bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of protein transporter function using Raman spectroscopy
Authors: Gilchrist Dominic , Islam Meez , Akram Muhammad Safwan , Dean Paul
Published: February 2025

Graphical Abstract

A summary of the workflow for identifying the function of a protein transporter using Raman spectroscopy. A putative transporter gene (ThNTT4) is cloned into a suitable expression vector [] and transformed into a heterologous expression system []. Protein expression is induced [] and confirmed [], followed by an uptake assay using alkyne-labelled substrates such as N6pATP []. Following washing and lysis of the heterologous host cell [], the lysate is spotted onto a steel slide, dried down and analysed with the Raman microscope.
Cancer cells suppress NK activity by actin-driven polarisation of inhibitory ligands at the synapse
Authors: Hoffmann Céline , Filali Liza , Wurzer Hannah , Fernandes Diogo Pereira , Mgrditchian Takouhie , Moreau Flora , Krecké Max , Thomas Clément
Published: February 2025

Natural killer (NK) cells engage target cells via the immunological synapse, where inhibitory and activating signals determine whether NK cell cytotoxicity is suppressed or activated. We report that cancer cells can rapidly remodel their actin cytoskeleton upon NK cell engagement, leading to F-actin accumulation at the synapse. This process inhibits NK cell activation as indicated by impaired MTOC and lytic granule polarization. Exploring the underlying mechanism, we found that actin remodelling drives the recruitment of inhibitory ligands, such as HLA-A, -B, and -C, to the synapse. Disrupting HLA interaction with their cognate inhibitory receptors KIRs restored NK cell activation. Using NK cells expressing inhibitory KIR receptors, matched or unmatched to HLA molecules on cancer cells, we show that synaptic F-actin accumulation and matching KIR-HLA interactions jointly suppress NK cell cytotoxicity. Our findings reveal a novel immune evasion strategy in which cancer cells impair NK cell activation by altering synaptic signalling through actin cytoskeleton-driven recruitment of inhibitory signals to the immunological synapse.
Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders
Authors: Goodman Alexander C. , Michel Kylie M. , MacBeth Morgan L. , Turner Jaqueline A. , Tobin Richard P. , Robinson William A. , Couts Kasey L.
Published: February 2025

Objectives

This study investigates the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response.

Methods

In a retrospective cohort study, serum samples from 43 stage III and stage IV melanoma patients treated at the University of Colorado Hospital from 2010 to 2023 were analyzed via ultra-high-pressure liquid chromatography-mass spectrometry. Melanoma patients were treated anti-PD-1 monotherapy or combination immune checkpoint inhibitor therapy and response was assessed using RECIST 1.1 criteria.

Results

Using mass spectroscopy, we determined global oxylipin metabolite profiles are largely uniform pre-and post-treatment across melanoma subtypes including cutaneous, acral, mucosal, and uveal melanoma. Across subtypes, 33 oxylipin metabolites were analyzed, with limited variation observed overall. Prostaglandin J2was more abundant in rare melanoma subtypes including acral, mucosal, and uveal melanoma compared to cutaneous melanoma.

Conclusions

Despite limited variation of serum oxylipin molecular species by subtype and response status, we observed significant differences in Prostaglandin J2which could serve as a potential biomarker for immune checkpoint inhibitor therapy response in melanoma. However, further investigation is warranted to explore the role of oxylipins in immune response modulation.
Strategies for Mitigating Radiation Damage and Improving Data Completeness in 3D Electron Diffraction of Protein Crystals
Authors: Shaikhqasem Alaa , Hamdi Farzad , Machner Lisa , Parthier Christoph , Breithaupt Constanze , Kyrilis Fotis L. , Feller Stephan M. , Kastritis Panagiotis L. , Stubbs Milton T.
Published: February 2025

While 3D electron diffraction (3D-ED or microcrystal electron diffraction, MicroED) has emerged as a promising method for protein structure determination, its applicability is hindered by high susceptibility to radiation damage, leading to decreasing signal-to-noise ratio in consecutive diffraction patterns that limits the quality (resolution and redundancy) of the data. In addition, data completeness may be restricted due to the geometrical limitations of current sample holders and stages. In this work, we introduce an approach that addresses these issues using a commonly available 200keV cryo-electron microscope. The multi-position acquisition technique we present here combines (a) multiple data acquisitions from a single crystal over several tilt ranges and (b) merging data from a small number of crystals, each tilted about a different axis. The robustness of this approach is demonstrated by thede novoelucidation of a protein-peptide complex structure from only two orthorhombic microcrystals.
Spatial biomarkers of response to neoadjuvant therapy in muscle-invasive bladder cancer: the DUTRENEO trial
Authors: Grande Enrique , Sibai Mustafa , Andrada Elena , Grases Daniela , Reig Oscar , Escobosa Marc , Azueta Ainara , Castellano Daniel , Puente Javier , Villarreal Jaime Martínez de , Font Albert , Alonso-Gordoa Teresa , Benítez Raquel , Moreno-Oya Ane , Álvarez-Maestro Mario , Burgos Javier , Climent M. Angel , Domínguez Mario , Galván Patricia , Galante Isabel , García Juan F. , Perez Elena , Muro Xavier García del , Guerrero-Ramos Félix , Marqués Miriam , Maroto Pablo , Paramio Jesús M. , Pinto Alvaro , Prat Aleix , Malats Núria , Durán Ignacio , Porta-Pardo Eduard , Real Francisco X.
Published: February 2025

Many studies have reported biomarkers predictive of response to immune checkpoint inhibitors (ICI) based on retrospective analyses. However, few clinical trials have tested their value prospectively. The DUTRENEO trial (EudraCT: 2017-002246-6) investigated whether an 18-gene Tumour Inflammation Signature (TIS) that can robustly identify patients who respond to ICI in multiple tumour types could stratify patients with localized muscle-invasive bladder cancer (MIBC) to receive neoadjuvant ICI (durvalumab+tremelimumab) or standard cisplatin-based neoadjuvant chemotherapy (NAC). Patients with TIS-high tumors were randomized to ICI or NAC, while patients with TIS-low tumors received NAC. A total of 73 patients were treated. Pathological complete response (pCR) rates were 38.5% (TIS-High, ICI), 30% (TIS-High, NAC), and 55% (TIS-Low, NAC) (p = 0.349), indicating that - as applied - the TIS score did not significantly enrich in responders to ICI. Post-hoc analysis showed that higher TIS thresholds improved prediction of response to ICI but excluded many responders. Multi-omics analyses of pre-treatment samples, including whole-exome sequencing, bulk RNA sequencing, and spatial transcriptomics (Visium, Xenium), revealed that bulk RNA response signatures originated mainly from cancer cells. Spatial transcriptomics showed that ICI response was associated with proximity between cancer cells and adaptive immune cells, while resistance to NAC was linked to phenotypic plasticity of cancer cells despite low genetic diversity. The unique design of the DUTRENEO trial underscores the challenges of translating retrospective biomarkers into clinical practice and highlights the importance of spatial features in understanding tumour-immune interactions. These findings suggest that integrating spatial and multi-modal biomarkers in well-designed clinical trials could improve stratification and response prediction to select neoadjuvant therapy.
Real-world experience on the use of nivolumab monotherapy for advanced renal cell carcinoma: a multicenter retrospective cohort study in Spain
Authors: Fernández-Díaz Natalia , Mateos-González María , Pertejo-Fernández Ana , Cacho-Lavín Juan Diego , Juan-Fita María José , Chirivella-González Isabel , Arruti-Ibarbia Mikel , Fernández-Calvo Ovidio , Fernández-Núñez Natalia , Méndez-Vidal María José , Lázaro-Quintela Martín , Molina-Díaz Aurea , Del Pozo-Alonso Nieves , Etxaniz-Ulazia Olatz , García-Acuña Silvia Margarita , Betancor Yoel Z. , Azueta-Etxebarria Ainara , Calatrava-Fons Ana , Lombardía-Rodríguez Helena , Alarcón-Molero Lorena , Etxegarai-Ganboa Leire , Antón-Cameselle Abraham , Bello-Giz José Antonio , Neira-De Paz Carlos Manuel , Cabaleiro Teresa , González-Serrano Teresa , Ortiz-Rey José Antonio , Sacristán-Lista Felipe , García-Rubín Silvia , Ortega Elisa , Carrato-Moñino Cristina , Aguín-Losada Santiago , León-Mateos Luis , García-González Jorge , Pinto-Marín Álvaro , Duran Ignacio , López-López Rafael , Anido-Herranz Urbano , Ruiz-Bañobre Juan
Published: February 2025

The safety and efficacy of nivolumab in treating advanced renal cell carcinoma (aRCC) patients have been evaluated in real-world evidence (RWE) studies across various European countries, but no such data from Spain have been reported until now. We conducted a multicenter, retrospective study on 222 previously treated aRCC patients to assess the efficacy of nivolumab and the impact of pre-treatment factors on therapy outcomes in a real-world clinical practice scenario in Spain. Our results were then compared with other significant clinical experiences involving aRCC patients treated with nivolumab monotherapy. With a median follow-up of 14.6 months, the median overall survival (OS) was 18.1 months (95% confidence interval [CI], 14.2-23.7 months), and the median progression-free survival (PFS) was 4.96 months (95% CI, 3.98-7.13 months). The disease control rate was 51% (95% CI, 45-58%) and the objective response rate 23% (95% CI, 18-30%). Poor IMDC risk score was independently associated with worse OS, while prior nephrectomy with better OS. Poor IMDC risk score and ≥3 metastatic sites were independently associated with worse PFS; ≥3 metastatic sites was also associated with lower disease control. Consistent with prior clinical trials and RWE studies, this research confirms the efficacy and safety of nivolumab in daily clinical practice for a cohort of unselected previously treated aRCC patients in Spain.
Assessing sustainable and healthy diets in large-scale surveys: validity and applicability of a dietary index based on a brief food group propensity questionnaire representing the EAT-Lancet planetary health diet
Authors: Miranda Agustin , Murante Anna Maria , Manca Federica , Consalez Fabio , Jani Anant , DeClerck Fabrice , Maillot Matthieu , Verger Eric
Published: February 2025

Introduction

Ensuring healthy diets within planetary boundaries is essential. However, current instruments measuring adherence to the EAT-Lancet planetary health diet are unsuitable for large-scale surveys. Simplified tools assessing consumption frequency can improve response rates, lower costs, and facilitate administration. This study aimed to develop a practical and concise index for evaluating relative adherence to the EAT-Lancet diet across large-scale multi-country surveys.

Methods

First, the EAT-Lancet Consumption Frequency Index (ELFI) was developed using a brief food propensity questionnaire of 14 food groups representing the planetary health diet from the FEAST survey, which encompassed 27 European countries (n□=□27,417). Subsequently, ELFI was further validated using 24-hour dietary recalls from the INCA3 survey (n = 1,645), correlating it with the valid EAT-Lancet Index (ELI), which evaluates absolute adherence, as well as with food group consumption, measures of nutritional health (nutrient adequacy and diet quality), and environmental impact. Analyses included assessment of reliability, structural validity, concurrent validity, and nomological validity.

Results

ELFI showed strong reliability (alpha > 0.80) and factor analysis revealed a two-factor solution: “foods to encourage” and “foods to balance and to limit”. Confirmatory factor analysis demonstrated that ELFI is structurally valid. Concurrent validity was confirmed as it was associated with sex, age, education, income, household size, physical activity and smoking habit (p < 0.05). ELFI correlated with ELI (0.44, p < 0.0001) and food group consumptions. Regarding nomological validity, the ELFI subscores for “foods to encourage” and “foods to balance and to limit” were associated with better nutritional health (β = 0.62 and 0.23, respectively; p < 0.0001) and a lower environmental impact (β = −0.16 and −0.36, respectively; p < 0.0001).

Conclusion

ELFI approach represents a valuable and easy-to-implement index for evaluating relative adherence to sustainable and healthy diets in large-scale multi-country studies.
Approaches to early intervention for common mental health problems in young people: a systematic review
Authors: Appleton Rebecca , Barnett Phoebe , Clarke Connor , Yang Jialin , Begum Sadiya , Edbrooke-Childs Julian , Emptage Isobel , Foye Una , Griffiths Jessica , Hanson Isabel , Hunt Nima Cas , Jarvis Ruby , McAuliffe Maeve , Maynard Emma , Mitchell Lizzie , Mostafa Irina , Pemovska Tamara , Saunders Rob , Trevillion Kylee , Waite Polly , Lloyd-Evans Brynmor , Johnson Sonia
Published: February 2025

Effective early support for children and young people is a high priority. Early intervention approaches for young people with psychosis or eating disorders have substantial supporting evidence, but well-established approaches to delivering a prompt, effective response to young people presenting with early symptoms of anxiety and depression are lacking. We conducted a systematic review of outcomes of early interventions or approaches for young people (between 11 and 25 years) with initial symptoms of depression, anxiety and other common mental health difficulties. Five bibliographic and two grey literature databases were searched for papers relating to youth, early intervention and common mental health problems. We conducted a narrative synthesis of models and assessed quality using CASP checklists. We included 38 studies (43 publications): of these, randomised controlled trials were high quality but other studies tended to lack control groups and be of lower quality. Approaches broadly aimed provide a more comprehensive and effective early response to symptom onset, with primary goals falling into one of: 1) Making care more comprehensive and joined up, 2) Increasing speed or ease of access to support, or 3) Providing targeted support for specific needs in addition to anxiety and depression. Some evidence indicates that these approaches may facilitate access and reduce waiting times in the short-term, whilst decreasing burden on other mental health or emergency services. Significant improvements in mental health and wellbeing compared to controls were also reported across most studies with comparator groups, alongside high acceptability. Overall, models of early intervention for depression and anxiety show promise in improving access, experience and outcomes of care for young people. However, high heterogeneity of interventions and outcomes measured limits certainty. More robust controlled studies are needed, alongside comprehensive details of support received by young people through the intervention, and evidence of what works for whom in which settings.
A preliminary attempt to harmonize using physics-constrained deep neural networks for multisite and multiscanner MRI datasets (PhyCHarm)
Authors: Lee Gawon , Ye Dong Hye , Oh Se-Hong
Published: February 2025

In magnetic resonance imaging (MRI), variations in scan parameters and scanner specifications can result in differences in image appearance. To minimize these differences, harmonization in MRI has been suggested as a crucial image processing technique. In this study, we developed an MR physics-based harmonization framework, Physics-Constrained Deep Neural Network for Multisite and multiscanner Harmonization (PhyCHarm). PhyCHarm includes two deep neural networks: (1) the Quantitative Maps Generator to generate T1- and M0-maps and (2) the Harmonization Network. We used an open dataset consisting of 3T MP2RAGE images from 50 healthy individuals for the Quantitative Maps Generator and a traveling dataset consisting of 3T T1w images from 9 healthy individuals for the Harmonization Network. PhyCHarm was evaluated using the structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), and normalized-root-mean square error (NRMSE) for the Quantitative Maps Generator, and using SSIM, PSNR, and volumetric analysis for the Harmonization network, respectively. PhyCHarm demonstrated increased SSIM and PSNR, the highest Dice score in the FSL FAST segmentation results for gray and white matter compared to U-Net, Pix2Pix, and CALAMITI. PhyCHarm showed a greater reduction in volume differences after harmonization for gray and white matter than U-Net, Pix2Pix, or CALAMITI. As an initial step toward developing advanced harmonization techniques, we investigated the applicability of physics-based constraints within a supervised training strategy. The proposed physics constraints could be integrated with unsupervised methods, paving the way for more sophisticated harmonization qualities.
EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes
Authors: Gonzalez-Lozano Miguel A. , Schmid Ernst W. , Whelan Enya Miguel , Jiang Yizhi , Paulo Joao A. , Walter Johannes C. , Harper J. Wade
Published: February 2025

Early/sorting endosomes are dynamic organelles that play key roles in proteome control by triaging plasma membrane proteins for either recycling or degradation in the lysosome1,2,3. These events are coordinated by numerous transiently-associated regulatory complexes and integral membrane components that contribute to organelle identity during endosome maturation4. While a subset of the several hundred protein components and cargoes known to associate with endosomes have been studied at the biochemical and/or structural level, interaction partners and higher order molecular assemblies for many endosomal components remain unknown. Here, we combine cross-linking and native gel mass spectrometry5-8of purified early endosomes with AlphaFold9,10and computational analysis to create a systematic human endosomal structural interactome. We present dozens of structural models for endosomal protein pairs and higher order assemblies supported by experimental cross-links from their native subcellular context, suggesting structural mechanisms for previously reported regulatory processes. Using induced neurons, we validate two candidate complexes whose interactions are supported by crosslinks and structural predictions: TMEM230 as a subunit of ATP8/11 lipid flippases11and TMEM9/9B as subunits of CLCN3/4/5 chloride-proton antiporters12. This resource and its accompanying structural network viewer provide an experimental framework for understanding organellar structural interactomes and large-scale validation of structural predictions.
A haplotype-resolved reference genome forEucalyptus grandis
Authors: Lötter Anneri , Bruna Tomas , Duong Tuan A. , Barry Kerrie , Lipzen Anna , Daum Chris , Yoshinaga Yuko , Grimwood Jane , Jenkins Jerry W. , Talag Jayson , Borevitz Justin , Lovell John T. , Schmutz Jeremy , Wegrzyn Jill L. , Myburg Alexander A.
Published: February 2025

E. grandisis a hardwood tree used worldwide as pure species or hybrid partner to breed fast-growing plantation forestry crops that serve as feedstocks of timber and lignocellulosic biomass for pulp, paper, biomaterials and biorefinery products. The current v2.0 genome reference for the species (Bartholome et al., 2015; Myburg et al., 2014) served as the first reference for the genus and has helped drive the development of molecular breeding tools for eucalypts. Using PacBio HiFi long reads and Omni-C proximity ligation sequencing, we produced an improved, haplotype phased assembly (v4.0) for TAG0014, an early-generation selection ofE. grandis.The two haplotypes are 571 Mbp (HAP1) and 552 Mbp (HAP2) in size and consist of 37 and 46 contigs scaffolded onto 11 chromosomes (contig N50 of 28.9 and 16.7 Mbp), respectively. These haplotype assemblies are 70 to 90 Mbp smaller than the diploid v2.0 assembly but capture all except one of the 22 telomeres, suggesting that substantial redundant sequence was included in the previous assembly. A total of 35,929 (HAP1) and 35,583 (HAP2) gene models were annotated, of which 438 and 472 contain long introns (>10 kbp) in gene models previously (v2.0) identified as multiple smaller genes. These and other improvements have increased gene annotation completeness levels from 93.8% to 99.4% in the v4.0 assembly. We found that 6,493 and 6,346 genes are within tandem duplicate arrays (HAP1 and HAP2, respectively, 18.4% and 17.8% of the total) and >43.8% of the haplotype assemblies consists of repeat elements. Analysis of synteny between the haplotypes and theE. grandisv2.0 reference genome revealed extensive regions of collinearity, but also some major rearrangements, and provided a preview of population and pan-genome variation in the species.

Paper summary

We assembled a haplotype-phased genome forEucalyptus grandisthat will serve as reference for the most widely planted hardwood crop globally. It includes more than 430 new gene models with long introns and has 6% higher annotation completeness. The phased assembly provides a more accurate look at genome variation at DNA and transcript level and will better support future studies of genome structure and function. The improved assembly contains more tandem duplicate genes compared to the previous unphased reference. Finally, major genomic rearrangements between the two phased genomes provide a preview of pangenome and structural variation inE. grandis.
WISER: an innovative and efficient method for correcting population structure in omics-based selection and association studies
Authors: Jacquin Laval , Guerra Walter , Lewandowski Mariusz , Patocchi Andrea , Rymenants Marijn , Durel Charles-Eric , Laurens François , Aranzana Maria José , Muranty Hélène
Published: February 2025

This work introduces WISER (whitening and successive least squares estimation refinement), an innovative and efficient method designed to enhance phenotype estimation by addressing population structure. WISER outperforms traditional methods such as least squares (LS) means and best linear unbiased prediction (BLUP) in phenotype estimation, offering a more accurate approach for omics-based selection and association studies. Unlike existing approaches which correct for population structure, WISER offers a generalized framework that can be applied across diverse experimental setups, species, and omics datasets, such as single nucleotide polymorphisms (SNPs), near-infrared spectroscopy (NIRS), and metabolomics. Within its framework, WISER extends classical methods that use eigen-information as fixed-effect covariates to correct for population structure, by relaxing their assumptions and implementing a true whitening matrix instead of a pseudo-whitening matrix. This approach corrects fixed effects (e.g., environmental effects) for the genetic covariance structure embedded within the experimental design, thereby removing confounding factors between fixed and genetic effects. To support its practical application, a user-friendly R package namedwiserhas been developed. The WISER method has been employed in analyses for genomic prediction and heritability estimation across four species and 33 traits using multiple datasets, including rice, maize, apple, and Scots pine. Results indicate that genomic predictive abilities based on WISER-estimated phenotypes consistently outperform the LS-means and BLUP approaches for phenotype estimation, regardless of the predictive model applied. This underscores WISER’s potential to advance omics analyses and related research fields by capturing stronger genetic signals.
PH-LLM: Public Health Large Language Models for Infoveillance
Authors: Zhou Xinyu , Zhou Jiaqi , Wang Chiyu , Xie Qianqian , Ding Kaize , Mao Chengsheng , Liu Yuntian , Cao Zhiyuan , Chu Huangrui , Chen Xi , Xu Hua , Larson Heidi J. , Luo Yuan
Published: February 2025

Background

The effectiveness of public health intervention, such as vaccination and social distancing, relies on public support and adherence. Social media has emerged as a critical platform for understanding and fostering public engagement with health interventions. However, the lack of real-time surveillance on public health issues leveraging social media data, particularly during public health emergencies, leads to delayed responses and suboptimal policy adjustments.

Methods

To address this gap, we developed PH-LLM (Public Health Large Language Models for Infoveillance)—a novel suite of large language models (LLMs) specifically designed for real-time public health monitoring. We curated a multilingual training corpus comprising 593,100 instruction-output pairs from 36 datasets, covering 96 public health infoveillance tasks and 6 question-answering datasets based on social media data. PH-LLM was trained using quantized low-rank adapters (QLoRA) and LoRA plus, leveraging Qwen 2.5, which supports 29 languages. The PH-LLM suite includes models of six different sizes: 0.5B, 1.5B, 3B, 7B, 14B, and 32B. To evaluate PH-LLM, we constructed a benchmark comprising 19 English and 20 multilingual public health tasks using 10 social media datasets (totaling 52,158 unseen instruction-output pairs). We compared PH-LLM’s performance against leading open-source models, including Llama-3.1-70B-Instruct, Mistral-Large-Instruct-2407, and Qwen2.5-72B-Instruct, as well as proprietary models such as GPT-4o.

Findings

Across 19 English and 20 multilingual evaluation tasks, PH-LLM consistently outperformed baseline models of similar and larger sizes, including instruction-tuned versions of Qwen2.5, Llama3.1/3.2, Mistral, and bloomz, with PH-LLM-32B achieving the state-of-the-art results. Notably, PH-LLM-14B and PH-LLM-32B surpassed Qwen2.5-72B-Instruct, Llama-3.1-70B-Instruct, Mistral-Large-Instruct-2407, and GPT-4o in both English tasks (>=56.0% vs. <= 52.3%) and multilingual tasks (>=59.6% vs. <= 59.1%). The only exception was PH-LLM-7B, with slightly suboptimal average performance (48.7%) in English tasks compared to Qwen2.5-7B-Instruct (50.7%), although it outperformed GPT-4o mini (46.9%), Mistral-Small-Instruct-2409 (45.8%), Llama-3.1-8B-Instruct (45.4%), and bloomz-7b1-mt (27.9%).

Interpretation

PH-LLM represents a significant advancement in real-time public health infoveillance, offering state-of-the-art multilingual capabilities and cost-effective solutions for monitoring public sentiment on health issues. By equipping global, national, and local public health agencies with timely insights from social media data, PH-LLM has the potential to enhance rapid response strategies, improve policy-making, and strengthen public health communication during crises and beyond.

Funding

This study is supported in part by NIH grants R01LM013337 (YL).
Multi-lineage transcriptional and cell communication signatures define pathways in individuals at-risk for developing rheumatoid arthritis that initiate and perpetuate disease
Authors: Liu Cong , Prideaux E. Barton , Wu Peiyao , Boyle David L , Westermann Amy , Nguyen Katherine , Tsaltskan Vlad , Lazaro Leander , Ochoa Andrea , Deane Kevin D. , Feser Marie L. , Demoruelle M. Kristen , Kuhn Kristine A. , Holers V. Michael , Zhang Fan , Moss Laura Kay , Criley Megan , Hattel Brian , Siedschlag Marguerite , Okada Lauren , Gillespie Mark A. , Genge Palak , Weiss Morgan , Hernandez Veronica , Reading Julian , Becker Lynne , Buckner Jane H. , Speake Cate , Bumol Thomas F. , Skene Peter , Firestein Gary S. , Wang Wei
Published: February 2025

Elevated anti-citrullinated protein antibodies (ACPA) levels in the peripheral blood are associated with an increased risk for developing rheumatoid arthritis (RA). Currently, no treatments are available that prevent progression to RA in these at-risk individuals. In addition, diverse pathogenic mechanisms underlying a common clinical phenotype in RA complicate therapy as no single agent is universally effective. We propose that a unifying set of transcription factor and their downstream pathways regulate a pro-inflammatory cell communication network, and that this network allows multiple cell types to serve as pathogenic drivers in at-risk individuals and in early RA. To test this hypothesis, we identified ACPA-positive at-risk individuals, patients with early ACPA-positive RA and matched controls. We measured single cell chromatin accessibility and transcriptomic profiles from their peripheral blood mononuclear cells. The datasets were then integrated to define key TF, as well as TF-regulated targets and pathways. A distinctive TF signature was enriched in early RA and at-risk individuals that involved key pathogenic mechanisms in RA, including SUMOylation, RUNX2, YAP1, NOTCH3, and β-Catenin Pathways. Interestingly, this signature was identified in multiple cell types, including T cells, B cells, and monocytes, and the pattern of cell type involvement varied among the at-risk and early RA participants, supporting our hypothesis. Similar patterns of individualized gene expression patterns and cell types were confirmed in single cell studies of RA synovium. Cell communication analysis revealed that the lineages displaying this RA TF signature deliver a common set of pro-inflammatory mediators to receiver cells that subsequently orchestrate rheumatoid inflammation. These cell-type-specific signature pathways could explain the personalized pathogenesis of RA and contribute to the diversity of clinical responses to targeted therapies. Furthermore, these data could provide opportunities for stratifying individuals at-risk for RA, and selecting therapies tailored for prevention or treatment of RA. Overall, this study supports a new paradigm to understand how a common clinical phenotype could arise from diverse pathogenic mechanisms and demonstrates the relevance of peripheral blood cells to synovial disease.
From citizen to scientist: evaluating ant observation accuracy on a Mediterranean archipelago
Authors: Arcos Javier
Published: February 2025

Citizen science platforms, such as iNaturalist, have become invaluable tools for biodiversity monitoring, allowing non-experts to contribute photo-based observations that are then identified by the user community. However, one of the major challenges of these platforms concerns the accuracy of these identifications, especially for taxa requiring specialized knowledge or more sophisticated means of identification. In this study, I assess the reliability of ant identifications in the Balearic Islands by comparing community-generated identifications with expert validations across multiple taxonomic levels. Based on 300 iNaturalist observations, I analyze the influence of user experience, AI-generated suggestions, image quality, and community participation on identification accuracy. The results indicate that species-level accuracy was 69.91%, increasing to 90.91% at the genus level and 99% at the family level. Experienced users significantly improved accuracy, while early-stage identifications at finer taxonomic resolutions increased the likelihood of correct consensus. AI-assisted identifications performed well for frequently recorded species but struggled with underrepresented taxa. Surprisingly, photo quality had minimal impact, as common species were often identifiable even from low-resolution images. Additionally, the dataset documented exotic species, including the first record of theFormica rufibarbiscomplex in Mallorca. These findings highlight both the strengths and limitations of citizen science in taxonomic research and emphasize the need for strategies to enhance data reliability for conservation and biodiversity monitoring.
Quiescence modulates age-related changes in the functional capacity of highly proliferative canine lung mesenchymal stromal cell populations
Authors: Agyapong Nakesha , Dominguez-Ortega Leslie , Macdonough Brian , Mulluso Patrick , Patel Sagar , Prajapati Briti , Saville Brian , Shapiro Andrew , Trim Ethan , Battaglia Kara , Herrera Jocelyn , Garifo-MacPartland Gianna , Newcombe Dianne , Okundaye Latoya , Paglia Heather , Paxson Julia
Published: February 2025

The functional capacity of highly proliferative cell populations changes with age. Here, we report that the proliferative capacity of canine lung mesenchymal stromal cells (LMSCs) declines with increasing age of the donor. However, other functional changes such as reduced autophagy, reduced migration/wound healing, increased production of reactive oxygen species, and increased senescence are not significantly altered with increasing age. Furthermore, transcriptomic profiling suggests minimal age-related changes. These data suggest that the reduced proliferative capacity of lung LMSCs isolated from aging donors may be associated with reversible cell cycle arrest (quiescence), rather than irreversible cell cycle arrest (senescence). Similar findings have been reported in other systems, including neural and muscle stem cells that are associated with low turnover-rate tissues.
Neofunctionalized RGF pathways drive haustorial organogenesis in parasitic plants
Authors: Fishman Maxwell R. , Greifenhagen Anne , Wakatake Takanori , Laohavisit Anuphon , Hiroyama Ryoko , Masuda Sachiko , Shibata Arisa , Yoshida Satoko , Shirasu Ken
Published: February 2025

Parasitic plants initiate rapidde novoorganogenesis of a specialized feeding structure called a haustorium upon contact with their hosts. Currently, little is known about the internal signals regulating haustorium development. Here, we identify root meristem growth factor (RGF) peptides inPhtheirospermum japonicumas endogenous inducers of prehaustorium formation. Treatment with specific RGF peptides in the absence of hosts triggered prehaustoria and induced expression ofPjYUC3, a gene required for auxin biosynthesis and prehaustorium formation. CRISPR-mediated knockouts showed that PjRGFR1 and PjRGFR3, receptors activated by the haustorium specific RGF peptides PjRGF2 and PjRGF5, are essential for prehaustorium formation, revealing functional redundancy. Phylogenic analyses indicate that PjRGF2 is broadly conserved among Orobanchaceae, whereas PjRGF5 appears to have recently evolved through tandem multiplication and neofunctionalization. Our findings establish RGF peptides and their corresponding receptors as critical components of haustorium developmental signaling and provide insights into the evolutionary trajectories that shape plant parasitism.

Teaser

Plant peptide hormones regulate and induce the parasitic plant specialized organ for connecting to and feeding from the host.
Continuous and widespread population interactions in the Jōmon society via geometric morphometrics on 3D data of human crania
Authors: Nakao Hisashi , Kaneda Akihiro , Tamura Kohei , Noshita Koji , Yoshida Mayu , Nakagawa Tomomi
Published: February 2025

This study examines the morphological variations within and between regional populations via geometric morphometrics of larger samples of three-dimensional data of Jōmon human crania (N= 363, including 146 females, 215 males and two unknown-sex individuals) from 97 sites to investigate the population interactions in the period, which Japanese anthropologists and archaeologists have extensively discussed. The results show that morphological variations are more pronounced within individual populations especially in the principal component one, relating to the facial width, degree of prognathism, and location of occipital areas, in contrast to the relatively smaller variations observed between different phases and geographical regions. This observation is consistent with the possibility that the population interactions of the Jōmon people had been widespread and continuous, and which has an important implication for their resilience against severe climate changes at that time: The relative stability of the Jōmon society might be sustained by their frequent interactions with various populations, as suggested by insights from relevant archaeological, ethnographic, and genetic research.
Calculation of heavy meson light-cone distribution amplitudes from lattice QCD
Authors: Han Xue-Ying , Hua Jun , Ji Xiangdong , Lü Cai-Dian , Schäfer Andreas , Su Yushan , Wang Wei , Xu Ji , Yang Yibo , Zhang Jian-Hui , Zhang Qi-An , Zhao Shuai ,   Lattice Parton Collaboration
Published: February 2025

We develop an approach for calculating heavy quark effective theory (HQET) light-cone distribution amplitudes (LCDAs) by employing a sequential effective theory methodology. The theoretical foundation of the framework is established, elucidating how the quasidistribution amplitudes (quasi-DAs) with three scales can be utilized to compute HQET LCDAs. We provide theoretical support for this approach by demonstrating the rationale behind devising a hierarchical ordering for the three involved scales, discussing the factorization at each step, clarifying the underlying reason for obtaining HQET LCDAs in the final phase, and addressing potential theoretical challenges. The lattice QCD simulation aspect is explored in detail, and the computations of quasi-DAs are presented. We employ three fitting strategies to handle contributions from excited states and extract the bare matrix elements. For renormalization purposes, we apply hybrid renormalization schemes at short and long distance separations. To mitigate long-distance perturbations, we perform an extrapolation in λ=z·Pz and assess the stability against various parameters. After two-step matching, our results for HQET LCDAs are found in agreement with existing model parametrizations. The potential phenomenological implications of the results are discussed, shedding light on how these findings could impact our understanding of the strong interaction dynamics and physics beyond the standard model. It should be noted, however, that systematic uncertainties have not been accounted for yet.

Published by the American Physical Society
2025
Quantum coherence in neutrino spin-flavor oscillations
Authors: Alok Ashutosh Kumar , Chall Trambak Jyoti , Chundawat Neetu Raj Singh , Gangal Shireen , Lambiase Gaetano
Published: February 2025

Coherence, which represents the superposition of orthogonal states, is a fundamental concept in quantum mechanics and can also be precisely defined within quantum resource theory. Thus exploring quantum coherence in neutrino oscillations can not only help in examining the intrinsic quantum nature but can also explore their potential applications in quantum information technologies. Previous studies on quantum coherence have focused on neutrino flavor oscillations (FO). However, FO imply that neutrinos have mass, and this can lead to the generation of a tiny but finite magnetic dipole moment of neutrinos through quantum loop diagrams at higher orders of perturbative expansion of the interaction. This electromagnetic property of neutrinos can induce spin flavor oscillations (SFO) in the presence of an external magnetic field and hence is expected to enrich the study of coherence. In this work, we investigate quantum coherence in neutrino SFO with three flavor mixing within the interstellar as well as intergalactic magnetic fields, quantified by the l1 norm and the relative entropy of coherence, and express these measures in terms of neutrino SFO probabilities. For FO, coherence measures can sustain higher values (say, within 50% of the maximum) over distances of several kilometers, which are relevant for terrestrial experiments like reactor and accelerator neutrinos. However, for SFO, we find that the coherence scale can extend to astrophysical distances, spanning from kiloparsecs to gigaparsecs.

Published by the American Physical Society
2025
Ripples of the QCD critical point
Authors: Fu Wei-jie , Luo Xiaofeng , Pawlowski Jan M. , Rennecke Fabian , Yin Shi
Published: February 2025

We investigate the impact of a critical end point (CEP) on the experimentally accessible baryon-number fluctuations of different orders. By now, its potential location has been constrained fairly accurately within first principles functional QCD, together with the location of the chiral crossover line and further thermodynamic observables. This information is incorporated in an advanced QCD-assisted low-energy effective theory which is used for the computation of baryon-number fluctuations at the chemical freeze-out. This computation also takes care of global baryon-number conservation at larger density, where the system changes from grand-canonical to canonical statistics. We observe a prominent peak structure, whose amplitude depends on the location of the CEP, while its position is more sensitive to the location of the freeze-out curve. Our results provide guidance for future low-energy heavy-ion experiments.

Published by the American Physical Society
2025
Propagation of two-particle correlations across the chaotic phase for interacting bosons
Authors: Dueñas Óscar , Peña David , Rodríguez Alberto
Published: February 2025

We analyze the propagation of experimentally relevant two-particle correlations for one-dimensional interacting bosons, and give evidence that many-body chaos induces the emergence of an effective diffusive regime for the fully coherent correlation dynamics, characterized by an interaction dependent diffusion coefficient, which we estimate. This result supports very recent experimental observations, and paves the way toward an efficient description of the dynamical behavior of nonintegrable complex many-body systems. Furthermore, we show that the dynamical features within experimentally accessible time scales of a conveniently defined two-particle correlation transport distance provide a direct and unambiguous characterization of many-body quantum chaos in perfect agreement with its spectral identification.

Published by the American Physical Society
2025
Exploring integration aspects of school leadership in the context of digitalization and artificial intelligence
Authors: Kafa Antonios
Published: February 2025

Purpose

The rapid digitalization and emergence of AI tools are transforming school organizations. However, limited research exists on how school leaders integrate these technologies into their leadership practices. This study focuses on the experiences of school leaders in Cyprus, exploring the benefits and challenges of adopting digital and AI tools in their roles. The research seeks to enhance understanding of these topics as they relate to the pandemic aftermath and the current emergence of cutting-edge technologies.

Design/methodology/approach

A qualitative research approach was used, with semi-structured interviews serving as the primary data collection method. The sample consisted of 43 school leaders from primary and secondary schools across five districts in Cyprus, who voluntarily participated in the study.

Findings

The findings reveal that while digital tools enhance communication and administrative efficiency, challenges associated with poor infrastructure and inadequate targeted training were disclosed. In addition, school leaders acknowledge the potential of AI to support their leadership practice, while also addressing the challenges of integrating these tools due to limited knowledge and understanding, lack of appropriate training and the need of an ongoing support.

Practical implications

The study emphasizes the need for tailored professional development, better infrastructure and continuous support to help school leaders effectively integrate digital and AI tools into their daily leadership practices.

Originality/value

This research contributes uniquely to the field by focusing on the integration of digital tools, while also exploring, to some extent, perspectives on AI within school leadership in Cyprus, in an area that has been largely underexplored.
Responsible and sustainable tourism (respo-sustainable tourism): a systematic literature review and future agenda
Authors: Dhama Neeru , Anil Kanwal
Published: February 2025

Purpose

This study aims to present a systematic literature review of the responsible and sustainable tourism and also to examine the relationship between responsible and sustainable tourism.

Design/methodology/approach

In total, 59 articles were used as a sample in this research to extract the methodological trends emanating from them. Subsequently, thematic analysis was undertaken to understand the effectiveness of responsible and sustainable tourism in the current milieu.

Findings

A detailed analysis of responsible tourism and its relation with sustainable tourism has been done, and further suggestions have been discussed to overcome the problem of mass tourism and achieve sustainability.

Originality/value

Sustainable and responsible tourism is the mandate of sustainability concerns in today’s era. This paper helps the stakeholders to perform responsible and sustainable tourism practices after understanding the concept and their relationship in the tourism industry.
Navigating paradoxical tensions in pursuit of sustainable supply chain management: review and guidance for future inquiry
Authors: Cichosz Marzenna , Aluchna Maria , Sońta-Drączkowska Ewa , Knemeyer A. Michael
Published: February 2025

Purpose

Organizational pursuit of sustainability in multi-tier supply chain systems operating in unpredictable environments is often associated with the emergence of paradoxical tensions. This study aims to summarize and synthesize existing literature on managing various paradoxical tensions in supply chains (i.e. sourcing, making, delivering and reverse logistics) as organizations pursue sustainability transformation. It also strives to motivate new academic research inquiry into developing responses to sustainability paradoxes.

Design/methodology/approach

The study draws on a systematic literature review of 73 papers from the Web of Science database selected at the intersection of paradox, sustainability and logistics/ supply chain management (SCM). Applying paradox theory as a guiding lens, we investigate organizational strategies, practices and capabilities described in the literature to navigate sustainability paradoxes in supply chains.

Findings

The results assert that the success of sustainability transformation will depend on an organizational ability to recognize, accept and navigate paradoxical tensions in one's supply chain. This requires developing the dynamic capabilities of paradoxical leadership, strategic agility, innovativeness, collaboration with contextualization and governance. Successful sustainability transformation is not reliant on finding an optimal, final design but rather the continuous balancing of tensions inherent within or across the organizations that make up one's supply chain.

Practical implications

The research offers an integrative conceptual framework to guide organizations in navigating sustainability paradoxes in supply chains, embracing strategic, practice and capability levels. It also outlines opportunities for future research inquiries connected to this framework that are needed to build additional insight for addressing paradoxical tensions related to the pursuit of sustainable supply chain management.

Originality/value

This study takes a dynamic capabilities approach to navigating paradoxical tensions in pursuit of sustainable supply chain management.