSIME incorporates Monte Carlo sampling to efficiently estimate Shapley values and Shapley-Taylor indices, enabling the assessment of both feature importance and their pairwise interactions—synergistically or antagonistically—in predicting disease phenotypes. We applied COSIME to both simulated data and real-world datasets, including single-cell transcriptomics, single-cell spatial transcriptomics, epigenomics, and metabolomics, specifically for Alzheimer’s disease-related phenotypes. Our results demonstrate that COSIME significantly improves prediction performance while offering enhanced interpretability of feature relationships. For example, we identified that synergistic interactions between microglia and astrocyte genes associated with AD are more likely to be active at the edges of the middle temporal gyrus as indicated by spatial locations. Finally, COSIME is open-source and available for general use.
RNA3DClust: segmentation of RNA three-dimensional structures using a clustering-based approach
Authors: Le Quoc Khang , Angel Eric , Tahi Fariza , Postic Guillaume
Published: January 2025

A growing body of evidence shows that the biological activity of RNA molecules is not only due to their primary and secondary structures, but also to their spatial conformation. As the experimental determination of the three-dimensional (3D) structure is a costly and uncertain process, the development of computational methods for predicting RNA fold is a necessity. A critical task for 3D structure prediction consists of finding substructures that can be predicted independently, before being assembled into a global fold. In protein structures, these subparts are the “structural domains” and, to the best of our knowledge, no equivalent concept has ever been defined for RNA macromolecules.

In this work, we present RNA3DClust, an adaptation of the Mean Shift clustering algorithm to the RNA 3D structure partitioning problem. This approach allowed us to delimit compact and separate regions in RNA conformations, analogously to the seminal definition of domains in proteins. Developing RNA3DClust required us to create a dataset of RNA 3D domain annotations, as well as a new segmentation quality score, which we both used for evaluating our method. In addition to macromolecular geometry, we also show that the RNA domain decompositions produced by RNA3DClust are relevant regarding data about RNA biological function reported in the literature. Finally, the emerging interest in long non-coding RNAs (lncRNAs) and their likeliness of containing locally folded regions has motivated us to generate an additional reference dataset of lncRNA predicted conformations. The resulting delineations of 3D domains by RNA3DClust illustrate the potential of our method for analyzing lncRNAs. Source code and datasets are freely available for download on the EvryRNA platform at:https://evryrna.ibisc.univ-evry.fr.
Modification of Non-photochemical Quenching Pathways in the C4Model PlantSetaria viridisRevealed Shared and Unique Photoprotection Mechanisms as Compared to C3Plants
Authors: Milburn Grace , Morris Cheyenne M. , Kosola Eileen , Patel-Tupper Dhruv , Liu Jian , Pham Dominique H. , Acosta-Gamboa Lucia , Stone William D. , Pardi Sarah , Hillman Kylee , McHargue William E. , Becker Eric , Kang Xiaojun , Sumner Josh , Bailey Catherine , Thielen Peter M. , Jander Georg , Kane Cade N. , McAdam Scott A. M. , Lawton Thomas J. , Nusinow Dmitri A. , Zhang Feng , Gore Michael A. , Cheng Jianlin , Niyogi Krishna K. , Zhang Ru
Published: January 2025

Light is essential for photosynthesis; however, excess light can increase the accumulation of photoinhibitory reactive oxygen species that reduce photosynthetic efficiency. Plants have evolved photoprotective non-photochemical quenching (NPQ) pathways to dissipate excess light energy. In tobacco and soybean (C3plants), overexpression of three NPQ genes,violaxanthin de-epoxidase (VDE),Photosystem II Subunit S(PsbS), andzeaxanthin epoxidase(ZEP), hereafter VPZ, resulted in faster NPQ induction and relaxation kinetics, and increased crop yields in field conditions. NPQ is well-studied in C3plants; however, NPQ and the translatability of the VPZ approach in C4plants is poorly understood. The green foxtailSetaria viridisis an excellent model to study photosynthesis and photoprotection in C4plants. To understand the regulation of NPQ and photosynthesis in C4plants, we performed transient overexpression in Setaria protoplasts and generated (and employed) stable transgenic Setaria plants overexpressing one of the three Arabidopsis NPQ genes or all three NPQ genes (AtVPZ lines). Overexpressing (OE)AtVDEandAtZEPin Setaria produced similar results as in C3plants, with increased or reduced zeaxanthin (thus NPQ), respectively. However, overexpressingAtPsbSappeared to be challenging in Setaria, with largely reduced NPQ in protoplasts and under-represented homozygous AtPsbS-OE lines, potentially due to competitive and tight heterodimerization of AtPsbS and SvPsbS proteins. Furthermore, Setaria AtVPZ lines had increased zeaxanthin, faster NPQ induction, higher NPQ level, but slower NPQ relaxation. Despite this, AtVPZ lines had improved growth as compared to wildtype under several conditions, especially high temperatures, which is not related to the faster relaxation of NPQ but may be attributable to increased zeaxanthin and NPQ in C4plants. Our results identified shared and unique characteristics of the NPQ pathway in C4model Setaria as compared to C3plants and provide insights to improve C4crop yields under fluctuating environmental conditions.
Accurate Prediction of Protein Complex Stoichiometry by Integrating AlphaFold3 and Template Information
Authors: Liu Jian , Neupane Pawan , Cheng Jianlin
Published: January 2025

Protein structure prediction methods require stoichiometry information (i.e., subunit counts) to predict the quaternary structure of protein complexes. However, this information is often unavailable, making stoichiometry prediction crucial for complexes with unknown stoichiometry. Despite its importance, few computational methods address this challenge. In this study, we present an approach that integrates AlphaFold3 structure predictions with homologous template data to predict stoichiometry. The method generates candidate stoichiometries, builds structural models for them using AlphaFold3, ranks them based on AlphaFold3 scores, and further refine predictions with template-based information when available. In the 16th community-wide Critical Assessment of Techniques for Protein Structure Prediction (CASP16), our method achieved 71.4% top-1 accuracy and 92.9% top-3 accuracy, outperforming other predictors in terms of the overall performance. This demonstrates the complementary strengths of AlphaFold3- and template-based predictions and highlights its applicability for uncharacterized protein complexes lacking stoichiometry data.
Expanding the phenotype spectrum of β-mannosidosis
Authors: Martin-Rios Angela , Stepien Karolina M , Gibbs Liliane H. , Hall Katherine , Hall Patricia L. , Pino Gisele Bentz , Wang Raymond , Pillai Nishitha R. , Lund Troy C. , Orchard Paul J. , Kimonis Virginia
Published: January 2025

Purpose

To expand the spectrum of clinical and biochemical phenotypes, and brain imaging features of individuals with β-mannosidosis, a rare lysosomal storage disease.

Methods

We describe the clinical features of six patients with β-mannosidosis, their findings on brain magnetic resonance imaging (MRI), and the changes over time in two of them. We also review previously reported patients, analyze the variants inMANBA,the first symptom and spectrum of symptoms, and the ages of onset and of diagnosis of the disease.

Results

Forty-four patients have been reported to date, including our patients. The mean age of diagnosis is 12.8 years, and the age of onset of symptoms is 2.4 years. Hearing loss is the most frequently reported initial symptom and intellectual disability is the most frequent symptom overall. Erythromelalgia, nystagmus, macrocephaly, and obsessive-compulsive-like behavior are newly described features associated with β-mannosidosis. 40% of the patients have abnormal brain imaging. Brain MRI showed hypomyelination in one patient and abnormal white matter changes in another patient. Twenty-nine pathogenic variants inMANBAhave been reported among the 44 patients; 60.6% of patients have private variants, and 39.4% have the recurrent variant c.2158-2A>G. A new oligosaccharide structure: Neu-Man2-GlcNac2, was found in the urine of two affected patients.

Conclusion

Due to disease heterogeneity, establishing a genotype-phenotype correlation remains challenging in β-mannosidosis. A spectrum of brain MRI abnormalities are described as manifestations of this condition: delayed myelination, hypomyelination, and abnormal white matter signals. Additional studies are needed to delineate the pathophysiology of this condition.
Pseudo-p-Value-Based Clumping Enhanced Proteome-wide Mendelian Randomization with Application in Identifying Coronary Heart Disease-Associated Plasma Proteins
Authors: Wang Yuquan , Cao Yunlong , Chen Dong , Shi Dapeng , Fu Liwan , Chen Anqi , Shen Siyuan , Hu Yue-Qing
Published: January 2025

Mendelian randomization (MR) is a powerful tool for causal inference in epidemiology. However, the presence of weak instrumental variables (IVs) and pleiotropy can lead to biased causal effect estimates. To address these issues, we develop MR-GMM, a novel MR method based on a Gaussian Mixture Model. MR-GMM classifies IVs into four categories—invalid, valid, invalid&null, and null IVs— and models their effects using a two-dimensional spike-and-slab distribution. Simulation studies demonstrate the high efficiency and robustness of MR-GMM compared to existing methods. More importantly, we propose a pseudo-p-value-based linkage disequilibrium (LD) clumping procedure to address selection bias. This refined procedure is capable of enhancing the performance of MR-GMM as well as many existing MR methods in real-world scenarios. Applying MR-GMM in a large-scale proteome-wide MR study, we identify 45 coronary heart disease-associated plasma proteins. Subsequent network and enrichment analyses highlight the potential of these proteins as biomarkers for disease diagnosis and therapeutic development.
Associations of Serum Folate and Vitamin B12levels with Cardiovascular Mortality among Non-diabetic Population
Authors: Chen Zijun , Cheng Dian , Wang Xuecheng
Published: January 2025

Background

While studies have examined the associations between folate, vitamin B12, and cardiovascular mortality in high-risk populations, evidence regarding these associations in non-diabetic population remains limited. This study aimed to assess the associations of serum folate and vitamin B12levels with cardiovascular mortality in a large, nationally representative cohort of US non-diabetic adults.

Methods and Results

Data were extracted from the National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2006 and 2011 to 2014. Multivariate logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the associations between serum folate, vitamin B12and cardiovascular mortality. A two-piecewise logistic regression model was employed to identify the inflection points of serum folate and vitamin B12levels on cardiovascular mortality. Among 19,402 US adults, the mean age was 43.9 ± 18.6 years, 9,749 (50.2%) were male, and 8,438 (43.5%) were non-Hispanic White. With a median follow-up of 159 months (IQR: 82.0-193.0 months), 928 cardiovascular deaths were documented. After fully adjusting for potential confounders, a significant inverse association was observed between serum folate levels and cardiovascular mortality. The RCS analysis revealed non-linear associations between serum folate (Pfor nonlinearity = 0.02), vitamin B12levels (Pfor nonlinearity = 0.04), and the risk of cardiovascular mortality. Specifically, serum folate levels below 19.50 ng/mL and serum vitamin B12levels at or above 436.52 pg/mL were both linked to an increased risk of cardiovascular mortality. Stratified and sensitivity analyses confirmed the robustness of these associations.

Conclusions

This study demonstrated that low serum folate levels and high vitamin B12levels were associated with an increased risk of cardiovascular mortality in non-diabetic individuals. These findings provide evidence supporting the potential of serum folate and vitamin B12levels as biomarkers for cardiovascular mortality risk estimation, pending further validation in other independent cohorts.
Carotid endarterectomy is associated with lower rates of reintervention compared to carotid stenting
Authors: Adkar Shaunak S. , George Elizabeth L. , Zheng Xinyan , Sorondo Sabina M. , Fereydooni Arash , Dossabhoy Shernaz , Stern Jordan R.
Published: January 2025

Objectives

Perioperative outcomes for carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) have been well studied. Less is known about the durability and reintervention rates of each, particularly in the era of transcarotid artery revascularization (TCAR). We sought to compare real-world rates of ipsilateral reintervention, stroke, and death in patients undergoing CEA, TFCAS, and TCAR.

Methods

The Vascular Quality Initiative (VQI) was matched to Medicare claims via the Vascular Implant Surveillance and Implantation Network (VISION) database to identify patients who had primary carotid revascularization from December 2016 to December 2019 in a n observational cohort study. The primary outcome was ipsilateral reintervention; secondary outcomes included stroke and mortality. After 1:1 greedy matching using propensity scores, patients who underwent CEA and carotid artery stenting (CAS) via either transcarotid or transfemoral approach were compared using time-dependent Cox regression models. A separate propensity matched analysis was then performed to compare TFCAS and TCAR. Kaplan-Meier curves were compared using log rank tests.

Results

After propensity matching (N=27,944 patients), we compared 4705 patients in each group. Risk of re-intervention was increased within 6 months for CAS (HR: 1.97; 95% CI: 1.11-3.50; p<0.05), but not beyond 6 months (HR: 1.08; 95% CI: 0.62-1.89; p=0.79). The incidence of stroke prior to discharge was increased in patients undergoing CAS (5.4% v. 1.0%; p<0.0001) and mortality hazard with CAS was increased both within 6 months (HR:1.69; 95% CI: 1.38- 2.07; p<0.0001) and beyond 6 months (HR: 1.52; 95% CI: 1.27-1.81; p<0.0001). When comparing TFCAS and TCAR (n=2115 per group), there was a significantly increased risk of re- intervention for TFCAS beyond 6 months (HR: 2.31, 95% CI: 1.05-5.11, p <0.05).

Conclusions

CEA portends a lower risk of reintervention than CAS, particularly within the first 6 months after revascularization. On subgroup analysis of stenting modalities, TCAR had a lower hazard of longer-term reintervention compared to TFCAS.
Characterising the periodontal granulation tissue using scRNAseq
Authors: Zhu Wentao , Fung Kathy , Dhami Pawan , Sharpe Paul , Krivanek Jan , Nibali Luigi , Zhang Cheng , Neves Vitor C.M.
Published: January 2025

Aims

Our research investigated the cellular composition and molecular mechanisms of periodontal granulation tissue using single-cell RNA sequencing (scRNA-seq), aiming to enhance the understanding of periodontal disease pathogenesis and identify potential targets for regenerative therapies.

Materials and Methods

Granulation tissue samples were collected from patients undergoing periodontal surgery. Fresh tissues were processed into single-cell suspensions and subjected to scRNA-seq. The data were integrated with existing datasets from healthy gingiva and periodontal ligament. Computational analyses were performed, and validation through immunofluorescence staining.

Results

Ten distinct cell clusters were identified across the samples. Granulation tissue exhibited a higher abundance of immune cells compared to healthy tissues. A novel endothelial cell subpopulation, exclusive to granulation tissue, was discovered, characterized by NOTCH3 expression and involvement in ossification pathways. Additionally, granulation tissue Fibroblast subpopulations demonstrated a progenitor-like state, characterized by extracellular matrix reorganization and low differentiation, similar to cancer-associated fibroblasts.

Conclusion(s)

This study advances the understanding of periodontal disease by characterizing key regulatory cell populations within granulation tissue. The identification of the novel endothelial subpopulation offers new insights into the disease’s pathogenesis and presents potential targets for regenerative therapies. These findings suggest opportunities for developing biomaterials that modulate specific cellular pathways to improve periodontal disease treatment.
Using high-dimensional immunophenotyping for mapping immune cell composition in rapid cryopreserved liquid biopsies
Authors: Pedersen JG , Jordt JCL , Thorborg E , Dietz LL , Winther-Larsen A , Gammelgaard KR , Jakobsen MR
Published: January 2025

Liquid biopsies, such as a blood sample, are non-invasive and simple ways to monitor biomarkers in clinical settings. For cancer immunotherapy settings a major clinical goal is to identify host immunological biomarkers that can be used to monitor progression of disease, treatment efficacy, or even adverse effects. Here, the profiling and validation of blood circulating immune cells may allow continuously survey on how the immune system alters during disease progress and treatment. However, such practice will require proper sampling and development of a robust high-dimensional phenotypic analysis.

Here, we designed a 37-marker spectral flow cytometry assay with the purpose of conducting high-dimensional immunophenotyping as monitoring the immune status in patients. The assay was developed to profile all major immune cell compartments, their differentiation as well as activation markers, including numerous checkpoint markers. Importantly, we validated this assay in context of how liquid biopsies should be processed to ensure minimal effect of cryopreservation compared to immunophenotyping of a freshly acquired blood sample. Our work highlights important considerations for which phenotypic alternations can be introduced with different cryopreservation methods. Essentially, we identified a fast and simple processing pipeline where cryopreservation of immune cells showed minimal changes in the immunophenotyping profile. This approach can certainly be implemented in clinical settings and will help diagnostic clinical sites with a strong and validated tool applicable for monitoring individual patients’ immunological status.
The first complete mitochondrial genome of the endangered spotted eagle rayAetobatus ocellatus
Authors: Marín Alan
Published: January 2025

The complete mitochondrial genome of the endangered spotted eagle rayAetobatus ocellatuswas determined for the first time using Next Generation Sequencing (NGS) reads mined from the Sequence Read Archive (SRA) of the GenBank database (BioSample SAMN31811701, collection site: Bohol Island, Philippines). The spotted eagle ray mitogenome (GenBank accession pending) has 20,217 bp in length displaying a typical vertebrate mitogenome organization (13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region). A phylogenetic analysis based on the nucleotide sequence information of 13 protein-coding genes from different related species confirmed the species status ofA. ocellatusas an Indo-West Pacific species, which was formerly described asA. narinariwhose current accepted distribution is restricted to the Atlantic Ocean.