bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Recessiveoca2Mutation Underlies Albinism inXiphophorusfish
Authors: Xing Yanting , Boswell William , Parker Jessica , Du Kang , Schartl Manfred , Lu Yuan 
Published: January 2025

AbstractOculocutaneous albinism (OCA) is a group of genetic disorders characterized by impaired melanin production, leading to reduced pigmentation in the skin, hair, and eyes.Xiphophorus, a genus of small freshwater fish, has been a pivotal model organism in pigmentation disorder research, providing key findings in the genetic pathways governing physiological and pathological pigment cell biology. Leveraging the well-established research framework provided byXiphophorus, we have identified a spontaneously occurring albinism phenotype in swordtail fishXiphophorus hellerii. Genetic mapping of albino fish showed that albinism is associated with a recessive mutation in theoca2gene. This discovery provides a novel opportunity to explore functions ofoca2gene in pigment cell differentiation, pigment synthesis, melanosome assembly and transportation function and amelanotic melanoma development.
Volatile-suppressed peptide signaling enhances volatile responses in plant-plant interactions
Authors: Wang Lei , Hoefer Sara , Jimenez-Sandoval Pedro , Yu Hao , Spiegelhalder Roxane , Waterman Jamie , Hurni Luke , Hu Lingfei , Liu Lei , Jackson David , Raissig Michael , Erb Matthias 
Published: January 2025

AbstractPlant volatiles shape plant-plant interactions by acting as defense regulators and response factors. While plant volatile biosynthesis is well understood, how their emission is regulated remains largely elusive. Here, we show that small peptide signaling regulates induced volatile release in maize. Following herbivore attack, green leaf volatiles such as (Z)-3-hexenyl acetate (HAC) are released and induce terpene and indole emissions from neighboring plants. This process is accompanied by reduced expression of the ZmCLE1E9 gene and the ZmBAM1A, ZmBAM1B and ZmBAM3C receptor genes in HAC-exposed plants. Exogenous ZmCLE1E9 peptide inhibits HAC-triggered volatile release by limiting stomatal aperture. This inhibition disappears in theZmbam1a/Zmbam1b/Zmbam3ctriple mutant. Molecular docking supports ZmCLE1E9 and ZmBAMs as ligand-receptor pairs. Furthermore,Zmcle1e9andZmbamstriple mutants show increased volatile emissions upon HAC exposure. In summary, we show that upon HAC perception, maize plants enhance their capacity to release terpenes and indole via the suppression of CLE1E9 signaling. This behavior allows maize plants to rapidly deploy volatile cues in response to stress volatiles and thus shape the infochemical dynamics of multitrophic environments.
Rare variants and founder effect in an understudied Quebec population
Authors: Gagnon Mylène , Moreau Claudia , Ricard Jasmin , Boisvert Marie-Claude , Bureau Alexandre , Maziade Michel , Girard Simon L. 
Published: January 2025

AbstractFounder events influenced the genetic diversity within the Quebec province, increasing the frequency of certain rare pathogenic variants in regional populations. Some regions such as Beauce remain understudied despite evidence of a regional founder effect. Leveraging extensive genealogical data, we found a specific regional structure emerging in Beauce following the initial settlement, with a gradual increase of the inbreeding and kinship coefficients and a low ancestors’ diversity. Profiting from the genetic distinctiveness of the region, we identified 28 rare pathogenic variants with higher carrier rates in Beauce than in urban regions due to its regional founder effect. This provides the first in-depth study of Beauce’s genetic and genealogical landscape, revealing a distinct structure and suggesting that other overlooked regions, in Quebec and elsewhere, could benefit from fine-scale population structure study to improve the understanding and management of rare diseases.
VR-based Gamma Sensory Stimulation: A feasibility study
Authors: Reis C. , Azizollahi H. , Headley G. , Navarro S. , Hanslmayr S. , Clouter A. , Zanto T , Certain R. 
Published: January 2025

AbstractAlzheimer’s disease (AD) presents a critical global health challenge, with current therapies offering limited efficacy and safety in halting disease progression. Gamma sensory stimulation (GSS) has emerged as a promising non-invasive neuromodulation technique that enhances gamma neural synchrony, potentially counteracting AD pathology by reducing neuroinflammation, promoting glymphatic clearance, and improving synaptic plasticity. However, existing GSS delivery methods rely on simplistic sensory stimuli that lack user engagement, creating adherence barriers and limiting the full therapeutic potential of GSS.This pilot study assessed the feasibility, safety, and efficacy of delivering GSS via virtual reality (VR), combining EEG recordings to monitor neural activity and a digital questionnaire to evaluate safety and tolerability. Sixteen cognitively healthy older adults participated in three experiments designed to assess modulation of gamma activity in response to 40Hz stimuli. EEG recordings confirmed that unimodal auditory and visual stimuli reliably induced gamma oscillations in their respective cortical regions, while multimodal stimulation enhanced both gamma power and inter-trial phase coherence, demonstrating robust modulation of gamma activity. Notably, significant gamma activity modulation was also achieved when diversified multimedia content was modulated at 40Hz and integrated into a cognitive task, highlighting the flexibility and effectiveness of this approach.The findings of this study validate VR as a scalable tool for delivering engaging and cognitively relevant GSS, paving the way for personalized therapies that maximize adherence and therapeutic outcomes. By integrating interactive elements, VR-based GSS may uniquely target memory-related neural networks, offering a novel approach to mitigate neurotoxicity and cognitive decline in AD.
Proteome changes associated with effect of high-dose single-fractionation radiation on lung adenocarcinoma cell lines
Authors: Leis Elina , Modhukur Vijayachitra , Lust Helen , Vardja Markus , Saarma Merilin , Ilves Ivar , Jaal Jana , Lavogina Darja 
Published: January 2025

AbstractLung cancer is a leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) representing 85% of cases. Advances in treatment modalities, including the emergence of antibody-drug conjugates and stereotactic radiation therapy, have improved outcomes. However, the possible synergistic effects of these therapies remain underexplored at the molecular level. This study investigated high-dose radiation-induced proteomic changes in lung adenocarcinoma cell line HCC-44 grown adherently and cell line A549, grown as adherent cells and 3D spheroids. Our hypothesis was that proteins upregulated by 10 Gy irradiation serve as resistance drivers in cancerous cells and can thus represent potential therapeutic targets.The label-free mass spectrometry revealed distinct proteomic responses to 10 Gy irradiation, varying by cell line and culturing conditions. Differentially expressed proteins elevated in the irradiated samples included ephrin type-A receptor 2 (EPHA2) in adherent cells and insulin-like growth factor 2 receptor (IGF2R), tetraspanin 3 (TSPAN3) as well as cathepsin D (CTSD) in spheroids. The validation of these targets was carried outviaWestern blot, immunofluorescence, viability assay and spheroid formation assay. The functional assays demonstrated that irradiation sensitized A549 cells to EPHA2 and CTSD inhibitors. These findings underscore the potential of integrating radiation and targeted therapies in NSCLC treatment, and highlight EPHA2 as a promising candidate for future therapeutic strategies.
iPSC-derived hepatocytes accurately recapitulate population diversity in alpha-1-antitrypsin deficiency and offer a novelin vitromodel for large-scale drug efficacy screening studies
Authors: Gil Carlos , Papastavrou Vanesa , Gatti Gemma , Chung Samuel , Kiloh George , Cheung Ka , Łukasiak Magdalena , Robinson Chloe , Panman Lia , Kasioulis Ioannis , Nikolaou Nikolaos 
Published: January 2025

AbstractBackgroundAlpha-1 antitrypsin deficiency (A1ATD) is a hereditary recessive disorder caused by mutations in theSERPINA1gene. It is a clinically under-recognised disease characterised by low circulating A1AT levels and intracellular accumulation of misfolded A1AT in hepatocytes. Deposition of excessive abnormal A1AT in the liver leads to liver failure, yet no specific treatments are available due to the lack of physiologically relevant disease modelling platforms.MethodsWe have hypothesised that human induced pluripotent stem cell (iPSC)-derived hepatocytes can provide an efficient platform to study A1ATD. Using CRISPR/Cas9, we have generated wild-type and A1ATD iPSC-derived hepatocytes (Opti-HEP) from healthy and A1ATD donors and developed a bioassay that mimics the accumulation of misfolded A1AT in the liver. Responses to the reference drug carbamazepine (CBZ), known to reduce intracellular misfolded A1AT levels, and RNA-based therapeutics were subsequently investigated.ResultsAll lines successfully differentiated into hepatocytes as measured by comparable key hepatic and disease markers to those seen in primary human hepatocytes. The diseased lines displayed increased intracellular accumulation of misfolded A1AT compared to isogenic controls. Diseased cell lines showed significant decreases in intracellular accumulation of polymeric A1AT following transfection with RNA-based therapeutics, but a differential response upon treatment with CBZ.ConclusionWe have developed a specific and robustin vitromodel of A1ATD that recapitulates disease pathophysiology and responds to small molecule-based treatments and advanced therapeutic strategies. These data demonstrate the suitability of this model for large-scale efficacy screening studies for the treatment of A1ATD and help pave the way towards the development of novel therapies.
Regulation of hematopoietic stem cell (HSC) proliferation by Epithelial Growth Factor Like-7 (EGFL7)
Authors: Kulkarni Rohan , Goda Chinmayee , Rudich Alexander , Karunasiri Malith , Urs Amog P , Bustos Yaphet , Balcioglu Ozlen , Li Wenjun , Chidester Sadie , Rodgers Kyleigh A , Garfinkle Elizabeth AR , Patel Ami , Miller Katherine E , Popovich Phillip G , Elf Shannon , Garzon Ramiro , Dorrance Adrienne M 
Published: January 2025

ABSTRACTUnderstanding the pathways regulating normal and malignant hematopoietic stem cell (HSC) biology is important for improving outcomes for patients with hematologic disorders. Epithelial Growth Factor Like-7 (EGFL7)is ∼30 kDa secreted protein that is highly expressed in adult HSCs. UsingEgfl7genetic knock-out (Egfl7KO) mice and recombinant EGFL7 (rEGFL7) protein, we examined the role of Egfl7 in regulating normal hematopoiesis. We found thatEgfl7KO mice had decreases in overall BM cellularity resulting in significant reduction in the number of hematopoietic stem and progenitor cells (HSPCs), which was due to dysregulation of normal cell-cycle progression along with a corresponding increase in quiescence. rEGFL7 treatment rescued our observed hematopoietic defects ofEgfl7KO mice and enhanced HSC expansion after genotoxic stress such as 5-FU and irradiation. Furthermore, treatment of WT mice with recombinant EGFL7 (rEGFL7) protein expands functional HSCs evidenced by an increase in transplantation potential. Overall, our data demonstrates a role for EGFL7 in HSC expansion and survival and represents a potential strategy for improving transplant engraftment or recovering bone marrow function after stress.
The RNA-binding protein RSRC2 promotes mitotic fidelity by interacting with the lncRNAC1QTNF1-AS1
Authors: Georgieva Kaliya , Coomer Alice O , Babaei Parnia , Guiducci Giulia , Dodel Martin , Maniati Eleni , Thind Anisha , Krishnamurthy Sneha , Nawrocka Anna , Wallis Sam , Shkumatava Alena , Wang Jun , Mardakheh Faraz K , Stojic Lovorka 
Published: January 2025

AbstractMitotic fidelity depends on proper chromosome alignment at the spindle equator, a process known as chromosome congression, driven by well-established protein networks. Whereas RNA-binding proteins and noncoding RNAs have been implicated in cell division, their interplay during this process remains unknown. Here, we discover that RSRC2, an arginine/serine-rich RNA-binding protein, plays an essential role in cell division by interacting with the long non-coding RNAC1QTNF1-AS1. The loss of either RSRC2 orC1QTNF1-AS1results in defects in chromosome congression and mitotic progression. We show that RSRC2 interacts with distinct sets of proteins involved in splicing and centrosome biogenesis, contributing to the fidelity of cell division through two different mechanisms: one linked to the splicing of mitotic regulators and the other by localising to mitotic centrosomes for which the interaction with theC1QTNF1-AS1RNA is required. Our study uncovers RSRC2 as a new regulator of cell division and illustrates how RNA-protein complexes promote error-free mitosis.
Jk DNA GAGA MOTIFS ARE REQUIRED FOR LOCAL NUCLEOSOME REMODELING AND Vk-Jk RECOMBINATION
Authors: Veselits Margaret , McLean Kaitlin , Wright Nathaniel E , Okoreeh Michael , Maienschein-Cline Mark , Mandal Malay , Clark Marcus 
Published: January 2025

AbstractImmunoreceptor gene recombination requires complementary 12 bp and 23 bp recombination signal sequences (RSSs). In addition, the RSSs that assemble the RAG proteins, recombination centers, must be accessible yet flanked by a 5’ nucleosome decorated with H3K4me3. InDrosophila, DNA GAGA motifs play an important role in nucleosome positioning. Herein, we report that 5’ to each functional Jk RSS is a DNA GAGA motif conserved across mammalian species. In mice, the GAGA motif 5’ to Jk1 regulated local RSS accessibility and 5’ nucleosome placement. Furthermore, it was required for Vk-Jk1 recombination. Murine Jk3 is nonfunctional, having mutations in both RSS and GAGA motifs. Restoring both GAGA and RSS motifs rescued Vk-Jk3 recombination. In contrast, restoring the RSS alone did not. Genome-wide, strong cryptic 23 RSSs were preferentially bound to nucleosomes. Furthermore, evolutionary selection against cRSS only occurred in the A Compartment of B lymphocytes, not embryonic stem cells. These data indicate that in developing B cells, nucleosome positioning both enables and restricts recombination to Jk. Furthermore, our data suggest an expanded definition of recombination center-associated RSSs to include a 5’ GAGA sequence that dictates the local epigenetic state required for gene recombination.SummaryRecombination center assembly requires a specific epigenetic topology at recombination signal sequences. Herein, we report that conserved GAGA motifs 5’ to each Jk segment are required for establishing this epigenetic topology and subsequent local gene recombination.
Heat-responsive dynamic shifts in alternative splicing of the coralAcropora cervicornis
Authors: Stankiewicz Kathryn H. , Valenzuela Jacob J. , Turkarslan Serdar , Wu Wei-Ju , Gomez-Campo Kelly , Locatelli Nicolas S. , Conn Trinity L. , Radice Veronica Z. , Parker Katherine E. , Alderdice Rachel , Bay Line K. , Voolstra Christian R. , Barshis Daniel J. , Baums Iliana B. , Baliga Nitin S. 
Published: January 2025

AbstractClimate change has caused drastic declines in corals. As sessile organisms, response to shifting environmental conditions may include changes in gene expression, epigenetic modifications, or the microbiome, but as of yet, a common mechanism of stress response, alternative splicing (AS), has been underexplored in corals. Using short-term acute thermal stress assays, we investigated patterns of AS in the scleractinian coralAcropora cervicornisduring response to and a subsequent overnight recovery phase from low (33℃), medium (35℃), and high (37℃) levels of heat stress. We find that 40% of the genomic gene set is subject to AS. Our findings demonstrate conserved and dynamic shifts in splicing profiles during the heat treatment and subsequent recovery phase. AS increased in response to heat stress and was primarily dominated by intron retention in specific classes of transcripts, including those related to splicing regulation itself. While AS returned to baseline levels post-exposure to low heat, AS persisted even after reprieve from higher levels of heat stress. Partial overlap of AS transcripts with differentially expressed genes suggests that AS may represent a distinct and previously underappreciated regulatory mechanism for thermal stress response in corals.
Method for costing a health system using a Health Systems Model
Authors: Mohan Sakshi , Mangal Tara D. , Manthalu Gerald , Mfutso-Bengo Joseph , Molaro Margherita , Nkhoma Dominic , She Bingling , Tafesse Wiktoria , Twea Pakwanja Desiree , Walker Simon , Chalkley Martin , Colbourn Tim , Hallett Timothy B. , Phillips Andrew , Revill Paul 
Published: January 2025

AbstractObjectivesModelling approaches that consider system-wide delivery platforms rather than single diseases are increasingly recognized as crucial for the economic evaluation of policy and investment choices and can be instrumental in forward-looking policy formulation. This paper develops a costing approach tailored to one such model, the Thanzi La Onse (TLO) model of Malawi’s healthcare system, to estimate healthcare delivery costs under varying health system assumptions.MethodsWe developed a mixed-method costing approach to estimate the total cost of healthcare delivery in Malawi using the TLO model, from a healthcare provider perspective. Through an iterative adjustment of key costing parameters, we attempted to align our model-based estimates with real-world expenditure and budget data. Costs were estimated over an 8-year period (2023–2030) under alternative scenarios of health system capacity, including supply chain performance and the size of the health workforce.ResultsA detailed comparison of our cost estimates against expenditure and budget data demonstrates the reliability of our costing method and assumptions, for the conditions and resources captured by the model. Under current health system capacity, the total cost of healthcare delivery in Malawi between 2023 and 2030 was estimated at $1.53 billion [95% confidence interval, $1.51b -$1.54b], which translates to an average annual cost of $309.83 million [$306.17m -$313.56m]. The estimation of costs under alternative scenarios demonstrates the importance of capturing feedback effects to correctly forecast healthcare costs.ConclusionMixed-method costing used within health system models, such as TLO, is a feasible and robust method for estimating healthcare delivery costs. This approach can provide valuable insights for health sector planning and resource allocation.
Anti-racism in postgraduate medical curricula
Authors: Sharma Chetna , Nacer Hadjer , Koay Aaron , McKee Martin , Devakumar Delan 
Published: January 2025

AbstractRacism is a public health threat and is firmly ingrained in the healthcare system. The reasons for this are complex as racism is rooted in historical, political, economic and social structures of society. To improve the health of their patients and the public, doctors must be able to recognise, name and act on the impact of racism. This study aims to understand action taken by postgraduate medical organisations in the UK in the aftermath of the global public reckoning of structural racism and its longstanding impacts on societal health in 2020. We analysed the public statements made by postgraduate medical organisations and then how this relates to the learning outcomes that doctors in training need to complete. We found that while many institutions (n=14) issued public commitments to anti-racism, reviewing the content of all GMC-approved postgraduate curricula (n=102) shows that the majority of UK doctors are receiving minimal or no education or training in anti-racism. As such, we call institutions involved in postgraduate medical education to include anti-racism competencies in medical curricula to support doctors to develop the skills, behaviours and knowledge to name and address the role of racism in health inequalities.
Recent Advances in the Diagnosis of Autoimmune Inner Ear Disease: A Scoping Review
Authors: Liu Jialin , Wang Changyu , Liu Siru 
Published: January 2025

AbstractAutoimmune inner ear disease (AIED) is a rare cause of sensorineural hearing loss, typically characterized by progressive bilateral hearing loss and vestibular symptoms. Diagnosing AIED is challenging due to the lack of specific biomarkers and its overlapping clinical features with other causes of hearing loss. This scoping review examines the recent advancements in the diagnostic approaches for AIED from 2020 to 2024, focusing on studies indexed in SCI, MEDLINE, and INSPEC. The review highlights progress in laboratory tests, imaging techniques, and genetic assessments, and discusses the implications of these advances in improving early diagnosis and treatment outcomes.
A scoping review protocol examining the application of large language models in healthcare education and public health learning spaces
Authors: Ndukwe Henry , Otukpa Emmanuel 
Published: January 2025

AbstractObjectiveThrough this scoping review, we aim to explore and synthesize existing knowledge and evidence on the learning approaches for incorporating LLMs into healthcare education and public health learning spaces. Specifically, we will attempt to investigate methods for auditing prompts for accuracy; tailoring prompts to improve task-specific accuracy and utility; and exploring how end-user feedback is used to refine and optimize LLM prompts over time. This review will provide a comprehensive understanding of how LLMs are being tailored and improved in these fields, contributing to the development of evidence-based strategies for their implementation. It will also identify areas for future research and innovation.IntroductionThe increasing integration of large language models (LLMs) into healthcare and public health practice and research highlights their potential to revolutionize service delivery, decision-making, and patient care. Despite these advancements, understanding how LLMs can be effectively tailored, audited, and refined for healthcare-specific tasks remains a critical area of inquiry. Key issues include, the accuracy of generated information, and their relevance to the medical and public health fields.Inclusion criteriaInclusion criteria will focus on studies addressing LLM applications in healthcare and public health, prompt engineering techniques, prompt auditing methods, and processes geared towards integrating user feedback. Articles that do not focus on healthcare or public health contexts and lack relevance to LLM learning approaches will be excluded.MethodsThe review is guided by the JBI methodology for scoping reviews complemented by updates from Levac et al. Databases including PubMed, Scopus, IEEE Xplore, and Web of Science will be searched for peer-reviewed articles, conference proceedings, and grey literature published in English and French from 2015 to 2025. Data extraction will include information on study characteristics, LLM models, prompt engineering strategies, auditing methodologies, and user feedback mechanisms. We will synthesize to identify trends, gaps, and best practices in leveraging LLMs to generate baseline data for auditing prompts that optimize AI learning and education needs in the healthcare and public health sector.