bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-scale cellular GUIDE-seq-2 and biochemical CHANGE-seq-R profiles reveal human genetic variation frequently affects Cas9 off-target activity
Authors: Lazzarotto Cicera R. , Li Yichao , Flory Ashley R. , Chyr Jacqueline , Yang Muyu , Katta Varun , Urbina Elizabeth , Lee GaHyun , Wood Rachael , Matsubara Azusa , Rashkin Sara R. , Ma Jian , Cheng Yong , Tsai Shengdar Q. 
Published: February 2025

AbstractGenome editing enzymes can introduce targeted changes to the DNA in living cells1–4, transforming biological research and enabling the first approved gene editing therapy for sickle cell disease5. However, their genome-wide activity can be altered by genetic variation at on- or off-target sites6–8, potentially impacting both their precision and therapeutic safety. Due to a lack of scalable methods to measure genome-wide editing activity in cells from large populations and diverse target libraries, the frequency and extent of these variant effects on editing remains unknown. Here, we present the first population-scale study of how genetic variation affects the cellular genome-wide activity of CRISPR-Cas9, enabled by a novel, sensitive, and unbiased cellular assay, GUIDE-seq-2 with improved scalability and accuracy compared to the original broadly adopted method9. Analyzing Cas9 genome-wide activity at 1,115 on- and off-target sites across six guide RNAs in cells from 95 individuals spanning four genetically diverse populations, we found that variants frequently overlap off-target sites, with 13% significantly altering Cas9 editing activity by up to 33% indels. To understand common features of high-impact variants, we developed a new massively parallel biochemical assay, CHANGE-seq-R, to measure Cas9 activity across millions of mismatched target sites, and trained a deep neural network model, CHANGE-net, to accurately predict and interpret the effects of single-nucleotide variants on off-targets with up to six mismatches. Taken together, our findings illuminate a path to account for genetic variation when designing genome editing strategies for research and therapeutics.
Merkel cell polyomavirus infection and persistence modelled in skin organoids
Authors: Albertini Silvia , Czech-Sioli Manja , Günther Thomas , Virdi Sanamjeet , Blümke Patrick , Röpke Lisann , Brinschwitz Veronika , Dandri Maura , Allweiss Lena , Reimer Rudolf , Schneider Carola , Hansen Arne , Krasemann Susanne , Wyler Emanuel , Landthaler Markus , Grundhoff Adam , Fischer Nicole 
Published: February 2025

AbstractMerkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCC). The virus is one of the few known human tumor viruses, and due to its direct role in this skin cancer development, it is a bona fide model for viral tumorigenesis and tumorigenesis in general. Chronic viruses in humans such as MCPyV are highly adapted to their host and current models to study infection, persistence and pathogenesis are highly limited. We here use an induced pluripotent stem cell (iPSC)-derived hair-bearing skin organoid (SkO) system to demonstrate efficient viral infection, progression and spread of MCPyV. Using bulk-, single cell - and spatial-transcriptomics, combined with immunostaining and nucleic acid hybridization technologies, we show that MCPyV ensures persistence due to a quasi-latency state within the majority of dermal fibroblasts carry the viral genome. Further, we identify the cell type of productive infection with papillary fibroblasts and dermal sheath fibroblasts supporting viral replication and progeny production. Our high-resolution methods demonstrate that the virus in these cells evades the innate immune response, as evidenced by the efficacy of interferon-beta treatment or ruxolitinib, a JAK/STAT inhibitor, in suppressing or stimulating viral replication. We show that iPSC-derived SkOs are able to support infection and long-term persistence of the virus under conditions very similar to those found in humans. Thus, this infection model provides a robust platform for understanding and characterizing the interaction of this virus with the immune system in infection, testing treatment strategies to control reactivation and map processes involved in tumor development.
Do lifestyle factors affect Patient-RepOrted clinical outcomes after total Knee replacement surgery? A feasibility cohort study (PRO-Knee)
Authors: Stephens Gareth , Liloglou Triantafyllos , Moffatt Maria , Littlewood Chris 
Published: February 2025

AbstractAimsTo evaluate the feasibility of a substantive cohort study to determine whether modifiable lifestyle factors, including smoking, physical inactivity, alcohol consumption and being overweight, affect patient-reported clinical outcomes after total knee replacement surgery.MethodsAdults awaiting total knee replacement surgery were recruited pre-operatively and completed self-reported questionnaires at baseline and 3- and 6-months post-surgery. Feasibility outcomes, including recruitment, retention and response rate of the primary outcome questionnaire were analysed descriptively.Results40 participants were recruited from 183 eligible patients (22%). 87.5% (35/40) participants returned questionnaires at 6-months. 85% (34/40) of participants were overweight (BMI>24.9), 25% (10/40) drank alcohol (AUDIT-C > 4), 5% (2/40) smoked tobacco and 67.5% (27/40) were physically inactive (GPAQ classification of ‘moderately inactive’, or ‘inactive’).ConclusionModifiable lifestyle factors including smoking, alcohol use, physical inactivity and being overweight are highly prevalent in patients waiting for total knee replacement. Based on this study, a future substantive cohort study investigating the effect of lifestyle factors on clinical outcomes post total knee replacement in the UK NHS is feasible.
Genetic data and meteorological conditions: unravelling the windborne transmission of H5N1 high-pathogenicity avian influenza between commercial poultry outbreaks
Authors: Nagy Alexander , Černíková Lenka , Sedlák Kamil 
Published: February 2025

AbstractUnderstanding the transmission routes of high-pathogenicity avian influenza (HPAI) is crucial for developing effective control measures to prevent its spread. In this context, windborne transmission, the idea that the virus can travel through the air over considerable distances, is a contentious concept and, documented cases are rare. Here, though, we provide genetic evidence supporting the feasibility of windborne transmission. During the 2023-24 HPAI season, molecular surveillance identified identical H5N1 strains among a cluster of unrelated commercial farms about 8 km apart in the Czech Republic. The episode started with the abrupt mortality of fattening ducks on one farm and was followed by disease outbreaks at two nearby high-biosecurity chicken farms. Using genetic, epizootiological, meteorological and geographical data, we reconstructed a mosaic of events strongly suggesting wind was the mechanism of infection transmission between poultry in at least two independent cases. By aligning the genetic and meteorological data with critical outbreak events, we determined the most likely time window during which the transmission occurred and inferred the sequence of infected houses at the recipient sites. Our results suggest that the contaminated plume emitted from the infected fattening duck farm was the critical medium of HPAI transmission, rather than the dust generated during depopulation. Furthermore, they also strongly implicate the role of confined mechanically-ventilated buildings with high population densities in facilitating windborne transmission and propagating virus concentrations below the minimum infectious dose at the recipient sites. These findings underscore the importance of considering windborne spread in future outbreak mitigation strategies.
Temperature-dependence of Early Development of Zebrafish and the Consequences for Laboratory Use and Animal Welfare
Authors: Miller Angelina , Schröder Katja Lisa , Braun Karsten Eike , Steindorf Caitlin , Ottermanns Richard , Roß-Nickoll Martina , Hollert Henner , Backhaus Thomas 
Published: February 2025

AbstractZebrafish (Danio rerio) is widely used as a model organism in biological research. However, the impact of different incubation temperatures on specific developmental endpoints is still insufficiently studied.This study quantifies developmental differences of zebrafish embryos incubated at two commonly used temperatures (26 °C and 28 °C), focusing on key developmental endpoints (onset of heartbeat, hatching time, eye size, yolk sac consumption, body length). For this purpose, we recorded a high-resolution time series comprising hourly observations of early developmental stages and key events and bi-hourly observations of body length until 120 hours post fertilization. Additionally, we recorded a low-resolution time series at 72, 96, and 119 hours post fertilization for detailed measurements of eye size, yolk sac area, and swim bladder size.Embryos incubated at 26 °C consistently exhibited delays in reaching developmental stages compared to those reared at 28 °C. Significant differences were apparent from the earliest stages of development, with the delays becoming more pronounced as the embryos progressed to more complex stages. Yolk sac consumption was delayed by approximately 10 hours at 26 °C by 120 hours post fertilization, indicating a delayed onset of independent feeding. These data suggest that exclusively time-based regulatory limits for rearing zebrafish eleutheroembryos, such as the 120 hours post fertilization threshold commonly interpreted from the German regulation TierSchVerV (Tierschutz-Versuchstierverordnung), do not adequately account for the temperature-dependency of zebrafish development.The results highlight the need for guidelines that link incubation temperatures to developmental progress.
Behavioral reasoning in technological adoption: consumer response to early-stage radical innovations
Authors: Sharma Anshu , Gandhi Aradhana Vikas 
Published: February 2025

Purpose
Despite a sizeable body of innovation adoption scholarship, innovation failure rates are estimated to be in the range of 40% to 80%. This study aims to better explain the complex consumer decision-making journey by leveraging behavioral reasoning theory (BRT) and integrating the dichotomous influences of reasons for (RF) and reasons against (RA), and the role of moderators in a unified behavioral framework.

Design/methodology/approach
First, an exploratory reason elicitation study was conducted (n = 44) to propose a theoretical model with contextual reasons for and against constructs. Second, a quantitative study was conducted (n = 400) to validate the hypothesized structural relationships and the role of moderators.

Findings
Reasons for and against adoption are discrete constructs and significantly impact consumer attitudes and intentions. Reasons for adoption emerge as the strongest influencing factor in shaping consumer attitudes. Values influence intentions directly and via reasons but do not influence attitudes. Consumer innovativeness and external stressors moderate consumers’ resistance toward adopting innovations.

Practical implications
This study presents a novel approach for managers to generate deeper insights into consumer decision-making by integrating contextual reasons for and against, as well as the role of moderators in a unified behavioral framework. This approach enables managers to address both drivers and inhibitors of adoption in the specific radical innovation context they are working on.

Originality/value
This study integrates reasons for and against in a unified behavioral framework and applies it to radical technological innovations in an emerging market context. This study introduces novel constructs to BRT and examines the role of moderators in the BRT framework.
The Ghost Dance and Wounded Knee: teaching spiritual resistance to colonialism
Authors: Corrigan Sean 
Published: February 2025

PurposeThis article uses Tribal Critical Race Theory (TribalCrit) and human rights education (HRE) to frame social studies instruction about the Ghost Dance movement of the late 1800s. This religious ritual served as a source of spiritual communion for Native Americans across the Western United States during an especially brutal era of colonization, most tragically exemplified by the Wounded Knee Massacre. The critical approaches offered are meant to challenge dominant narratives that often neglect or minimize colonialism and White supremacy.Design/methodology/approachTribalCrit is useful in framing acts of racism and genocide faced by Indigenous people in American history and can help teachers approach issues of social justice in a way that identifies oppression, while also promoting empathy and advocacy (Brayboy, 2005; Sabzalian et al., 2021). Furthermore, human rights concepts can support a critical interrogation of colonialism by providing a framework that guides analysis of multidimensional oppression (Bajaj, 2011).FindingsThe pedagogical approaches included in this article link the historical context of these events to tenets of TribalCrit and HRE. These strategies are explicitly connected to the National Curriculum Standards for Social Studies and the C3 Framework. A lesson plan and enrichment sources, linked to the C3 Inquiry Design Model, are provided.Originality/valueThe Ghost Dance is a powerful illustration of spiritual resistance to colonial policies and ideologies in the United States, such as the Dawes Act and Christian nationalism. An examination of this important religious movement through the critical lenses offered here may build empathy, support justice-oriented citizenship and decolonize curriculum.
The effectiveness of an auditory integration‐based developmental support programme on the sensory development and self‐regulation skills of autistic children in Turkey
Authors: Cetin‐Sultanoglu Saliha , Aral Neriman 
Published: February 2025

AbstractThis study examines the impact of an auditory integration‐based developmental support programme on the sensory development and self‐regulation skills of children with autism aged three to five years in Turkey. This mixed‐methodology research combined quantitative and qualitative methods, and data were collected using a general information form, the individual needs determination form, the adapted autism behaviour checklist (ABC), the Gilliam autism rating scale‐2‐Turkish version (GARS‐2‐T), the sense and self‐regulation checklist (SSC) and semi‐structured interviews. An AB model was used to determine the effectiveness of the auditory integration programme in supporting the sensory and self‐regulation skills of children with autism. The quantitative data were graphically analysed, while the qualitative data underwent content analysis. The findings establish that the children's final evaluation results were lower than their initial assessments, signifying that the intervention had a positive impact. The qualitative data obtained from interviews with the participating children's mothers concurred with the quantitative results, and the mothers expressed favourable views regarding the programme.
Is Survival Impacted by One or Several Successive Cancers After Liver Transplantation? A French National Study
Authors: Briant Anaïs R. , Morello Rémy , Sérée Olivier , Vigneron Nicolas , Wilson Sarah , Besch Camille , Houssel‐Debry Pauline , Pageaux Georges‐Philippe , Coilly Audrey , Dumortier Jérôme , Altieri Mario 
Published: February 2025

ABSTRACTBackground and AimDe novo cancers after liver transplantation (LT) are major causes of complications and mortality after LT. No report was found in the literature on several successive cancers (SSC). The aim of this study was to see if the survival of one or more cancers was different and to study the survival prognostic factors of patients with one cancer or SSC after LT.MethodsUsing data from the French national database, 114 French patients who underwent LT between 1993 and 2012 were followed up until their death or until June 2016. The Cox model performed to analyze potential risk factors (cancer characteristics, immunosuppressive therapy (IT), smoking, and alcohol use).ResultsAfter an average follow‐up of 9.8 ± 5.1 years, 52 patients developed 1 cancer, 49 had 2 cancers, and 13 had 3 cancers. The reduction in survival time was significantly and independently associated with the metastatic stage (hazard ratio (HR) = 3.98, 95% confidence interval (95% CI) = [1.45–10.93], p < 0.001), ENT (otolaryngology), and respiratory cancer versus genitourinary (HR = 8.28, 95% CI = [3.12–22.02], p < 0.001), and SSC (HR = 2.54, 95% CI = [1.39–4.65], p = 0.014).ConclusionThe patients with ENT, respiratory cancers have a shorter survival. The stage of cancer and SSC reduces median survival at 10 years. The earliness of the first cancer should be taken as a warning signal of risk of SSC and impaired survival.
Artificial Intelligence Literacy Levels of Perioperative Nurses: The Case of Türkiye
Authors: Kahraman Hilal , Akutay Seda , Yüceler Kaçmaz Hatice , Taşci Sultan 
Published: February 2025

ABSTRACTArtificial intelligence (AI) experience among nurses in perioperative settings is crucial for effective healthcare delivery. This study aimed to assess AI literacy levels and associated characteristics among perioperative nurses in Türkiye. This cross‐sectional study was conducted between March 15 and April 15, 2024, and included 505 perioperative nurses. Data were collected online using the “Nurse Information Form” and “AI Literacy Scale.” Snowball sampling technique was used to enlist individuals. The mean literacy score was 44.35 ± 5.88, which means moderate proficiency. Key elements associated with high literacy levels included being male, familiarity with and use of AI applications, youth, seeing AI as a tool to alleviate workload, and using information technology tools. The results show that although perioperative nurses have a moderate level of AI literacy, their use of AI tools is minimal. The findings underline the need for professional development in AI integration and the inclusion of relevant materials in nursing education programs.
The PopbZIP2‐PopMYB4 regulatory module enhances disease resistance in poplars by modulating proanthocyanidin accumulation
Authors: Tan Shuxian , Chen Sisi , Zhang Haoyu , Si Jingna , Wang Haofei , Wang Tong , Zhang Xiang , Wang Yue , Wu Jiadong , Zhang Deqiang , Bao Fei , Xie Jianbo 
Published: February 2025

Summary
Anthracnose, caused by Colletotrichum gloeosporioides, is a significant fungal disease that affects poplar trees globally, leading to reduced yields and substantial economic losses. Proanthocyanidins (PAs) play a key role in resistance to fungal pathogens; however, the mechanisms by which PAs mediate resistance to anthracnose in poplar remain poorly understood.
In this study, we identified PopbZIP2, a transcription factor‐encoding gene that was initially expressed in infected leaves and subsequently in uninfected leaves in response to C. gloeosporioides infection. As a transcriptional activator, PopbZIP2 can bind to the promoters of target genes PopGRF3 and PopAPA1, increasing proanthocyanidin levels in cells to enhance defense against pathogens. It is noteworthy that the PopAPA1 protein can directly inhibit pathogen growth.
We further demonstrated that PopMYB4 can interact with PopbZIP2, reducing its promoter binding activity and thereby inhibiting the expression of PopGRF3 and PopAPA1. Overexpression of PopMYB4 led to sensitivity to the pathogen C. gloeosporiodes. Under normal conditions, the soluble and insoluble proanthocyanidin contents in PopMYB4 transgenic plants were significantly lower compared to the control.
The dual regulation of immune responses by the PopMYB4‐PopbZIP2 module unveils a novel regulatory mechanism in Populus, enhancing our understanding of the complex networks governing immune responses.
Fabrication and characterization of metallic glass nanowire-anchored microfluidic channels
Authors: Theeda Sumanth , Kumar Golden 
Published: February 2025

Abstract
Nanowire-based microfluidic devices combine the strengths of microfluidics and nanostructures for applications in cell biology and chemical sensing. However, their use has been limited by the complexity of the fabrication methods. In this study, we present a simple approach for fabricating and integrating metallic glass nanowires into microfluidic channels. Metallic glass nanowires were formed by thermoplastic drawing on a silicon substrate. The silicon-anchored nanowire array was sealed with a PDMS channel to create a nanowire-integrated microfluidic device. The effect of nanowire geometry on the flow rate was characterized. The experimental results were compared with CFD simulations to understand the fluid-nanowire interaction. The potential of surface modification to functionalize the metallic glass nanowires was evaluated.
Enrichment of solar heat exchanger thermal performance by the integration of beeswax and hybrid nanofluid (ZnO/MgO)
Authors: Venkatesh R. , M. Soudagar Manzoore Elahi , Sharma Aman , Naga Bhooshanam N , Vinayagam Mohanavel , M Ravichandran , A. Alotaibi Majed 
Published: February 2025

Abstract
Solar energy has the potential to be used for energy applications. However, its thermal performance can be affected by weather conditions, changes in solar radiation, and cloudy days. This study aims to resolve the mentioned disagreement and improve the solar thermal performance of flat plate solar collectors (FPC) that use beeswax phase change material and a hybrid nanofluid made up of (50:50) zinc oxide (ZnO) and magnesium oxide (MgO) at a concentration of 1-3 volume, operated at 2 litres per minute (LPM). The different volume concentrations include hybrid nanofluid (ZnO/MgO) at 1 vol%, PCM mixed with hybrid nanofluid (ZnO/MgO) at 2 vol%, and PCM combined with hybrid nanofluid (ZnO/MgO) at 3 vol%. The hybrid nanofluid that results has an improved heat transfer rate, reduced heat loss, greater latent heat storage, and better thermal and exergy efficiency than water. The hybrid nanofluid (ZnO/MgO) at a concentration of 3 vol% has the highest thermal conductivity, reaching around 0.93 W/mK. It also has an outlet temperature of 91.5°C, a heat transfer rate of approximately 398.4 W, and a latent heat storage capacity of about 389.1 KJ/kg. Additionally, the typical thermal efficiency is around 68.6%, while the average exergy efficiency is about 30.1%.