bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning model for protein multi-label subcellular localization and function prediction based on multi-task collaborative training
Authors: Bai Peihao , Li Guanghui , Luo Jiawei , Liang Cheng 
Published: November 2024

Abstract
The functional study of proteins is a critical task in modern biology, playing a pivotal role in understanding the mechanisms of pathogenesis, developing new drugs, and discovering novel drug targets. However, existing computational models for subcellular localization face significant challenges, such as reliance on known Gene Ontology (GO) annotation databases or overlooking the relationship between GO annotations and subcellular localization. To address these issues, we propose DeepMTC, an end-to-end deep learning-based multi-task collaborative training model. DeepMTC integrates the interrelationship between subcellular localization and the functional annotation of proteins, leveraging multi-task collaborative training to eliminate dependence on known GO databases. This strategy gives DeepMTC a distinct advantage in predicting newly discovered proteins without prior functional annotations. First, DeepMTC leverages pre-trained language model with high accuracy to obtain the 3D structure and sequence features of proteins. Additionally, it employs a graph transformer module to encode protein sequence features, addressing the problem of long-range dependencies in graph neural networks. Finally, DeepMTC uses a functional cross-attention mechanism to efficiently combine upstream learned functional features to perform the subcellular localization task. The experimental results demonstrate that DeepMTC outperforms state-of-the-art models in both protein function prediction and subcellular localization. Moreover, interpretability experiments revealed that DeepMTC can accurately identify the key residues and functional domains of proteins, confirming its superior performance. The code and dataset of DeepMTC are freely available at https://github.com/ghli16/DeepMTC.
Semantic Guided Matting Net
Authors: Song Qing , Sun Wenfeng , Yang Donghan , Hu Mengjie , Liu Chun 
Published: November 2024

Abstract
Human matting refers to extracting human parts from natural images with high quality, including human detail information such as hair, glasses, hats, etc. This technology plays an essential role in image synthesis and visual effects in the film industry. When the green screen is not available, the existing human matting methods need the help of additional inputs (such as trimap, background image, etc.), or the model with high computational cost and complex network structure, which brings great difficulties to the application of human matting in practice. To alleviate such problems, we use a segmentation network as the foundation and use multiple branches to achieve human segmentation, contour detail extraction, and information fusion. We also propose a foreground probability map module, which uses the feature maps in the segmentation network to pre-estimate the foreground probabilities of each pixel and obtain Semantic Guided Matting Net. Under the condition that only a single image is needed as the input, the human matting task can be realized by making full use of the semantic information in the image. We validate our method on the P3M-10k dataset. Compared with the benchmark, our method has made significant improvements in various evaluation indicators.
Effectiveness of Transitional Care in Inflammatory Bowel Disease; Development, Validation, and Initial Outcomes of a Transition Success Score
Authors: van Gaalen Martha A C , van Pieterson Merel , Waaijenberg Petra , Kindermann Angelika , Wolters Victorien M , Dijkstra Alie , van Wering Herbert , Wessels Margreet , de Ridder Lissy , Rizopoulos Dimitris , Derikx C Lauranne A A P , Escher Johanna C ,   the Kids with Crohn’s, Colitis (KiCC) Working Group for Collaborative Paediatric IBD Research in the Netherlands, the Dutch Initiative on Crohn and Colitis (ICC) and Dutch Nurses Network Inflammatory Bowel Disease (NIBD), van Rheenen Patrick F , Teklenburg Sarah T A , van Schaik Fiona D M , van der Woude Janneke C , Hoekstra Jildou , de Leest Marleen , Bakker Carla , Besuijen-Laterveer Elvira M E , Adriaanse Esther , Wisse Jolien , Heida Marloes , Hurkmans Pamela , Boontje Nynke , Toonen Tessa Z , Heida Wendy 
Published: November 2024

Abstract

Background and Aims
The effectiveness of transition programs from pediatric to adult healthcare in adolescents with inflammatory bowel disease (IBD) is not clear, as prospective studies using validated outcome measures for transition are lacking. This study aimed to develop and validate a quantitative Transition Success Score (TSS), and to apply it in a multicenter setting to assess the effectiveness of transitional care.

Methods
The Top 10 outcome items related to a successful transition, identified through an international Delphi study with IBD stakeholders, were integrated into a generic questionnaire, the TSS. In a prospective, multicenter study, the TSS was scored by adult healthcare providers, young adult patients, and caregivers, 9-15 months after transfer of care.

Results
In 7 Dutch hospitals, 160 patients completed the TSS. The mean score was 25 (range 17-27), 25.6% of patients achieving maximum score. Hypothesis testing for construct validity revealed significant associations with characteristics related to transitional care, such as knowledge, independence, and quality of life (p &lt; 0.005). Structural validation indicated the score was most effective at discerning lower levels of transition success. Internal consistency was acceptable (0.64). High disease burden, exacerbation during or after transfer, and certain personality profiles were associated with lower scores.

Conclusions
The TSS serves as a quantitative tool to evaluate the effectiveness of transitional care interventions and to identify IBD patients at risk of encountering challenges during the transition to adult healthcare.
Vascular and inflammatory biomarkers of cardiovascular events in non-steroidal anti-inflammatory drug users
Authors: Vaja Ricky , Ferreira Plinio , Portas Laura , Ahmetaj-Shala Blerina , Cypaite Neringa , Gashaw Hime , Quint Jennifer , Khamis Ramzi , Hartley Adam , MacDonald Thomas M , Mackenzie Isla S , Kirkby Nicholas S , Mitchell Jane A 
Published: November 2024

Abstract

Aims
The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular and renal dysfunction in NSAID cardiovascular toxicity, our understanding of these mechanisms remains incomplete. A post hoc analysis of the SCOT cohort was performed to identify clinical risk factors and circulating biomarkers of cardiovascular events in NSAID users.

Methods and results
Within SCOT (7295 NSAID users with osteoarthritis or rheumatoid arthritis), clinical risk factors associated with cardiovascular events were identified using least absolute shrinkage and selection operator regression. A nested case–control study of serum biomarkers including targeted proteomics was performed in individuals who experienced a cardiovascular event within 1 year (n = 49), matched 2:1 with controls who did not (n = 97). Risk factors significantly associated with cardiovascular events included increasing age, male sex, smoking, total cholesterol:HDL ratio ≥5, and aspirin use. Statin use was cardioprotective [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.46–0.98]. There was significantly higher immunoglobulin (Ig)G anti-malondialdehyde-modified LDL (MDA-LDL), asymmetric dimethylarginine (ADMA), and lower arginine/ADMA. Targeted proteomic analysis identified serum growth differentiation factor 15 (GDF-15) as a candidate biomarker [area under the curve of 0.715 (95% CI 0.63–0.81)].

Conclusion
Growth differentiation factor 15 has been identified as a candidate biomarker and should be explored for its mechanistic contribution to NSAID cardiovascular toxicity, particularly given the remarkable providence that GDF-15 was originally described as NSAID-activated gene-1.
Digest: Scarce pollen resources and asymmetric reproductive isolation
Authors: Gross Karin 
Published: November 2024

Abstract
What mechanisms cause asymmetries in reproductive success in crosses between closely related species that differ in floral style length? Feller et al. (2024) found that in 5 Phlox species, short-styled species produced smaller pollen grains than long-styled species. The smaller pollen of short-styled species lacked the resources to grow pollen tubes long enough to reach the ovules of long-styled species. This asymmetric pollen-style-length incompatibility may considerably affect patterns of gene flow among species.
Beyond Peto’s paradox: expanding the study of cancer resistance across species
Authors: Dujon Antoine M , Boddy Amy M , Hamede Rodrigo , Ujvari Beata , Thomas Frédéric 
Published: November 2024

Abstract
Peto’s paradox, which highlights the lower-than-expected cancer rates in larger and/or longer-lived species, is a cornerstone of discussions at the intersection of ecology, evolution, and cancer research. It prompts investigations into how species with traits that theoretically increase cancer risk manage to exhibit cancer resistance, with the ultimate goal of uncovering novel therapies for humans. Building on these foundational insights, we propose expanding the research focus to species that, despite possessing traits beyond size and longevity that theoretically increase their cancer risk, exhibit unexpected cancer resistance. Testing Peto’s paradox without interference from transient dynamics also requires considering species that are at an equilibrium between cancer risks and defenses, which is increasingly challenging due to anthropogenic activities. Additionally, we argue that transmissible cancers could significantly help in understanding how the metastatic process might be naturally suppressed. This research perspective is timely and aims to support the continued and in-depth identification of anti-cancer adaptations retained throughout evolution in the animal kingdom.
Megavariate methods capture complex genotype-by-environment interactions
Authors: Xavier Alencar , Runcie Daniel , Habier David 
Published: November 2024

Abstract
Genomic prediction models that capture genotype-by-environment (GxE) interaction are useful for predicting site-specific performance by leveraging information among related individuals and correlated environments, but implementing such models is computationally challenging. This study describes the algorithm of these scalable approaches, including 2 models with latent representations of GxE interactions, namely MegaLMM and MegaSEM, and an efficient multivariate mixed-model solver, namely Pseudo-expectation Gauss–Seidel (PEGS), fitting different covariance structures [unstructured, extended factor analytic (XFA), Heteroskedastic compound symmetry (HCS)]. Accuracy and runtime are benchmarked on simulated scenarios with varying numbers of genotypes and environments. MegaLMM and PEGS-based XFA and HCS models provided the highest accuracy under sparse testing with 100 testing environments. PEGS-based unstructured model was orders of magnitude faster than restricted maximum likelihood (REML) based multivariate genomic best linear unbiased predictions (GBLUP) while providing the same accuracy. MegaSEM provided the lowest runtime, fitting a model with 200 traits and 20,000 individuals in ∼5 min, and a model with 2,000 traits and 2,000 individuals in less than 3 min. With the genomes-to-fields data, the most accurate predictions were attained with the univariate model fitted across environments and by averaging environment-level genomic estimated breeding values (GEBVs) from models with HCS and XFA covariance structures.
Grandchild Care and Grandparents’ Well-Being in Context: The Impact of the COVID-19 pandemic
Authors: Bünning Mareike , Huxhold Oliver 
Published: November 2024

Abstract

Background and Objectives
This study investigates whether the association between supplementary grandchild care and grandparents’ subjective well-being—measured as life satisfaction, perceived stress, and loneliness—is moderated by the contextual environment. We use the coronavirus disease (COVID-19) pandemic as an example of contextual differences. Drawing on role theory, we argue that the costs and benefits of grandparenting may have differed between pandemic and prepandemic times. On the one hand, providing grandchild care during the pandemic may have been particularly stressful, prompting more negative effects on well-being. On the other hand, grandchild care may have been particularly relevant for enhancing well-being, as it protected grandparents from social isolation. Moreover, the association between grandparenting and well-being may have differed by gender.

Research Design and Methods
Using unbalanced panel data from the German Ageing Survey (DEAS) 2014 (n = 3,619), 2017 (n = 2,458), and 2020 (n = 2,021), we applied maximum likelihood structural equation modeling (ML-SEM)—a method that combines dynamic panel modeling with fixed-effects analysis—to examine whether there were differences in the relationship between grandchild care and grandparents’ well-being when comparing pandemic and prepandemic times and by grandparents’ gender.

Results
Grandchild care was associated with lower loneliness for both grandmothers and grandfathers. For grandfathers, this association was even stronger during the pandemic. Grandmothers experienced higher life satisfaction when taking care of grandchildren during the pandemic, but there was no evidence that grandchild care increased perceived stress for either grandmothers or grandfathers.

Discussion and Implications
In line with role enhancement theory, this study highlights that supplementary grandchild care can be beneficial for grandparents’ well-being. Moreover, the context in which grandchild care takes place shapes the costs and rewards associated with it. Our results suggest that supportive policies and programs facilitating grandchild care can enhance grandparents’ well-being, especially in challenging contexts.
Genetic and QTL analyses of sugar and acid content in sweet cherry (Prunus avium L.)
Authors: Gracia Clara , Calle Alejandro , Gasic Ksenija , Arias Esther , Wünsch Ana 
Published: November 2024

Abstract
Sweet cherry is very appreciated by consumers because of its attractive appearance and taste, which is determined by the balanced sweet–sour flavor. In this work, the genetics of soluble solid content (SSC), titratable acidity (TA), sugars, and organic acids was investigated in sweet cherry to facilitate breeding improvement for fruit quality. The fruits of five sweet cherry populations (N = 372), three F1 and two F2, were sampled over two years to evaluate SSC, TA, and the content of individual sugars (glucose, fructose, sorbitol, and sucrose) and organic acids (malic, quinic, oxalic, citric, and shikimic) by ultra-performance liquid chromatography. Glucose, followed by fructose, was the most abundant sugar, while malic acid was the predominant acid. Sorbitol and malic acid were the most stable compounds between years, and had the highest heritability, being also the best correlated to SSC and TA, respectively, revealing their relevance for breeding. Significantly positive correlations were observed among sugars and SSC, and acids and TA, but high interannual variability between years was observed for all traits. Quantitative trait loci (QTL) mapping for SSC, sugars, TA, and organic acids was performed using a multi-family approach with FlexQTL™. Twenty QTLs were detected consistently during the two phenotyped years, and several relevant regions with overlapping QTLs for sugars and acids were also identified. The results confirmed major stable SSC and TA QTLs on the linkage groups 4 and 6, respectively. Within the main LG4 SSC QTL region, where maturity and fruit development time QTLs have been previously detected, three stable sugar (glucose, sorbitol, and sucrose) and two acid (quinic, shikimic) QTLs were also identified, suggesting a pleiotropic effect of ripening date on the content of these compounds. The major malic acid QTL overlapped with TA QTL on LG6; thus, TA QTL mapping on LG6 may correspond to malic acid QTLs. Haplotype analyses of major SSC and sugars QTL on LG4, and TA and malic acid on LG6 revealed haplotypes of breeding interest. Several candidate genes previously identified in other Prunus fruit species, like peach, were found to collocate with the QTLs detected herein. This work reports QTLs regions and haplotypes of sugar and acid content in a Prunus nonclimacteric stone fruit for the first time.
Learning from the euro crisis: A new method of government for the European Union’s economic policy coordination after the pandemic
Authors: Fasone Cristina , Lupo Nicola 
Published: November 2024

Abstract
Has the European Union been able to learn from the experience of the euro crisis to shape its response to the economic consequences of the pandemic? This article aims to show that an effective learning process was set in motion in the aftermath of the pandemic emergency, although it looks still incomplete. To address the economic consequences of the COVID-19 outbreak and drawing on lessons from the euro crisis, a new method of government has been forged through the NextGenerationEU. Grounded in a creative interpretation of legal foundations and shaped by a process that is both national and European, involving domestic and supranational institutions, the governance of the Recovery and Resilience Facility (RRF) unfolds through the setting of EU-wide priorities, their articulation in national medium-term, performance-based plans, and continuous monitoring by the Commission to ensure compliance with multiple conditionality regimes. The first years of implementation of the RRF have proved successful not only for the use of the Fund by the member states but also for the spread of the RRF method of government in other areas of EU law, including the European Semester, REPowerEU, and the revised Stability and Growth Pact, despite the uncertainties surrounding the temporary nature of the instrument and some weaknesses in terms of democratic accountability.
High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer–testis antigen PRAME
Authors: Ribeiro Ana R , Britton-Rivet Camille , Collins Laura , Carreira Ricardo J , Moureau Sylvie , Benlahrech Adel , Stanhope Sarah , Harper Stephen , Liddy Nathaniel , Mahon Tara M , Petrovic Kristina , Fife Mark , Depoil David , Addis Philip , Bedke Nicole , Bouard Lucie , O’Dwyer Ronan , Gascoyne Duncan , Ranade Koustubh 
Published: November 2024

Abstract

Background
PRAME (Preferentially expressed Antigen in Melanoma) is a cancer–testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME+ tumors could be a novel immunotherapeutic option. We confirm that PRAME protein is expressed in cutaneous melanoma, including rare subtypes with limited treatment options, as well as primary and metastatic lung, breast, endometrial, and ovarian tumors. Furthermore, PRAME is expressed homogeneously across tumors with distinct oncogenic mutations, mutation burden, PD-L1 expression, immune infiltration, and features of immune checkpoint resistance. Immunopeptidomic analysis of primary tumors detected HLA class I-restricted PRAME peptides.

Methods
A TCR recognizing PRAME peptide SLLQHLIGL was engineered to high affinity and fused to a CD3 engaging domain to create a TCRxCD3 bispecific molecule (Immune-mobilizing monoclonal TCR Against Cancer, ImmTAC®) with the ability to redirect polyclonal T cells to efficiently kill PRAME+ cells.

Rs
The degree of T cell activation was positively correlated with peptide–HLA abundance, with as few as 10 epitopes per cell sufficient for target cell killing. Impaired ImmTAC®-redirected cytotoxicity of exhausted T cells was rescued using an anti-PD-1 antibody, supporting the use of a combination strategy to treat tumors with active PDL1-PD1 axes.

Conclusions
Our data demonstrate selective and efficient T cell activation and killing by a PRAME-directed TCRxCD3 bispecific, supporting further investigation in multiple cancer indications.
Bacterial and fungal components of the microbiome have distinct roles in Hawaiian drosophila reproduction
Authors: Medeiros Matthew J , Seo Laura , Macias Aziel , Price Donald K , Yew Joanne Y 
Published: November 2024

Abstract
The microbiome provides numerous physiological benefits for host animals. The role of bacterial members of microbiomes to host physiology is well-documented. However, much less is known about the contributions and interactions of fungal members, even though fungi are integral components of many microbiomes, including those of humans and insects. Here, we used antibacterial and antifungal drugs to manipulate the gut microbiome of a Hawaiian picture-wing Drosophila species, Drosophila grimshawi, and identified distinct effects for each treatment on microbiome community stability, reproduction, and lipid metabolism. Female oogenesis, fecundity, and mating drive were significantly diminished with antifungal treatment. In contrast, male fecundity was affected by antibacterial but not antifungal treatment. For males and females, simultaneous treatment with both antibacterial and antifungal drugs resulted in severely reduced fecundity and changes in fatty acid levels and composition. Microbial transplants using frass harvested from control flies partially restored microbiome composition and female fecundity. Overall, our results reveal that antibacterial and antifungal treatments have distinct effects on host fecundity, mating behavior, and lipid metabolism, and that interkingdom interactions contribute to microbial community stability and reproduction.