bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do protein language models learn phylogeny?
Authors: Tule Sanjana , Foley Gabriel , Bodén Mikael 
Published: February 2025

Abstract
Deep machine learning demonstrates a capacity to uncover evolutionary relationships directly from protein sequences, in effect internalising notions inherent to classical phylogenetic tree inference. We connect these two paradigms by assessing the capacity of protein-based language models (pLMs) to discern phylogenetic relationships without being explicitly trained to do so. We evaluate ESM2, ProtTrans, and MSA-Transformer relative to classical phylogenetic methods, while also considering sequence insertions and deletions (indels) across 114 Pfam datasets. The largest ESM2 model tends to outperform other pLMs (including the multimodal ESM3) by recovering phylogenetic relationships among homologous protein sequences in both low- and high-gap settings. pLMs agree with conventional phylogenetic methods in general, but more so for protein families with fewer implied indels, highlighting indels as a key factor differentiating classical phylogenetics from pLMs. We find that pLMs preferentially capture broader as opposed to finer evolutionary relationships within a specific protein family, where ESM2 has a sweet spot for highly divergent sequences, at remote distance. Less than 10% of neurons are sufficient to broadly recapitulate classical phylogenetic distances; when used in isolation, the difference between the paradigms is further diminished. We show these neurons are polysemantic, shared among different homologous families but never fully overlapping. We highlight the potential of ESM2 as a complementary tool for phylogenetic analysis, especially when extending to remote homologs that are difficult to align and imply complex histories of insertions and deletions. Implementations of analyses are available at https://github.com/santule/pLMEvo.
ESM-BBB-Pred: a fine-tuned ESM 2.0 and deep neural networks for the identification of blood–brain barrier peptides
Authors: Naseem Ansar , Alturise Fahad , Alkhalifah Tamim , Khan Yaser Daanial 
Published: February 2025

Abstract
Blood–brain barrier peptides (BBBP) could significantly improve the delivery of drugs to the brain, paving the way for new treatments for central nervous system (CNS) disorders. The primary challenge in treating CNS disorders lies in the difficulty pharmaceutical agent’s face in crossing the BBB. Almost 98% of small molecule drugs and nearly all large molecule drugs fail to penetrate the BBB effectively. Thus, identifying these peptides is vital for advancements in healthcare. This study introduces an enhanced intelligent computational model called BBB-PEP- Evolutionary Scale Modeling (ESM), designed to identify BBBP. The relative positions, reverse position and statistical moment-based features have been utilized on the existing benchmark dataset. For classification purpose, six deep classifiers such as fully connected networks, convolutional neural network, simple recurrent neural networks, long short-term memory (LSTM), bidirectional LSTM, and gated recurrent unit have been utilized. In addition to harnessing the effectiveness of the pre-trained model, a protein language model ESM 2.0 has been fine-tuned on a benchmark dataset for BBBP classification. Three tests such as self-consistency, independent set testing, and five-fold cross-validation have been utilized for evaluation purposes with evaluation metrics includes accuracy, specificity, sensitivity, and Matthews correlation coefficient. The fine-tuned model ESM 2.0 has shown superior results as compared to employed classifiers and surpasses the existing benchmark studies. This system will support future research and the scientific community in the computational identification of BBBP.
DECA: harnessing interpretable transformer model for cellular deconvolution of chromatin accessibility profile
Authors: Luo Shijie , Zhu Ming , Lin Liquan , Xie Jiajing , Lin Shihao , Chen Ying , Zhu Jiali , Huang Jialiang 
Published: February 2025

Abstract
The assay for transposase-accessible chromatin with sequencing (ATAC-seq) identifies chromatin accessibility across the genome, crucial for gene expression regulating. However, bulk ATAC-seq obscures cellular heterogeneity, while single-cell ATAC-seq suffers from issues such as sparsity and costliness. To this end, we introduce DECA, a sophisticated deep learning model based on vision transformer to deconvolve cell type information from bulk chromatin accessibility profiles, utilizing single-cell ATAC-seq datasets as reference for enhanced precision and resolution. Notably, patch attention generated by DECA’s multi-head attention mechanism aligns with chromatin interactions detected by Hi-C. Additionally, DECA predicted lineage-specific cell composition changes due to genetic perturbation. The chromatin accessibility signatures predicted by DECA are enriched with cell-type specific genetic variations. Ultimately, we applied DECA on pan-cancer ATAC-seq datasets and demonstrated its capability to deconvolve cell type proportions with clinical significance. Taken together, DECA deconvolves cellular proportions and predicts their chromatin accessibility profiles from bulk chromatin accessibility data, which enable exploring the gene regulatory programs in development and diseases.
Single cell multiome analysis of the bovine placenta identifies gene regulatory networks in trophoblast differentiation
Authors: Davenport Kimberly M , Lowke Makenzie T , Ortega M Sofia , Kelleher Andrew M , Warren Wesley C , Spencer Thomas E 
Published: February 2025

Abstract
A central determinant of successful reproduction is pregnancy establishment and maintenance that relies on proper development of the conceptus (embryo/fetus and associated extraembryonic membranes including the placenta). Pregnancy loss in cattle can be caused by inadequate development and differentiation of the placenta. However, the cellular and molecular mechanisms regulating bovine placenta development and, particularly, trophoblast differentiation are not well understood. Recent single-cell RNA-seq analyses revealed dynamic changes in cell populations and gene expression patterns during bovine placental development. Here, the chromatin accessibility landscape across diverse cell populations was determined in the developing (day 40) and mature (day 170) bovine placenta using the 10X Genomics multiome (snRNA-seq and snATAC-seq) platform. Analyses revealed distinct trophoblast, mesenchyme, endothelial, immune, and epithelial cell populations characterized by unique gene expression and chromatin accessibility signatures. ATAC-seq peaks defined open chromatin regions, facilitating the identification of transcription factor binding sites and candidate gene regulatory networks (GRN) involved with trophoblast differentiation. Several transcription factors, known for their involvement in trophoblast differentiation in other mammalian species, were identified as candidate regulators of uninucleate (UNC) to binucleate (BNC) trophoblast differentiation. This study adds to our foundational understanding of gene regulation and expression in the placenta, offering insights into the mechanisms governing pregnancy loss in cattle.
Suppression of FOXO3 by BMP signaling contribute to the different primordial germ cell proliferation between layers and broilers
Authors: Ma Yuxiao , Meng Lu , Wei Jiahui , Wu Wenhui , Zhang Yun , Wang Xuzhao , Guo Xiaotong , Wang Feiyi , Mao Yong , Zhu Guiyu 
Published: February 2025

Abstract
Although all domestic chicken breeds originate from their wild relatives, the red junglefowl, they have been selectively bred for high yields in egg or meat production， or both. Some breeds are highly efficient in egg production, while others perform poorly, due to long-term selection aimed for different purposes. Female primordial germ cells (PGCs) are the precursors of eggs and the population size of PGCs will ultimately determine ovarian reserve of hens. In this study, we observed that the layers exhibit greater proliferation capacity and a higher number of PGCs compared to the broilers before meiosis. By comparing the PGC transcriptomes between layers and broilers, we identified potential genes that regulate cell proliferation. We further confirmed that FOXO3 expression is higher in broilers, where it inhibits the PGC proliferation both in vivo and in vitro. However, in layers, the upstream BMP signaling stimulate the phosphorylation of AKT and suppress FOXO3 activity. Consequently, the elevated BMP signaling and reduced FOXO3 co-operatively promote more robust PGC proliferation in layers compared to broilers and result in a greater number of PGCs in layers. Our data not only reveal molecular mechanisms underlying PGC growth, but also provide new clues to improve the laying performance in chicken.
Differences in uterine and serum metabolome associated with clinical cure failure of metritis in dairy cows
Authors: Pereira F N S , Martelo Pereira A , Galvão K N , Bisinotto R S , Figueiredo C C 
Published: February 2025

Abstract
This study investigated differences in uterine and serum metabolome associated with clinical cure failure of metritis in dairy cows. Metritis was diagnosed in lactating Holstein cows from two Florida dairies and defined by the presence of fetid, watery, reddish-brown vaginal discharge from 4 to 12 days postpartum (dpp). Cows with metritis (n = 24) were paired with cows without metritis of similar parity and dpp (n = 24). On the day of metritis diagnosis (day 0), all cows with metritis received antimicrobial therapy. The continued presence of the fetid, watery, reddish-brown discharge on day 5 (n = 16) was defined as clinical cure failure, whereas clinical cure was defined by its absence (n = 8). Metabolome analyses of uterine lavage (days 0 and 5) and serum samples (day 0) were conducted using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were analyzed using partial least squares–discriminant analysis and ANOVA, adjusting P-values for multiple comparisons. Differences in the uterine metabolome on day 0 associated with clinical cure failure were linked to carbohydrate, amino acid, and lipid metabolism. Greater concentrations of arachidonic acid, ribose, and glutaric acid were associated with clinical cure failure, suggesting a greater degree of tissue lesion and inflammation. No differences in the serum metabolome were associated with cure failure. No differences in uterine metabolome were associated with clinical cure failure on day 5. The findings suggest that clinical cure failure is associated with a greater uterine inflammatory process that did not persist until cure assessment day.
Epigenetic age acceleration in peripheral blood correlates with brain-MRI age acceleration
Authors: Sant'Anna Barbosa Ferreira Pedro , van Dongen Jenny , den Braber Anouk , Boomsma Dorret I , de Geus Eco J C , van ‘t Ent Dennis 
Published: February 2025

Abstract
As the world's population ages, more and more people are expected to suffer from age-related diseases. Biological aging markers derived from DNA methylation and brain structure show promise in predicting health outcomes. Understanding the relationship between these biomarkers can promote the development of effective health interventions.
In a sample of 254 participants from the Netherlands Twin Register (20-84 years), we investigated associations between DNA methylation age acceleration based on five epigenetic biomarkers (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPACE) and brain age acceleration based on neuroimaging (brainageR). Furthermore, we applied bivariate twin models to examine the contribution of genetic and environmental factors to the associations (cross-twin cross-trait correlations and within monozygotic-twin pair differences).
We observed relationships with brain age acceleration for DNA methylation age acceleration based on the Hannum and GrimAge clocks that were supported by within MZ twin pair difference modelling. Cross-twin cross-trait modelling confirmed a non-shared environmental etiology.
Twin analyses highlight the importance of the environment in accelerated aging, raising the possibility for interventions such as lifestyle modification.
Advances in engineered organoid models of skin for biomedical research
Authors: Zeng Dongao , Li Shikai , Du Fangzhou , Xia Yuchen , Zhang Jingzhong , Yu Shuang , Qin Jianhua 
Published: February 2025

Abstract
In recent years, significant progress has been made in the development of organoids, which offer promising opportunities for developmental and translational research. With advances in cell biology and bioengineering techniques, skin models are evolving from conventional multilayered structures to appendage-bearing spheroids or 3D biomimetic models. This comprehensive review aims to provide an in-depth understanding of organoid models of the skin, covering topics such as skin development, construction strategies and key elements, types of organoid models, biomedical applications, and challenges. Embryonic skin development is briefly introduced to provide a foundational understanding of construction principles. Current engineering strategies are outlined, highlighting key elements such as cell sources, bioengineering techniques, 3D scaffolds, and crucial signaling pathways. Furthermore, recent advances in generating organoids with structural and functional parallels to native skin are meticulously summarized. These developments facilitate the utilization of organoids in diverse applications, such as modeling skin disorders, developing regenerative solutions, and understanding skin development. Finally, the challenges and prospects in the field are discussed. The integration of state-of-the-art bioengineering techniques with a deep understanding of skin biology is promoting the production and biomedical application of these organoid models.
“The FBI has no politics”: COMINFIL radio-TV and the suppression of dissent
Authors: Stabile Carol A , Tokos Lauren , Yousaf Miriam 
Published: February 2025

Abstract
In the second half of the 1940s, the Federal Bureau of Investigation initiated an investigation of the broadcasting industry that had far-reaching consequences for the future of television. This investigation, COMINFIL Radio-TV (short for Communist Infiltration of Radio-TV) provided justification and resources for the Bureau’s surveillance of progressives and efforts to attack and undermine progressive reforms in the postwar era. This article shows how the Bureau used the threat of communist infiltration to infiltrate trade unions, broadcast networks, and progressive organizations. In doing so, this article begins to address a crucial gap in Cold War media historiography—the Bureau’s interventions into broadcasting at a particularly critical moment in the development of television—by documenting government suppression of dissent and censorship.
Arm’s length or joined at the hip? Public service media’s coverage of Gaza
Authors: Forde Sydney L , Freedman Des 
Published: February 2025

Abstract
Critiquing normative articulations of a public versus commercial media binary, we explore the contradictory juxtaposition of democratic expectations assigned to public service media (PSM) broadly, alongside actual PSM reporting. We examine US and UK PSM coverage of two major events related to the bombardment of Gaza and subsequent humanitarian crisis in the months following the Hamas attacks on October 7, 2023. Contextualized within the UK, US and Israel’s historical and ongoing colonial violence within Palestine over the past 75 years, we assess coverage that stands in contradiction to the often fetishized notion of PSM’s role in serving a broadly conceived and normatively accepted “public,” and challenge the independence afforded to existing PSM structures via a critique of the notion that PSM organizations operate at “arm’s length” from government. Throughout our analysis, we find evidence of systematic failures and highlight PSM’s use as an instrument perpetuating state power and control.
Executive Summary: State-of-the-Art Review: Data and Trust to Improve Care for Transgender and Gender-Diverse Patients
Authors: Van Sickels Nicholas , Wong Jennifer W H , Villacorta-Cari Evelyn , Lee Steph E , Fallin-Bennett Keisa 
Published: February 2025

Abstract
As active medical and surgical providers of gender-affirming care, we aim to share lived experiences of our patients and outline best practices in gender-affirming medicine in this review.
Renal functional reserve in living kidney donors
Authors: Rinne Ana González , Sorensen Cristian Acosta , Reseghetti Elia , Viera Yaiza Rivero , Rincón Marian Stefany , Izquierdo Edduin Martín , Bethencourt Alejandro Alonso , Morales Adelaida , Moya Elisa Cabello , González Selene , Cabrera Faina González , Hernández Arminda Fariña , Lima Sergio Luis , Martín Laura Díaz , Escamilla Beatriz , Cruz Coriolano , Rinne Federico González , Tamajón Lourdes Pérez , Gaspari Flavio , Marrero Domingo Hernández , Porrini Esteban 
Published: February 2025

Abstract

Background
Factors associated with renal functional reserve (RFR)—presence or absence—are not completely clear and remain under-investigated.

Methods
In this observational study, we evaluated the characteristics associated with the presence or absence of RFR in healthy subjects—living kidney donors—before donation. Renal function was assessed with measured glomerular filtration rate (GFR)—the clearance of iohexol—and RFR with the infusion of amino acids. An increase in GFR &gt; 10% after amino acid infusion indicated the presence of RFR. We defined a priori three groups of donors: without, with, and using RFR. Subject using RFR had baseline GFR &gt;100 ml/min but without an increase in GFR after stimulation.

Results
Subjects without RFR were predominantly women (81%) with the lowest body surface area (BSA) (1.71 ± 0.17 m2), and basal GFR (85 ± 9 ml/min). Subjects with RFR were also mostly women (85%), with a higher BSA (1.83 ± 0.18 m2; p 0.039) and basal GFR (93 ± 15 ml/min). Subjects using RFR were mostly males (56%) and had the highest BSA (1.94 ± 0.18 m2; P &lt; 0.0001 vs without RFR; p ns vs with RFR), basal GFR (123 ± 20 ml/min; P &lt; 0.0001 vs subjects without RFR; P &lt; 0.0001 vs with RFR), and weight (82.1 ± 13.2 Kg; P &lt; 0.0001 vs without RFR; p ns vs with RFR).

Conclusions
The presence or absence of RFR was associated to differences in gender, weight, BMI, BSA, and basal GFR. Women with small BSA may have lower GFR and no RFR, indicating possibly a lower renal endowment even in the normal range of renal function. The use of RFR may indicate a response to a higher metabolic demand in subjects with higher renal endowment.
An investigation into the causes of race bias in AI-based cine CMR segmentation
Authors: Lee Tiarna , Puyol-Antón Esther , Ruijsink Bram , Roujol Sebastien , Barfoot Theodore , Ogbomo-Harmitt Shaheim , Shi Miaojing , King Andrew 
Published: February 2025

Abstract

Aims
Artificial intelligence (AI) methods are being used increasingly for the automated segmentation of cine cardiac magnetic resonance (CMR) imaging. However, these methods have been shown to be subject to race bias, i.e. they exhibit different levels of performance for different races depending on the (im)balance of the data used to train the AI model. In this paper we investigate the source of this bias, seeking to understand its root cause(s).

Methods and Results
We trained AI models to perform race classification on cine CMR images and/or segmentations from White and Black subjects from the UK Biobank and found that the classification accuracy for images was higher than for segmentations. Interpretability methods showed that the models were primarily looking at non-heart regions. Cropping images tightly around the heart caused classification accuracy to drop to almost chance level. Visualising the latent space of AI segmentation models showed that race information was encoded in the models. Training segmentation models using cropped images reduced but did not eliminate the bias. A number of possible confounders for the bias in segmentation model performance were identified for Black subjects but none for White subjects.

Conclusions
Distributional differences between annotated CMR data of White and Black races, which can lead to bias in trained AI segmentation models, are predominantly image-based, not segmentation-based. Most of the differences occur in areas outside the heart, such as subcutaneous fat. These findings will be important for researchers investigating performance of AI models on different races.
The Intergenerational Transmission of Welfare Dependency
Authors: de Haan Monique , Schreiner Ragnhild C 
Published: February 2025

Abstract
Exploiting rich administrative data from Norway, we estimate nonparametric bounds around the average causal effect of parental welfare participation on children’s welfare participation for children that grew up in welfare-dependent families. We find upper bounds well below the intergenerational association and substantially below existing LATE estimates in the literature. Our results show that a substantial portion of the observed intergenerational correlation in welfare dependency is due to selection, and that there is important heterogeneity in the intergenerational effects both between participants (and their children) within a welfare program, as well as across different welfare programs.
A comment on buyers’ miscoordination, entry, and downstream competition
Authors: Sevük Barış 
Published: February 2025

Abstract
Fumagalli and Motta (The Economic Journal, 2008) argue that competition among downstream buyers limits the ability of a dominant upstream firm to deter entry by a more efficient competitor. This comment demonstrates that the impact of downstream competition is, in fact, more complex. In particular, competition can motivate buyers to favor the incumbent due to a ‘raising rivals’ costs’ effect.
Morality in the Making: The Collaborative Relationship Between Formal Caregivers, Informal Caregivers and Nursing Home Residents
Authors: Dohmen Marleen D W , Visser Mandy , Huijg Johanna M , Groot Barbara C , Abma Tineke A 
Published: February 2025

Abstract

BACKGROUND AND OBJECTIVES
Collaboration between formal and informal caregivers is essential for providing good care to nursing home residents. Yet, ambiguity regarding mutual roles and responsibilities often impedes effective collaboration. To address this issue, we examined how formal caregivers, informal caregivers, and residents establish a moral understanding of their responsibilities, and how these understandings affect their triadic relationship.

RESEARCH DESIGN AND METHODS
We conducted a responsive evaluation including 28 semi-structured interviews with formal caregivers, informal caregivers, and residents. Walker’s expressive-collaborative model of morality (2007) was used as a theoretical lens to identify identities, values and roles in the triad.

RESULTS
Formal caregivers were assigned more moral responsibilities in the care process than residents and informal caregivers, particularly regarding decision-making authority. Formal caregivers considered this justified, while informal caregivers generally desired more influence. The attitude of residents on this matter remained relatively unclear. The diverging views on moral responsibilities between formal and informal caregivers led to relational tensions, impacting mutual trust and recognition between them.

DISCUSSION AND IMPLICATIONS
Walker’s model of morality provides a deeper understanding of the moral dynamics underlying the collaboration between formal caregivers, informal caregivers, and residents. Traditional hierarchies and a mismatch between healthcare and family ethics are implied to hinder informal caregiver involvement. Our findings call for practical and cultural adaptations on different levels within and outside nursing home organizations to improve the triadic collaborative relationship.