bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional annotation of regulatory elements in rainbow trout uncovers roles of the epigenome in genetic selection and genome evolution
Authors: Salem Mohamed , Al-Tobasei Rafet , Ali Ali , An Liqi , Wang Ying , Bai Xuechen , Bi Ye , Zhou Huaijun 
Published: December 2024

Abstract
Rainbow trout (RBT) has gained widespread attention as a biological model across various fields and has been rapidly adopted for aquaculture and recreational purposes on 6 continents. Despite significant efforts to develop genome sequences for RBT, the functional genomic basis of RBT’s environmental, phenotypic, and evolutionary variations still requires epigenome reference annotations.
This study has produced a comprehensive catalog and epigenome annotation tracks of RBT, detecting gene regulatory elements, including chromatin histone modifications, chromatin accessibility, and DNA methylation. By integrating chromatin immunoprecipitation sequencing, ATAC sequencing, Methyl Mini-seq, and RNA sequencing data, this new regulatory element catalog has helped to characterize the epigenome dynamics and its correlation with gene expression. The study has also identified potential causal variants and transcription factors regulating complex domestication phenotypic traits. This research also provides valuable insights into the epigenome’s role in gene evolution and the mechanism of duplicate gene retention 100 million years after RBT whole-genome duplication and during re-diploidization. The newly developed epigenome annotation maps are among the first in fish and are expected to enhance the accuracy and efficiency of genomic studies and applications, including genome-wide association studies, causative variation identification, and genomic selection in RBT and fish comparative genomics.
Learning a generalized graph transformer for protein function prediction in dissimilar sequences
Authors: Fu Yiwei , Gu Zhonghui , Luo Xiao , Guo Qirui , Lai Luhua , Deng Minghua 
Published: December 2024

Abstract

Background
In the face of a growing disparity between high-throughput sequence data and low-throughput experimental studies, the emerging field of deep learning stands as a promising alternative. Generally, many data-driven approaches are capable of facilitating fast and accurate predictions of protein functions. Nevertheless, the inherent statistical nature of deep learning techniques may limit their generalization capabilities when applied to novel nonhomologous proteins that diverge significantly from existing ones.

Results
In this work, we herein propose a novel, generalized approach named Graph Adversarial Learning with Alignment (GALA) for protein function prediction. Our GALA method integrates a graph transformer architecture with an attention pooling module to extract embeddings from both protein sequences and structures, facilitating unified learning of protein representations. Particularly noteworthy, GALA incorporates a domain discriminator conditioned on both learnable representations and predicted probabilities, which undergoes adversarial learning to ensure representation invariance across diverse environments. To optimize the model with abundant label information, we generate label embeddings in the hidden space, explicitly aligning them with protein representations. Benchmarked on datasets derived from the PDB database and Swiss-Prot database, our GALA achieves considerable performance comparable to several state-of-the-art methods. Even more, GALA demonstrates wonderful biological interpretability by identifying significant functional residues associated with Gene Ontology terms through class activation mapping.

Conclusions
GALA, which leverages adversarial learning and label embedding alignment to acquire domain-invariant protein representations, exhibits outstanding generalizability in function prediction for proteins from previously unseen sequence space. By incorporating the structures predicted by AlphaFold2, GALA demonstrates significant potential for function annotation in newly discovered sequences. A detailed implementation of our GALA is available at https://github.com/fuyw-aisw/GALA.
Stratum corneum nanotexture feature detection using deep learning and spatial analysis: a noninvasive tool for skin barrier assessment
Authors: Wang Jen-Hung , Pereda Jorge , Du Ching-Wen , Chu Chia-Yu , Christensen Maria Oberländer , Kezic Sanja , Jakasa Ivone , Thyssen Jacob P , Satheesh Sreeja , Hwu Edwin En-Te 
Published: December 2024

Abstract

Background
Corneocyte surface nanoscale topography (nanotexture) has recently emerged as a potential biomarker for inflammatory skin diseases, such as atopic dermatitis (AD). This assessment method involves quantifying circular nano-size objects (CNOs) in corneocyte nanotexture images, enabling noninvasive analysis via stratum corneum (SC) tape stripping. Current approaches for identifying CNOs rely on computer vision techniques with specific geometric criteria, resulting in inaccuracies due to the susceptibility of nano-imaging techniques to environmental noise and structural occlusion on the corneocyte.

Results
This study recruited 45 AD patients and 15 healthy controls, evenly divided into 4 severity groups based on their Eczema Area and Severity Index scores. Subsequently, we collected a dataset of over 1,000 corneocyte nanotexture images using our in-house high-speed dermal atomic force microscope. This dataset was utilized to train state-of-the-art deep learning object detectors for identifying CNOs. Additionally, we implemented a kernel density estimator to analyze the spatial distribution of CNOs, excluding ineffective regions with minimal CNO occurrence, such as ridges and occlusions, thereby enhancing accuracy in density calculations. After fine-tuning, our detection model achieved an overall accuracy of 91.4% in detecting CNOs.

Conclusions
By integrating deep learning object detector with spatial analysis algorithms, we developed a precise methodology for calculating CNO density, termed the Effective Corneocyte Topographical Index (ECTI). The ECTI demonstrated exceptional robustness to nano-imaging artifacts and presents substantial potential for advancing AD diagnostics by effectively distinguishing between SC samples of varying AD severity and healthy controls.
Practitioners’ perspectives on unintended effects of illicit drug use prevention public service announcements in Australia
Authors: Munro Kirsteen , Bogomolova Svetlana , Simmonds Lucy 
Published: December 2024

Abstract
Public service announcements (PSAs) or campaigns aimed at preventing harm can inadvertently risk creating additional harms. It remains unclear whether these unintended effects are considered during campaign development, if risk mitigation strategies are implemented, or how professionals involved perceive these issues. It is in the context of illicit drug use prevention PSAs that our research investigates and explores the perspectives of practitioners—health support professionals and advertising campaign designers and creators. Semi-structured expert interviews were conducted to capture and synthesize practitioners’ perspectives which were then analysed by applying a framework to address the unintended effects of public health interventions. The results indicated that practitioners from both sectors are aware of unintended harms but place varying levels of importance on different aspects. In the case of illicit drug prevention PSAs, incorporating practitioners’ perspectives in campaign development may result in mitigating the risk of potential unintended harmful effects.
Genetic architecture of RNA editing, splicing and gene expression in schizophrenia
Authors: Choudhury Mudra , Yamamoto Ryo , Xiao Xinshu 
Published: December 2024

Abstract
Genome wide association studies (GWAS) have been conducted over the past decades to investigate the underlying genetic origin of neuropsychiatric diseases, such as schizophrenia (SCZ). While these studies demonstrated the significance of disease-phenotype associations, there is a pressing need to fully characterize the functional relevance of disease-associated genetic variants. Functional genetic loci can affect transcriptional and post-transcriptional phenotypes that may contribute to disease pathology. Here, we investigate the associations between genetic variation and RNA editing, splicing, and overall gene expression through identification of quantitative trait loci (QTL) in the CommonMind Consortium SCZ cohort. We find that editing QTL (edQTL), splicing QTL (sQTL) and expression QTL (eQTL) possess both unique and common gene targets, which are involved in many disease-relevant pathways, including brain function and immune response. We identified two QTL that fall into all three QTL categories (seedQTL), one of which, rs146498205, targets the lincRNA gene, RP11-156P1.3. In addition, we observe that the RNA binding protein AKAP1, with known roles in neuronal regulation and mitochondrial function, had enriched binding sites among edQTL, including the seedQTL, rs146498205. We conduct colocalization with various brain disorders and find that all QTL have top colocalizations with SCZ and related neuropsychiatric diseases. Furthermore, we identify QTL within biologically relevant GWAS loci, such as in ELA2, an important tRNA processing gene associated with SCZ risk. This work presents the investigation of multiple QTL types in parallel and demonstrates how they target both distinct and overlapping SCZ-relevant genes and pathways.
The role of miR-129-5p in regulating γ-globin expression and erythropoiesis in β-thalassemia
Authors: Li Jingmin , Chen Meihuan , Zhao Wantong , Lv Aixiang , Lin Siyang , Zheng Yanping , Cai Meiying , Lin Na , Xu Liangpu , Huang Hailong 
Published: December 2024

Abstract
The regulation of γ-globin expression is crucial due to its beneficial effects on diseases like β-thalassemia and sickle cell disease. B-cell lymphoma/leukemia 11A (BCL11A) is a significant suppressor of γ-globin, and microRNAs (miRNAs) targeting BCL11A have been shown to alleviate this suppression. In our previous high-throughput sequencing, we identified an 11.32-fold increase in miR-129-5p expression in β-thalassemia patients. However, the regulatory mechanisms of miR-129-5p in the context of erythroid differentiation remain to be elucidated. Our study aimed to elucidate the role of miR-129-5p in γ-globin regulation and erythropoiesis. We measured miR-129-5p levels in peripheral blood from β-thalassemia major and intermedia patients. Fluorescence in situ hybridization, dual-luciferase reporter assays, miRNA pull down assays and western blot analyses were conducted to examine the effects of miR-129-5p on γ-globin expression and BCL11A repression. Cell proliferation, apoptosis, and erythroid differentiation were assessed using cell counting kit-8, Wright-Giemsa, and benzidine staining, and flow cytometry assays. The expression levels of miR-129-5p were significantly elevated in β-thalassemia patients and positively correlated with γ-globin synthesis while negatively correlating with liver damage. miR-129- 5p enhanced γ-globin gene expression in K562 and HUDEP-2 cells by effectively repressing BCL11A. Overexpression of miR-129-5p inhibited cell proliferation, induced cell cycle arrest at the G1/G0 phase, promoted apoptosis and stimulated erythroid differentiation and maturation. Conversely, inhibition of miR-129-5p produced opposite cellular effects. miR-129-5p acts as a positive regulator of erythroid differentiation and γ-globin synthesis. It offers a promising miRNA target for activating the γ-globin gene and reducing ineffective erythropoiesis in β-thalassemia patients.
Genome scans reveal extensive population structure in three neritic tuna and tuna-like species in the Indian Ocean
Authors: Feutry Pierre , Foster Scott , Grewe Peter M , Aulich Jorden , Lansdell Matt , Clear Naomi , Cooper Scott , Williams Ashley , Johnson Grant , Dilrukshi Thilini , Wudianto  , Shahid Umair , Ahusan Mohamed , Lestari Pratiwi , Taufik Muhammad , Priatna Asep , Zamroni Achmad , Usmani Hamid Badar , Farley Jessica , Murua Hilario , Marsac Francis , Davies Campbell R 
Published: December 2024

Abstract
Neritic tunas and tuna-like species are an important resource for many coastal nations1 worldwide supporting both commercial and artisanal fisheries, but little is known about their population structure at a spatial scale required for effective fisheries management. In this study, we use Next Generation Sequencing methods to investigate the genetic connectivity of three major neritic tuna and tuna-like species in the Indian Ocean: Longtail Tuna (Thunnus tonggol), Kawakawa (Euthynnus affinis), and narrow-barred Spanish mackerel (Scomberomorus commerson). We sampled 293 Longtail Tuna from three locations, 362 Kawakawa from seven locations, and 210 narrow-barred Spanish mackerel from six locations. Genetic data showed clear evidence of heterogeneity in all three species, and patterns of isolation-by-distance were detected in Kawakawa and narrow-barred Spanish mackerel. Pairwise FST estimates of population differentiation and model-based grouping (mixture models) revealed that (i) individuals of Longtail Tuna from each sampling location belonged to a distinct genetic group, (ii) at least two different groups of Kawakawa were identified, and (iii) at least four groups of narrow-barred Spanish mackerel were identified across the sampled range within the north and eastern Indian Ocean. These results demonstrate that neritic tunas exhibit genetic structuring at small to medium spatial scales that need to be considered in the design of monitoring and assessment systems for fisheries management purposes in the northern and eastern parts of their range in the Indian Ocean. Further sampling, at a finer spatial resolution within the range of the current study, and across the north-western and western parts of their range of the Indian Ocean that were not covered in the current study, is required to provide a comprehensive understanding of the number of populations present and the spatial extent of individual populations in the Indian Ocean and adjacent seas.
Impact of aetiology on short- and long-term outcomes in open descending and thoracoabdominal aneurysm repair
Authors: Chen Joshua R , Pritting Christopher , Shah Vishal N , King Colin , McGee Jacqueline , Plestis Konstadinos A 
Published: December 2024

Abstract

OBJECTIVES
We analysed the impact of chronic type B aortic dissection (cTBAD) and degenerative aneurysm (DA) on the short- and long-term outcomes of patients undergoing open descending thoracic aortic aneurysm and thoracoabdominal aortic aneurysm repair.

METHODS
We performed a retrospective analysis of a prospectively maintained aortic database. From 1999 to 2023, 245 patients underwent open descending thoracic aortic aneurysm or thoracoabdominal aortic aneurysm repair. We compared preoperative comorbidities, postoperative complications and operative and long-term mortality for patients with cTBAD (120 patients, 49%) and DA (125 patients, 51%).

RESULTS
Patients with cTBAD were significantly younger, more likely to be male and less likely to have comorbidities including diabetes, chronic obstructive pulmonary disease and coronary artery disease. There were no statistically significant differences in the incidence of operative mortality between cTBAD (7.5%) and DA patients (11.2%) (P = 0.44). Survival at 1, 5, 10 and 15 years for cTBAD versus DA patients was 90% versus 76%, 79% versus 59%, 59% versus 42% and 50% versus 29%, respectively (P &lt; 0.01); however, this lost statistical significance in the Cox regression (P = 0.86). Following multivariable analysis, older age, female gender, coronary artery disease, urgent or emergent procedure and descending thoracic aortic aneurysm were independent predictors of long-term outcomes.

CONCLUSIONS
There were no statistically significant differences in the incidence of postoperative complications, operative deaths and long-term survival between cTBAD and DA patients.

IRB number
(#20D.802), Obtained: 1/31/23.
Risk Stratification of Metabolic Risk Factors and Statin Use Associated With Liver and Nonliver Outcomes in Chronic Hepatitis B
Authors: Zhang Xinrong , Nguyen Vy H , Kam Leslie Yeeman , Barnett Scott D , Henry Linda , Cheung Ramsey , Nguyen Mindie H 
Published: December 2024

Abstract

Background
We investigated the association of metabolic risk factors (MRFs) and statin use with liver and nonliver outcomes in a nationwide cohort of patients with chronic hepatitis B (CHB) in the United States.

Methods
We conducted a retrospective cohort study of adult patients with CHB using the MarketScan Databases (January 2007–December 2021). Incidence of liver and nonliver outcomes (cardiovascular disease, chronic kidney disease, and extrahepatic cancer) was analyzed. MRFs included diabetes mellitus (DM), hypertension, hyperlipidemia, and obesity.

Results
The study included 52 277 patients with CHB, and 1:1 propensity score matching yielded 16 696 pairs of matched patients with and without MRFs for analysis. When compared with those without MRFs, patients with DM and all 3 other MRFs had the highest adjusted hazard ratio (95% CI) for any liver outcome at 2.08 (1.22–3.52), followed by 12.98 (7.73–21.80) for cardiovascular disease, 9.25 (5.46–15.66) for chronic kidney disease, and 2.01 (1.00–4.04) for extrahepatic cancer. Increased metabolic burden was associated with liver and nonliver outcomes except for comparison between patients without MRFs and those with MRFs but no DM (P &gt; .2 for all liver outcomes). Among lower metabolic burden (≤2 MRFs), statin use was associated with a 15% lower risk of any liver outcomes, 35% reduced risk of HCC, and 15% lower risk of cirrhosis but not among those with higher metabolic burden (≥3 MRFs).

Conclusions
Higher metabolic burden was associated with a greater risk for liver and nonliver complications in patients with CHB, with DM having the highest impact among other MRFs. Statin use was associated with a reduced risk of liver outcomes among lower metabolic burden.
Direct-Acting Antivirals Quickly Eradicate Hepatitis C Virus From the Liver in People With Human Immunodeficiency Virus but Do Not Fully Reverse Immune Activation
Authors: Sachithanandham Jaiprasath , Leep-Lazar Julia , Quinn Jeffrey , Bowden Kenneth , Balasubramaniam Prasanthy , Ward Kathleen , Ribeiro Ruy M , Sulkowski Mark S , Balagopal Ashwin 
Published: December 2024

Abstract

Background
Hepatitis C virus (HCV) infects nearly one-fourth of people with human immunodeficiency virus (HIV). The role of direct-acting antivirals (DAAs) on immune activation in people with HIV (PWH) and HCV is poorly understood.

Methods
We quantified plasma HCV RNA and CXCL10 in persons with HCV monoinfection versus HIV/HCV coinfection receiving sofosbuvir-velpatasvir. Single-cell laser capture microdissection was applied to liver biopsies obtained before and within 4–7 days of DAA initiation to estimate HCV clearance and changes in interferon-stimulated genes (ISGs).

Results
We enrolled 10 people with chronic genotype 1a HCV: 5 were PWH with ART-suppressed viremia and CD4+ T cell counts &gt;200 cells/µL. First- and second-phase plasma HCV RNA kinetics were not different between groups. Median (min–max) proportions of infected hepatocytes at biopsy 1 were 0.06 (0.01–0.59) in HCV monoinfection and 0.21 (0.04–0.87) in HIV/HCV coinfection and did not differ. Participants had lower intracellular HCV RNA levels at biopsy 2. CXCL10 levels declined in both groups but were higher in coinfection than in monoinfection even at the end of treatment. The proportion of cells expressing ISGs diminished in monoinfection but increased in coinfection.

Conclusions
Whereas DAAs rapidly cleared intrahepatic HCV in both groups, immune activation was slower to diminish in PWH. Residual immune activation in PWH warrants further exploration.
Clinical Trials Registration. NCT02938013.
IL-5-producing Group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils
Authors: Yanagibashi Tsutomu , Ikutani Masashi , Nagai Terumi , Arita Makoto , Watanabe Yasuharu , Nagai Yoshinori , Takatsu Kiyoshi 
Published: December 2024

Abstract
Intestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in the intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria. Interleukin (IL)-5 is constitutively produced by Group 2 innate lymphoid cells (ILC2s) and plays a critical role in the survival and proliferation of B cells and eosinophils. Here, we show the role of IL-5-producing ILC2s in intestinal TI IgA production at steady state using T cell receptor α deficient mice. In this mouse model, ILC2s increased fecal TI IgA levels in a non-inflammatory state in an IL-5-dependent manner. The administration of recombinant IL-33 (rIL-33) increased the amount of TI IgA production, accompanied by an increase in the number of IL-5-producing ILC2s in the large intestine. In addition, rIL-33 treatment increased IL-5-dependent IgA+ cells in isolated lymphoid follicles, the site of TI IgA production. Furthermore, eosinophils recruited by ILC2s were required for the maximal production of IgA in the TI pathway. Moreover, IL-5 increased the frequency of TI IgA-binding intestinal bacteria and was involved in the maintenance of intestinal bacterial composition. These findings indicate that IL-5-producing ILC2s together with eosinophils contribute to TI IgA production. In addition to their role in TI IgA production, IL-5-producing ILC2s may contribute to the homeostasis of intestinal commensal bacteria.
Tracing active members in microbial communities by BONCAT and click chemistry-based enrichment of newly synthesized proteins
Authors: Hellwig Patrick , Kautzner Daniel , Heyer Robert , Dittrich Anna , Wibberg Daniel , Busche Tobias , Winkler Anika , Reichl Udo , Benndorf Dirk 
Published: December 2024

Abstract
A comprehensive understanding of microbial community dynamics is fundamental to the advancement of environmental microbiology, human health, and biotechnology. Metaproteomics, defined as the analysis of all proteins present within a microbial community, provides insights into these complex systems. Microbial adaptation and activity depend to an important extent on newly synthesized proteins (nP), however, the distinction between nP and bulk proteins is challenging. The application of BONCAT with click chemistry has demonstrated efficacy in the enrichment of nP in pure cultures for proteomics. However, the transfer of this technique to microbial communities and metaproteomics has proven challenging and thus it has not not been used on microbial communities before. To address this, a new workflow with efficient and specific nP enrichment was developed using a laboratory-scale mixture of labelled Escherichia coli and unlabeled yeast. This workflow was then successfully applied to an anaerobic microbial community with initially low bioorthogonal non-canonical amino acid tagging efficiency. A substrate shift from glucose to ethanol selectively enriched nP with minimal background. The identification of bifunctional alcohol dehydrogenase and a syntrophic interaction between an ethanol-utilizing bacterium and two methanogens (hydrogenotrophic and acetoclastic) demonstrates the potential of metaproteomics targeting nP to trace microbial activity in complex microbial communities.