bluuebunny/crossref_metadata_2025 huggingface dataset:
Seed-Borne Endophytic Bacteria of Tomato – Dynamic Colonization and Implication in Plant Health
Authors: Lengrand Salomé , Dubois Benjamin , Renoz François , Lebbe Olivier , Debode Frédéric , Legrève Anne
Published: February 2025

Seed-borne endophytic bacteria are essential for seed germination, plant growth and stress tolerance. However, their functional diversity remains elusive due to difficulties in maintaining sterile conditions and amplifying bacterial community without amplifying plant genome. Using tomato (Solanum lycopersicum L.) as a model, we designed a novel culture system to study this bacterial community from seed to seedling, investigating their colonization and impact on plant health. Our workflow combined metabarcoding and culture-based approaches to capture the most accurate picture of the tomato seed-associated bacteria. Advanced metabarcoding protocol, involving sequencing of the 16S-ITS-23S rrn operon and the use of a newly designed tomato-specific Peptide Nucleic Acid (PNA) clamp var. Moneymaker, revealed a core microbiota consistently transmitted from seeds to shoots and roots. Key bacteria included Ralstonia picketti, Sphingomonas aerolata, Bradyrhizobium sp., Paucibacter aquatile, Microbacterium sp. and Stenotrophomonas sp. Culture-dependent approaches isolated endophytic strains, like Rummeliibacillus stabekisii, Peribacillus frigoritolerans and Pseudomonas protegens, which increase plant osmotic stress resistance. Using quantitative PCR, confocal microscopy and colony counting, we demonstrated that P. protegens tagged with mCherry colonizes root, shoot, and leaf tissues. Overall, our study supports the hypothesis that a rich and stable core of endophytic bacteria, capable of enhancing drought resistance, is transferred from seeds to plant organs. Our study provides the most detailed investigation to date of the diversity of the seed-borne microbial community of tomato and offers new approaches to better assess the diversity of plant-associated microorganisms, a key step towards leveraging it to improve crop resistance and productivity.
Pediatric antiphospholipid syndrome: expanding our understanding of antiphospholipid syndrome in children
Authors: Lewis Kevin , Tambralli Ajay , Madison Jacqueline A.
Published: February 2025

Purpose of review

Antiphospholipid syndrome (APS) is an autoimmune, thromboinflammatory disease, which affects children and adults. There are particular features of the disease and nuances to diagnosis and management in a pediatric population, which must be appreciated to improve clinical care.

Recent findings

Pediatric-specific epidemiological studies highlight that pediatric APS is quite rare with incidence in some populations of 0.2 per 100 000. There are new classification criteria in APS, which include a wider range of clinical features increasingly identified in registry data and case series of pediatric APS, though validation in pediatric APS is still needed. There is a particularly high proportion of pediatric APS patients with noncriteria antiphospholipid antibodies (aPL). Recurrent thrombosis is especially common in pediatric APS, highlighting the difficulty of management of this disease with high morbidity in children.

Recent research has enhanced understanding of pediatric-specific APS epidemiology, laboratory findings, the wide variety of clinical features, and challenges in successful treatment. Future directions could include evaluation of potentially unique features in pediatric pathophysiology, an evaluation of the new APS classification criteria in children, broader prospective data on clinical and laboratory features, and a continued search for treatment beyond committing young patients to lifelong anticoagulation.
Travelers From the Intestine to the Skin: A Useful Clue to Diagnose a Cryptic Histoplasma Infection
Authors: Frigo Emanuele , Lammertyn Astrid , Reyn Birgit , Garmyn Marjan , Hauben Esther , Maria Bosisio Francesca
Published: February 2025

A 53-year-old woman from Missouri (United States) with a 2-year history of kidney transplant presented to our dermatology department with multiple acneiform lesions on the face and numerous erythematous papules and nodules on both arms and legs. Biopsies revealed a very atypical florid pseudoepitheliomatous hyperplasia, at first interpreted, in light of the history of immunosuppression, as an invasive squamocellular carcinoma, associated with an unusual dense histiocytic infiltrate and nodular aggregates of foamy histiocytes. After the acute onset of fever, pancytopenia, and signs of ulcerative colitis, disseminated histoplasmosis was suspected. A biopsy taken from a rectal ulcer revealed numerous histiocytes with intracellular yeasts that were positive for periodic acid-Schiff and Grocott–Gomori methenamine silver fungal stains. Antifungal therapy with amphotericin B and itraconazole led to the healing of the skin lesions with scarring and postinflammatory hyperpigmentation. This case is an exceptional example that warns pathologists that (1) florid pseudoepitheliomatous hyperplasia can be undistinguishable from invasive squamocellular carcinoma, and complete excision of fast-growing lesions is always advised in case of doubt; (2) a dense infiltrate of foamy histiocytes may be the spy to a systemic infection, and a careful clinical and pathologic screening should be promptly initiated.
Tiered Accountability and Elements of an Effective Compliance Program Within High Reliability Organizations
Authors: Ibata Brent
Published: February 2025

Tiered accountability and the seven elements of an effective compliance program provide a scalable framework for enterprise risk management within high reliability healthcare organizations (HROs). However, these elements do not self-assemble into a mature system. They must be intentionally built into an effective compliance program that assesses, controls, and manages risks at an ongoing enterprise level. This starts with good governance from the governing body and passes through the organization’s chief executive officer into a psychologically safe, fair, and just culture that embraces imperfections as teaching moments. In an HRO, detected deviances from desired practices are seen as opportunities to embark on short excursions of self-improvement on the longer journey toward zero events of preventable harm.

The Centers for Medicare & Medicaid Services (CMS) and the US Department of Justice (DOJ) have published regulations and guidance that require and encourage organizations to proactively manage risk, with tiered accountability written into the CMS hospital conditions of participation (COP) and strongly encouraged in the DOJ newly revised Compliance Program Guidance containing its seven essential elements of an effective compliance program. Both CMS and the DOJ utilize a mixture of incentives and consequences to incentivize proactive risk management and compel reactive risk reduction. In these toolboxes of incentives and consequences, proactive healthcare executives can find the standards and rules to engineer and build highly reliable enterprise risk management systems with tiered accountability and risk-based talent management that focus available resources on high-risk, high-volume, and problem-prone areas.
Practical Utility of Serum Ammonia in Children With Acute Liver Failure: A Biomarker of Outcome
Authors: Abdullatif Hala Mohsen , Weigel Katharina , Verma Anita , Deep Akash , Dhawan Anil
Published: February 2025

Background.

Hyperammonemia is a recognized biochemical abnormality in acute liver failure (ALF). Our aim was to determine a cutoff value for serum ammonia in children with ALF to predict their outcomes while conventional UK liver transplant (LT) listing criteria were applied.

Methods.

We reviewed and analyzed the data of 68 patients with ALF who presented to our center from January 2014 to December 2018; inherited defects of ammonia metabolism were excluded. Patients were divided into 3 groups: Gr 1, LT (30 patients); Gr2, native liver survival (27 patients); and Gr 3, mortality (11 patients).

Results.

Highest ammonia levels during admission before intervention were higher in the LT and mortality group than in the native liver survival group (P = 0.011) with levels of 140 µmol/L showing a specificity of 100% as a predictor for LT/mortality. Sixty-two percent of patients with ALF developed encephalopathy; grades 3 and 4 in almost one-third. Encephalopathy was more common in Gr1 patients, followed by Gr3, whereas Gr2 were the least likely to develop encephalopathy. Ammonia levels were significantly higher in encephalopathic patients than in nonencephalopathic (P = 0.001). Serum ammonia of 80.5 µmol/L predicted encephalopathy with 80% sensitivity and 75% specificity.

Conclusions.

Serum ammonia level of >80 µmol/L can be used as an alert to ongoing encephalopathy although encephalopathy signs may be missing or subtle and a surrogate marker for earlier interventions for extracorporeal therapies. Moreover, levels >140 µmol/L predict the need for LT or death.
Saturation kinetics and specificity of transporters for L-arginine and asymmetric dimethylarginine (ADMA) at the blood-brain and blood-CSF barriers.
Authors: Fidanboylu Mehmet , Thomas Sarah Ann
Published: February 2025

Nitric oxide synthases (NOS) synthesize nitric oxide (NO) from L-arginine in endothelial and neuronal cells.  Asymmetric dimethylarginine (ADMA) is a homologue of arginine and an endogenous inhibitor of NOS.  As NO is a critical signalling molecule and influences physiological pathways in health and disease, the transfer of arginine and ADMA across the blood-CNS barriers is of interest.  Our research group have previously demonstrated the presence of saturable transporters for [3H]-L-arginine and [3H]-ADMA at the blood-brain and blood-CSF barriers using in vitro and in situ methods.  In this study, we determine the identity and kinetic characteristics of these transporters by means of the in situ brain/choroid plexus perfusion technique in anaesthetised mice.  Results indicated that [3H]-arginine and [3H]-ADMA could be transported across blood-brain and blood-CSF barriers by the cationic amino acid transporter, system-y+.  In contrast to the results obtained with arginine where transport was predominately by a single transport system (system-y+), ADMA delivery to the CNS was more complex and involved multiple transport systems (system y+, B0,+, y+L and b0,+) suggesting its concentration is tightly regulated.  System y+ and system y+L transporters could be involved in the CNS to blood efflux of ADMA that we have previously observed.  The half-saturation constant (Km) and maximal influx rate of the saturable component (Vmax) for [3H]-ADMA transport into the frontal cortex was 29.07±7.19 mM and 0.307±0.017 nmol.min-1.g-1, respectively, and into the CSF was 30.59±25.41 μM and 2.07±0.38 nmol.min-1.g-1, respectively.  This information could help explain the arginine paradox providing evidence that ADMA interacts with transporters that can remove ADMA from cells.  These removal mechanisms could be stimulated by excess arginine in the plasma resulting in increased NO production.  It remains to be seen if arginine supplementation could be used to increase NO production and improve hypoperfusion observed in disease states such as Alzheimer’s and stroke.
Validation of Accelerometry Cut-off Points to Categorize Physical Activity Intensity Along the Pregnancy
Authors: Cagiao A. , Fariñas J. , Rial-Vázquez J. , Rúa-Alonso M. , Díaz Brage P.A. , Giráldez M. A. , Carnero E.A.
Published: February 2025

Background

Several studies have created and validated accelerometry cut-off points to categorize intensities of physical activity (PA); however, there is not specific cut-off points in pregnant women. Pregnancy promotes specific physiological and biomechanical changes that can modify quantitively the relationship between movement and energy expenditure. The aim of this study was to develop and validate specific accelerometry cut-off points for light and moderate-vigorous PA (LPA and MVPA respectively), at each trimester of pregnancy.

Methodology

31 healthy pregnant women completed the same cardiopulmonary submaximal exercise test, at each trimester of their pregnancies. Indirect calorimetry variables and accelerometry data were registered from no-dominant wrist and right hip placements at each measurement. Internal load variables (%VO2max, %VO2R, %HR max, %HRR and METs) were used as reference for validation and ROC analyses was performed to estimate cut-off points at each trimester and location in counts/min, MIMs and EMNO units.

Results

Cut-off points obtained from the ROC analysis showed a high performance with areas under curves (AUCs) above 0.90. Cut-off points tended to be higher in no-dominant wrist than in right hip location. The cut-off for MVPA on the right hip decreased after the second trimester in ENMO and MIMS units. Only slight differences between trimesters were found in cut-off points for wrist location.

Conclusion

Accelerometer intensity cut-off points in counts, MIMS and ENMO were validated in each trimester with internal load variables for no-dominant wrist and right hip placements.
Leveraging a Vision-Language Model with Natural Text Supervision for MRI Retrieval, Captioning, Classification, and Visual Question Answering
Authors: Dhinagar Nikhil J. , Thomopoulos Sophia I. , Thompson Paul M.
Published: February 2025

Large multimodal models are now extensively used worldwide, with the most powerful ones trained on massive, general-purpose datasets. Despite their rapid deployment, concerns persist regarding the quality and domain relevance of the training data, especially in radiology, medical research, and neuroscience. Additionally, healthcare data privacy is paramount when querying models trained on medical data, as is transparency regarding service hosting and data storage. So far, most deep learning algorithms in radiologic research are designed to perform a specific task (e.g., diagnostic classification) and cannot be prompted to perform multiple tasks using natural language. In this work, we introduce a framework based on vector retrieval and contrastive learning to efficiently learn visual brain MRI concepts via natural language supervision. We show how the method learns to identify factors that affect the brain in Alzheimer’s disease (AD) via joint embedding and natural language supervision. First, we pre-train separate text and image encoders using self-supervised learning, and jointly fine-tune these encoders to develop a shared embedding space. We train our model to perform multiple tasks, including MRI retrieval, MRI captioning, and MRI classification. We show its versatility by developing a retrieval and re-ranking mechanism along with a transformer decoder for visual question answering.

Clinical Relevance

By learning a cross-modal embedding of radiologic features and text, our approach can learn to perform diagnostic and prognostic assessments in AD research as well as to assist practicing clinicians. Integrating medical imaging with clinical descriptions and text prompts, we aim to provide a general, versatile tool for detecting radiologic features described by text, offering a new approach to radiologic research.
Mechanistic Study of palmatine in Regulating Pyroptosis in Sepsis Cells via Signaling Pathways
Authors: Yan Guangzhao , Wang Yanyan
Published: February 2025

This study aims to investigate whether palmatine has a potential effect on sepsis-related pyroptosis in patients through relevant signaling pathways. Initially, the study explores the differential genes associated with pyroptosis in sepsis patients, along with their related enrichment processes, biological behaviors, and functional pathways. Patients with sepsis pyroptosis are then classified into subgroups based on pyroptosis-related genes to analyze the biological differences between these subtypes. Furthermore, the signaling pathways and biological functions associated with palmatine are studied to assess whether there are functional similarities or overlaps with the signaling pathways and biological behaviors observed in patients with sepsis pyroptosis. Finally, the findings are validated through wet-lab experiments. The results reveal that the signaling pathways related to palmatine partially overlap with those observed in sepsis pyroptosis patients, indicating that palmatine may influence sepsis pyroptosis through these pathways. Parmatine may improve the prognosis of sepsis by affecting the immune function of PRKACA, PTGS2, NLRP3, HSP90AA1 and PTPN22.
Comprehensive benchmarking of methods for mutation calling in circulating tumor DNA
Authors: Carrié Hanaé , Sim Ngak Leng , Wong Pui Mun , Gan Anna , Lau Yi Ting , Poon Polly , Thangaraju Saranya , Tan Iain , Yap Yoon Sim , Krishnamachari Kiran , Wong Limsoon , Skanderup Anders
Published: February 2025

Detection of somatic mutations in cell-free DNA (cfDNA) is challenging due to low variant allele frequencies and pronounced DNA degradation. Here, we present a novel approach and resource for benchmarking of somatic variant calling algorithms in cfDNA samples from cancer patients. Using longitudinally collected cfDNA samples from colorectal and breast cancer patients, we identify patient-matched samples with high and ultra-low circulating tumor DNA (ctDNA) levels. These sample pairs, preserving patient-specific germline and somatic haematopoiesis variant backgrounds, were used to generate dilution series capturing characteristics of bona-fide cfDNA samples. To benchmark the accuracy and limit of detection of 9 somatic variant calling algorithms, we used deep Whole Genome Sequencing (WGS, 150x) and ultra-deep Whole Exome Sequencing (WES, 2,000x) to construct a reference set of ∼37,000 Single Nucleotide Variants and ∼58,000 Insertions/Deletions. We tested methods under variable ctDNA levels and depth of sequencing, generating guidelines for method choice depending on use case. Using a machine learning approach, we further evaluated the potential of fine-tuning individual variant callers, revealing features that may improve accuracy in cfDNA samples. Overall, we present a new resource for benchmarking of somatic variant calling methods in cfDNA, providing insights on method choice to realize the potential of liquid biopsies in precision oncology.
TinkerHap - A Novel Read-Based Phasing Algorithm with Integrated Multi-Method Support for Enhanced Accuracy
Authors: Hartmann Uri , Shaham Eran , Nathan Dafna , Blech Ilana , Zeevi Danny
Published: February 2025

Phasing, the assignment of alleles to their respective parental chromosomes, is fundamental to studying genetic variation and identifying disease-causing variants. Traditional approaches, including statistical, pedigree-based, and read-based phasing, face challenges such as limited accuracy for rare variants, reliance on external reference panels, and constraints in regions with sparse genetic variation.

To address these limitations, we developed TinkerHap, a novel and unique phasing algorithm that integrates a read-based phaser, based on a pairwise distance-based unsupervised classification, with external phased data, such as statistical or pedigree phasing. We evaluated TinkerHap’s performance against other phasing algorithms using 1,040 parent-offspring trios from the UK Biobank (Illumina short-reads) and GIAB Ashkenazi trio (PacBio long-reads). TinkerHap’s read-based phaser alone achieved higher phasing accuracies than all other algorithms with 95.1% for short-reads (second best: 94.8%) and 97.5% for long-reads (second best: 95.5%). Its hybrid approach further enhanced short-read performance to 96.3% accuracy and was able to phase 99.5% of all heterozygous sites. TinkerHap also extended haplotype block sizes to a median of 79,449 base-pairs for long-reads (second best: 68,303 bp) and demonstrated higher accuracy for both SNPs and indels. This combination of a robust read-based algorithm and hybrid strategy makes TinkerHap a uniquely powerful tool for genomic analyses.
Sheathless elasto-inertial focusing of sub-25 nm particles in straight microchannels
Authors: Tanriverdi Selim , Cruz Javier , Habibi Shahriar , Sych Taras , Costa Martim , Mårtensson Gustaf , Görgens André , EL Andaloussi Samir , Brandt Luca , Tammisola Outi , Sezgin Erdinc , Russom Aman
Published: February 2025

Nanoscale biological particles, such as lipoproteins (10–80 nm) or extracellular vesicles (30–200 nm), play pivotal roles in health and disease, including conditions like cardiovascular disorders and cancer. Their effective analysis is crucial for applications in diagnostics, quality control, and nanomedicine development. While elasto-inertial focusing offers a powerful method to manipulate particles without external fields, achieving consistent focusing of nanoparticles (<500 nm) has remained a challenge. In this study, we experimentally demonstrate elasto-inertial focusing of nanoparticles as small as 25 nm using straight high-aspect-ratio microchannels in a sheathless flow. Systematic investigations reveal the influence of channel width, particle size, viscoelastic concentration, and flow rate on focusing behavior. Additionally, through numerical simulations and experimental validation, we provide insights into particle migration dynamics and viscoelastic forces governing nanoparticle focusing. Finally, we successfully focus biological particles, including liposomes (90–140 nm), extracellular vesicles (100 nm), and lipoproteins (10–25 nm), under optimized conditions, showcasing potential applications in medical diagnostics and targeted drug delivery. These findings mark a significant advancement toward size-based high-resolution particle separation, with implications for biomedicine and environmental sciences.
Characterization of bronchovascular-bundle mesenchymal stromal cells regulating antibody-secreting cell niche in rejecting lung allografts
Authors: Patrick McLinden A. , Ibuki Yuta , Tadokoro Kazuki , Walker Natalie M. , Lu Lu , Ke Fang , Vittal Ragini , Farver Carol F. , Welch Joshua D. , Lama Vibha N.
Published: February 2025

A transplanted lung offers a permissive milieu for local adaptive immune cell responses. Here, we characterize a transcriptionally and anatomically distinct adult lung-resident mesenchymal stromal population (MSC) that supports a pro-survival niche for antibody-secreting cells in rejecting lung allografts through a novel IL-6 trans-signaling/CXCL12 axis. By using a mouse orthotopic lung transplant model and Blimp1YFP recipients, we identify spatial localization of antibody-secreting cells (ASCs) and terminally differentiated plasma cells (PCs) along the bronchovascular bundles (BVBs). A previously described Foxf1+/Gli1+/Itga8-subset of collagen-expressing MSCs, which forms a 3-dimensional network along the bronchovascular bundles (BVB-MSCs), was found to be the major source of the PC survival factors CXCL12 and IL6. Cxcl12iCre/ERT2R26RtdTomato mice utilized as donors validated the expansion of this population in a rejecting graft and their intimate association with ASCs. CXCL12 expression was increased in allografts and Foxf1+ MSCs isolated from human CLAD patients. IL6 trans signaling/STAT3 signaling axis was shown to upregulate CXCL12 secretion in human MSCs, and Olamkicept-mediated neutralization of IL6 trans-signaling in murine RAS attenuates CXCL12 expression, intra-graft ASC population, and fibrogenesis. Our findings represent the first delineation of specialized CXCL12-expressing stromal cells in adult lungs and demonstrate their contribution to sustaining intragraft ASC niches and allograft fibrogenesis.
Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human brain organoid microphysiological systems
Authors: Tian Chunhui , Ao Zheng , Cerneckis Jonas , Cai Hongwei , Chen Lei , Niu Henyao , Takayama Kazuo , Kim Jungsu , Shi Yanhong , Gu Mingxia , Kanekiyo Takahisa , Guo Feng
Published: February 2025

Increasing evidence suggests that Alzheimer’s disease (AD) pathogenesis strongly correlates with neuroinflammation. Peripheral monocytes are crucial components of the human immune system that may play a role in neuroinflammation, but their contribution to AD pathogenesis is largely understudied partially due to the lack of appropriate human models. Here, we present human cortical organoid microphysiological systems (hCO-MPSs) for modeling dynamic AD neuroinflammation mediated by monocytes. By incorporating 3D printed devices into an existing cortical organoid protocol, 96 hCO-MPSs can be established with significantly reduced necrosis and hypoxia as well as enhanced viability within a commonly used 96 well plate, and each hCO-MPS consists of a doughnut-shaped hCO and a 3D printed device per well. Using this approach, monocytes from AD patients exhibit higher infiltration, decreased amyloid-beta (Aβ) clearance, and stronger inflammatory responses compared to monocytes from age-matched control donors. Moreover, pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis were observed to be induced by AD monocytes. Furthermore, the significant increase in the expression of IL1B and CCL3, both at the transcriptional and protein levels, indicated the pivotal role of these cytokine and chemokine in monocyte-mediated AD neuroinflammation. Our findings provide insight for understanding monocytes’ role in AD pathogenesis, and the user-friendly MPS models we present are compatible with existing laboratory settings, highlighting their potential for modeling neuroinflammation and developing new therapeutics for various neuroinflammatory diseases.
Genome restructuring and lineage diversification ofCryptococcus neoformansduring chronic infection of human hosts
Authors: Montoya Marhiah C. , Wilhoit Kayla , Murray Debra , Perfect John R. , Magwene Paul M.
Published: February 2025

Classified as a critical public health threat by the World Health Organization,Cryptococcus neo-formansinfections with significant morbidity and mortality. Reports of cryptococcosis persistence, relapse, and reinfection date back to the 1950s, yet the factors driving chronic infections remain poorly understood. A major challenge is the scarcity of serial patient specimens and detailed medical records to study the simultaneous evolution of the pathogen and host health status. This study provides the first genomic and phenotypic analysis of in-host evolution ofC. neoformansduring chronic infections lasting over a year in six immunocompromised patients. We find fungal genome evolution during persistent infection is characterized by large-scale genome restructuring and increasing genomic heterogeneity. Phenotypic changes show diversification in virulence traits and antifungal susceptibility. Genotypically and phenotypically distinct sub-lineages arise and co-persist within the same tissues, consistent with a model of diversifying selection and niche partitioning in the complex environment of human hosts.
Distinct Cytokine and Cytokine Receptor Expression Patterns Characterize Different Forms of Myositis
Authors: Kirou Raphael A. , Pinal-Fernandez Iago , Casal-Dominguez Maria , Pak Katherine , Preusse Corinna , Dari Dilbe , Del Orso Stefania , Naz Faiza , Islam Shamima , Gutierrez-Cruz Gustavo , Naddaf Elie , Liewluck Teerin , Stenzel Werner , Selva-O’Callaghan Albert , Milisenda Jose C. , Mammen Andrew L.
Published: February 2025

Objective

Myositis is a heterogeneous family of inflammatory myopathies. We sought to define the differential expression of cytokines, cytokine receptors, and immune checkpoint genes in muscle biopsies from patients with different forms of myositis in order to characterize patterns of inflammation in each.

Methods

Bulk RNA sequencing was performed on muscle biopsy samples from 669 patients, including 105 with dermatomyositis, 80 with immune-mediated necrotizing myopathy (IMNM), 65 with anti-synthetase syndrome, 53 with inclusion body myositis (IBM), 19 with anti-PM/Scl myositis, 310 with other inflammatory or genetic myopathies, and 37 controls with normal tissue (NT). Myositis clinical groups and autoantibody subgroups were analyzed separately. Expression data was analyzed for 338 genes encoding cytokines, cytokine receptors, and immune checkpoints. Myositis group-specific genes were identified from this list by finding genes that were specifically differentially expressed in one group compared to all samples and compared to NT (α<0.001).

Results

IBM patients had the most differentially overexpressed genes (71) among all clinical groups, including 37 that were IBM-specific. Among the top genes were several involved in type 1 inflammation, includingCCL5,CXCR3,CCR5,CXCL9, andIFNG. Anti-Jo1 and anti-PM/Scl patients exhibited differential overexpression of a similar set of genes, while dermatomyositis patients exhibited differential overexpression of a different set of genes involved in type 1 inflammation. IMNM patients had the least number of differentially overexpressed genes with no predominant inflammatory pattern.

Conclusion

Each myositis clinical group and autoantibody subgroup had differentially overexpressed inflammatory mediators, including a strong type 1 inflammatory gene signature in IBM.

Key Messages

Inclusion Body Myositis (IBM) muscle biopsies exhibit differential overexpression of a set of genes involved in type 1 inflammation.

TheCCL5-CCR5andXCL1-XCL2-XCR1axes are specifically differentially overexpressed in IBM muscle and may contribute to TC1-mediated inflammation.

Dermatomyositis, anti-Jo1 myositis, and anti-PM/Scl myositis muscle biopsies also exhibit overexpression of type 1 inflammatory genes, but to a lesser extent than IBM.
Exploring how an e-cigarette intervention influenced tobacco smoking behaviour in people accessing homelessness services: findings from the SCeTCH trial process evaluation
Authors: Ford Allison , McMillan Lauren , Cox Sharon , Soar Kirstie , Pesola Francesca , Notley Caitlin , Brown Rachel , Ward Emma , Gardner Bethany , Varley Anna , Mair Charlotte , Lennon Jessica , Brierley Janine , Edwards Amy , Micthell Danielle , Robson Debbie , Hajek Peter , Tyler Allan , Parrott Steve , Li Jinshuo , Bauld Linda , Dawkins Lynne
Published: February 2025

Background

Smoking prevalence among people experiencing homelessness is high. This study explored the factors which influenced potential smoking abstinence among participants receiving an e-cigarette (EC) intervention within the Smoking Cessation Trial in Centres for Homelessness (SCeTCH) across Great Britian.

Methods

Using the Capability Opportunity Motivation – Behaviour (COM-B) model, hypothesised and emerging mediators were explored quantitatively via measures in baseline and follow-up questionnaires (n=239) and qualitatively via interviews with homelessness centre staff (n=16) and participants (n=31) who received an EC starter pack and 4-week e-liquid supply. We purposively sampled 8 centres for interviews, representing varied regions and participant vaping/smoking and sociodemographic status. Quantitative measures were analysed descriptively. Qualitative data were analysed thematically. Data from the two approaches were mapped onto the COM-B for combined analysis and reporting.

Results

After receiving the intervention, participants demonstrated high capability to use EC and appreciation of EC for harm reduction. Some participants reported dissatisfaction with vaping. Opportunity for behaviour change was strengthened by perceived acceptability to vape and social support beyond the centre but hindered by a smoking culture and perceived lack of staff support. Motivation was enhanced by EC efficacy belief, pride from cutting down, and financial benefits of vaping, but negatively impacted by challenging personal circumstances.

Conclusion

For people accessing homelessness support centres, smoking abstinence remains challenging. More intensive support and a variety of approaches to support smoking cessation, particularly those which address the psychosocial factors which hinder smoking abstinence, may be required. Future research should focus on how this can be achieved.
Long-term memory formation impacts dietary energy intake but not metabolic rate in honeybees
Authors: Watrobska Cecylia M. , Codd Jonathan , Portugal Steven J. , Leadbeater Ellouise
Published: February 2025

The brain is energetically expensive. Energy availability may, therefore, determine whether costly cognitive processes such as long-term memory can be expressed. However, there is a limited understanding of the metabolic costs associated with long-term memory formation. Here, we explored the potential induced costs of long-term memory formation using honeybees (Apis mellifera) as a model species. We monitored the sucrose intake of bees over the 20-hour period following a classical spaced olfactory conditioning protocol that induced long-term memory formation, relative to a control group that experienced the same reward schedule but no odour pairing. Bees in the experimental treatment drank significantly more sucrose than controls. We then tested whether the increased energy demands of long-term memory formation showed parallel increases in metabolic rate, by measuring carbon dioxide production in groups of bees at four timepoints following conditioning (1-hour, 4-hours, 24-hours and 72-hours). We found no change in metabolic rate between learning and control groups across all time points. Our results suggest that the cost of long-term memory formation does not translate to increases in metabolic rate, despite an increase in dietary energy intake. Constraints on the expression of cognitive traits may, therefore, be unlikely when energy is unrestricted and can be compensated.
Direct mechanical communication of cellular to nuclear shape in oocytes
Authors: Vos Bart E. , Vadapalli Yamini , Muenker Till , Jentoft Ida Marie Astad , Todisco Elena , Eskandari Mohammad Amin , Schuh Melina , Lenart Peter , Betz Timo
Published: February 2025

The mechanical properties of the cytoplasm and nucleoplasm are crucial for the correct and robust functioning of a cell and play a key role in understanding how mechanical signals are transferred to the nucleus. Here, we demonstrate remarkable shape mimicry between the cellular and nuclear shape of oocytes, following the externally applied deformation without direct contact between the cell cortex and the nucleus. This effect arises from a surprisingly soft and fluid-like nucleoplasm that is barely resisting any external strain, while the viscoelastic cytoplasm drives shape transmission. Comparative studies in jellyfish, starfish, and mouse oocytes reveal that lower cytoplasmic elasticity in jellyfish leads to reduced nuclear shape mimicry, highlighting the role of cytoplasmic mechanics in nuclear deformation.

Significance Statement

Mechanosensing of the nucleus is, in addition to chemical signalling, an important factor in gene expression. Although nuclei are often thought to be rigid inclusions in the cytoplasm of a cell, we show that in oocytes nuclei are much more deformable. Using a combination of intranuclear, intracellular and extracellular measurements, we attribute our findings to a fine balance between the soft nucleoplasm surrounded by an elastic shell and the viscoelastic properties of the cytoplasm.
RNA Knowledge-Graph analysis through homogeneous embedding methods
Authors: Torgano Francesco , Gomez Mauricio Soto , Zignani Matteo , Gliozzo Jessica , Cavalleri Emanuele , Mesiti Marco , Casiraghi Elena , Valentini Giorgio
Published: February 2025

Motivation

We recently introduced RNA-KG, an ontology-based knowledge graph that integrates biological data on RNAs from over 60 public databases. RNA-KG captures functional relationships and interactions between RNA molecules and other biomolecules, chemicals, and biomedical concepts such as diseases and phenotypes, all represented within graph-structured bio-ontologies. We present the first comprehensive computational analysis of RNA-KG, evaluating the potential of graph representation learning and machine learning models to predict node types and edges within the graph.

Results

We performed node classification experiments to predict up to 81 distinct node types, and performed both generic and specific edge prediction tasks. Generic edge prediction focused on identifying the presence of an edge irrespective of its type, while specific edge prediction targeted specific interactions between ncRNAs, e.g. miRNA-miRNA or siRNA-mRNA, or relationships between ncRNA and biomedical concepts, e.g. miRNA-disease or lncRNA-Gene Ontology term relationships. Using embedding methods for homogeneous graphs, such as LINE and node2vec, in combination with machine learning models like decision trees and random forests, we achieved balanced accuracy exceeding 90% for the 20 most common node types and over 80% for most specific edge prediction tasks. These results show that simple embedding methods for homogeneous graphs can successfully predict nodes and edges of the RNA-KG, paving the way to discover novel ncRNA interactions and laying the foundation for further exploration and utilization of this rich information source to enhance prediction accuracy and support further research into the “RNA world”.

Code Availability

Python code to reproduce the experiments is available athttps://github.com/AnacletoLAB/RNA-KG_homogeneous_emb_analysis
diffONT: predicting methylation-specific PCR biomarkers based on nanopore sequencing data for clinical application
Authors: Meyer Daria , Barth Emanuel , Wiehle Laura , Marz Manja
Published: February 2025

DNA methylation is known to act as biomarker applicable for clinical diagnostics, especially in cancer detection. Methylation-specific PCR (MSP) is a widely used approach to screen patient samples fast and efficiently for differential methylation. During MSP, methylated regions are selectively amplified with specific primers. With nanopore sequencing, knowledge about DNA methylation is generated during direct DNA sequencing, without any need for pretreatment of the DNA. Multiple methods, mainly developed for whole-genome bisulfite sequencing (WGBS) data, exist to predict differentially methylated regions (DMRs) in the genome. However, the predicted DMRs are often very large, and not sufficiently discriminating to generate meaningful results in MSP creating a gap between theoretical cancer marker research and practical application, as no tool currently provides methylation difference predictions tailored for PCR-based diagnostics. Here we presentdiffONT, which predicts differentially methylated primer regions, directly suitable for MSP primer design and thus allowing a direct translation into practical approaches.diffONTtakes into account (i) the specific length of primer and amplicon regions, (ii) the fact that one condition should be unmethylated, and (iii) a minimal required amount of differentially methylated cytosines within the primer regions. Based on two nanopore sequencing data sets we compared the results ofdiffONTtometilene,DSSandpycoMeth. We show that the regions predicted bydiffONTare more specific towards hypermethylated regions and more usable for MSP.diffONTaccelerates the design of methylation-specific diagnostic assays, bridging the gap between theoretical research and clinical application.
Parallel adaptation to geothermally-warmed habitats due to common structural variation and functional developmental pathways
Authors: Brachmann Matthew K. , Costa Ana P. B. , Robertson Shaun , Donoghue Kate , Pilakouta Natalie , Whitehead Mark , Liu Xuan , Kristjansson Bjarni , Skulason Skuli , Selman Colin , Parsons Kevin
Published: February 2025

Climate change is causing rapid increases in temperature which drives genomic changes tied to adaptation. However, predicting the outcomes of climate change presents challenges as the anticipated conditions have yet to be experienced by natural populations. Modelling and lab experiments suggest that natural populations will experience shifts in life history, physiology, phenology, and ecology, but the underlying genomic mechanisms involved are unknown. However, some contemporary natural populations experience habitat warming through geothermal activity and can provide valuable insights into evolutionary responses. Geothermally warmed habitats should impose strong selection on ectotherms compared to ambient habitats as they increase metabolic demands, alter developmental processes, and offer novel ecological conditions. We leveraged Icelandic threespine sticklebacks (Gasterosteus aculeatus) from populations that have adaptively diverged along a geothermal/ambient habitat axis. We obtained 173,485 single nucleotide polymorphisms (SNPs) across four independent instances of population divergence using whole genome sequencing. While the majority of genomic differentiation between geothermal/ambient ecotypes was non-parallel, the MAPK signalling pathway appeared across all ecotype pairs. We also identified a putative inversion located on chromosome XXI which appears to drive parallel genomic differentiation between geothermal and ambient ecotypes. Candidate genes within the putative inversion correspond to metabolic adaptations, including regulation of appetite and fat content. Appetite level showed strong heritable divergence between ecotypes, while the rate of weight loss during starvation and fat levels differed between ecotypes. Overall, both polygenic adaptation and parallel structural variation appeared to be key genomic mechanisms for adaptation to geothermally warmed environments. While allelic divergence was largely unique across populations, it resulted in similar functional phenotypic outcomes. Thus, structural and allelic variation both operate to facilitate adaptation to warming environments. Therefore, while management from a genomic perspective will play a role in mitigating the effects of climate change, this study suggests that consideration of functional molecular pathways will be key to conservation but with precise changes being difficult to predict due to the highly polygenic nature of thermal adaptation.
Effects of a Sequential Application of Plant Protection Products on Soil Microbes and Free-Living Nematodes in a Field Experiment
Authors: Drocco Camilla , Fernandes Saúl , Xie Liyan , Devers Marion , Förster Bernhard , Martin-Laurent Fabrice , Romdhane Sana , Spor Aymé , Thiour-Mauprivez Clémence , Coors Anja
Published: February 2025

During crop growth cycle, often several different plant protection products (PPPs) are applied, in combination or sequentially. Such sequential applications result in unintentional mixtures of residues that may affect ecosystem services supported by non-target organisms such as soil microbes and nematodes. This scenario of sequential PPP application is frequent in agricultural practice but rarely addressed experimentally at field scale with regard to environmental impacts. The objective of this study was to evaluate the effect of individual and sequential application of three PPPs (the herbicide clopyralid, the insecticide zeta-cypermethrin, and the fungicide pyraclostrobin) on soil microbial communities, and on the abundance of free-living nematode. Single applications (at 1× or 10× the agronomical dose) were made to triplicated field plots with each one of the PPPs or all three PPPs in sequence, with untreated plots serving as controls. Plots were sampled prior to each application, and 7 and 28 days thereafter. The fungal community’s composition and abundance were found to be more susceptible than the bacterial community to PPP applications, while the bacterial was mainly driven by the in-field heterogeneity of soil properties. Transient effects of PPP applications were detected on nematode abundance. Higher tier ecotoxicological studies offer greater ecological relevance compared to the standard laboratory tests but are challenged by environmental variations that should be accounted for when evaluating the ecotoxicity of pesticides on soil organisms.
Transcriptome analysis of the winter tick (Dermacentor albipictus) reveals sex-specific expression patterns
Authors: Edwards Rhodri T.M. , Antoshechkin Igor , Hill Eddie , Perry Michael W. , Olafson Pia U. , Saelao Perot , Lohmeyer Kimberly H. , Akbari Omar S.
Published: February 2025

The winter tick,Dermacentor albipictus, is a significant ectoparasite of ruminants across North America, posing health risks to wildlife and occasionally humans. Despite its ecological importance, limited genomic resources exist for this species. This study provides the first comprehensive transcriptome analysis ofD. albipictus, focusing on early-stage embryos, sexed adults, dissected ovaries, and dissected male reproductive systems. Differential gene expression analyses revealed significant sex-biased expression patterns, and functional annotations identified candidate genes involved in sex determination. Notably, we identified the first documented case of sex-specific splicing of a doublesex-like gene in chelicerates, a mechanism previously thought to be absent in this group. This discovery suggests that ticks may share more insect-like features of sexual differentiation, with implications for understanding the evolution of sex determination pathways in arthropods These transcriptome data serve as a critical resource for understanding the biology ofD. albipictusand will facilitate the development of novel genetic control strategies.
Calcineurin controls the cytokinesis machinery during thermal stress inCryptococcus deneoformans
Authors: Yadav Vikas , Averette Anna Floyd , Upadhya Rajendra , Heitman Joseph
Published: February 2025

Calcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, post-transcriptional, and post-translational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a regulatory B subunit. Through downstream effectors, calcineurin signaling drives myriad responses in different organisms. In the fungal pathogenicCryptococcusspecies complex that infects humans, calcineurin governs thermotolerance and is essential for growth at high temperature and pathogenesis. InCryptococcus deneoformans, the underlying molecular functions of this critical signaling cascade are not well understood. In this study, we conducted a genetic screen and identified genetic changes that suppress the requirement for calcineurin during high-temperature growth. Our results identified two mechanisms that bypass the requirement for calcineurin function. The first mechanism involves segmental aneuploidy via both amplification as well as loss of chromosome fragments. The second mechanism involves dominant amino acid substitution mutations in the genes encoding three proteins, Chs6, Imp2, and Cts1, which function in a complex required for septation and budding. Loss of calcineurin activity causes chitin and chitosan accumulation and severe budding defects, whereas suppressor mutations restore largely normal growth and cytokinesis in the absence of calcineurin. These findings reveal the calcineurin signaling cascade controls a conserved cytokinesis machinery at the mitotic exit network during thermal stress.