bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the consequences of chronic short sleep for metabolism and survival of oxidative stress
Authors: Tener Samantha J. , Kim Chloe E. , Lee Jungwon , Oraedu Kairaluchi , Gatto Jared A. , Chang Timothy Y. , Lam Carly , Schanta Ryan , Jankowski Meaghan S. , Park Scarlet J. , Hurley Jennifer M. , Ulgherait Matthew , Canman Julie C. , Ja William W. , Collins Douglas B. , Shirasu-Hiza Mimi 
Published: December 2024

ABSTRACTIn previous work, we found that short sleep caused sensitivity to oxidative stress; here we set out to characterize the physiological state of a diverse group of chronically short-sleeping mutants during hyperoxia as an acute oxidative stress. Using RNA-sequencing analysis, we found that short-sleeping mutants had a normal transcriptional oxidative stress response relative to controls. In both short-sleeping mutants and controls, hyperoxia led to downregulation of glycolytic genes and upregulation of genes involved in fatty acid metabolism, reminiscent of metabolic shifts during sleep. We hypothesized that short-sleeping mutants may be sensitive to hyperoxia because of defects in metabolism. Consistent with this, short-sleeping mutants were sensitive to starvation. Using metabolomics, we identified a pattern of low levels of long chain fatty acids and lysophospholipids in short-sleeping mutants relative to controls during hyperoxia, suggesting a defect in lipid metabolism. Though short-sleeping mutants did not have common defects in many aspects of lipid metabolism (basal fat stores, usage kinetics during hyperoxia, respiration rates, and cuticular hydrocarbon profiles), they were all sensitive to dehydration, suggesting a general defect in cuticular hydrocarbons, which protect against dehydration. To test the bi-directionality of sleep and lipid metabolism, we tested flies with both diet-induced obesity and genetic obesity. Flies with diet-induced obesity had no sleep or oxidative stress phenotype; in contrast, the lipid metabolic mutant,brummer, slept significantly more than controls but was sensitive to oxidative stress. Previously, all short sleepers tested were sensitive and all long sleepers resistant to oxidative stress.brummermutants, the first exceptions to this rule, lack a key enzyme required to mobilize fat stores, suggesting that a defect in accessing lipid stores can cause sensitivity to oxidative stress. Taken together, we found that short-sleeping mutants have many phenotypes in common: sensitivity to oxidative stress, starvation, dehydration, and defects in lipid metabolites. These results argue against a specific role for sleep as an antioxidant and suggest the possibility that lipid metabolic defects underlie the sensitivity to oxidative stress of short-sleeping mutants.
Multidimensional variable dose analysis (mVDA) is a novel method for high-throughput mapping of genetic interactions
Authors: Sengupta S. , Housden B.E. 
Published: December 2024

ABSTRACTThe mapping of genetic interactions is a powerful tool to determine gene functions, assemble the structures of biological pathways and to identify therapeutic targets for disease. However, while there have been significant advances in the screening techniques used to identify genetic interactions over the past decade, methods that are sufficiently scalable to test genetic interactions on a genome level are still far from our current capabilities. Here, we describe an approach to genetic interaction screening inDrosophilacells that overcomes the scaling issues associated with most other methods. This method, called multidimensional Variable Dose Analysis (mVDA), allows multiple, random genes to be inhibited within each cell of a mixed population and the relative phenotypes caused by each gene or pair of genes to be deconvoluted. This means that reagent library size and cell population size do not scale exponentially with the number of genes to be tested, unlike previous methods. This method therefore has the potential to allow genome wide mapping of genetic interactions inDrosophilacells for the first time.
Monitoring for fisheries or for fish? Declines in monitoring of salmon spawners continue despite a conservation crisis
Authors: Atkinson Emma M. , Carturan Bruno S. , Atkinson Clare P. , Bateman Andrew W. , Connors Katrina , Hertz Eric , Peacock Stephanie J. 
Published: December 2024

AbstractMonitoring of salmon in Pacific Canada has been declining for decades. Spawner timeseries enable researchers to quantify impacts of local stressors, identify when and where management interventions are required to avoid extirpations, and evaluate the efficacy of recovery efforts. These data are more important now than ever, as uniquely adapted spawning populations underlie salmon resilience and their ability to adapt to climate change, and fine-scale data can inform terminal fisheries being revitalized by First Nations. We revisit the state of spawner data from the Yukon to southern BC. Almost two-thirds of salmon populations that were historically monitored have no reported estimates in 2013-2022 – the worst decade for data since monitoring programs began in the 1950s. We found strong correlations between the number of populations monitored and catch for each species, suggesting that monitoring is primarily motivated by commercial fisheries management. We recommend clarifying monitoring objectives and strategic investments to improve monitoring outcomes for salmon and communities. We emphasize data stewardship, as ensuring access to these baseline data is a cornerstone for rebuilding wild Pacific salmon.
An Investigation into Mechanomyography for Signal Extraction and Classification of Human Lower Limb Activity
Authors: Bai Yu , Guan Xiao Rong , Zhang Rui , Cheng Shi , Wang zheng 
Published: December 2024

AbstractTo mitigate the difficulties associated with the extraction of Mechanomyography (MMG) signals from raw Accelerometer (ACC) data and the subsequent classification of human lower limb activities based on MMG signals, the Feature Mode Decomposition (FMD) algorithm has been utilized for the isolation of the MMG signal. Simultaneously, surface Electromyography (sEMG) signals were recorded to perform correlation analyses, thereby validating the effectiveness of the extracted Mechanomyography (MMG) signals. The results demonstrate that the envelope entropy derived from the FMD was the lowest among the observed values, and the composite signal obtained via FMD displayed the highest correlation with the sEMG signal. This indicates that FMD is capable of efficiently isolating the MMG signal while maintaining the maximal quantity of muscle contraction data. To address the challenge of classifying human lower limb activities, a comprehensive feature extraction procedure was implemented, resulting in the derivation of 448 unique features from multi-channel mechanomyography (MMG) signals. Subsequently, Kernel Principal Component Analysis (KPCA) was employed to diminish the feature set’s dimensionality. This was succeeded by the deployment of a Temporal Convolutional Network integrated with an Attention mechanism (TCN-Attention) to train the classification model. Additionally, an enhanced Northern Goshawk Optimization Algorithm was leveraged for optimization purposes. The findings indicate that FMD exhibited the minimum envelope entropy value of 8.13, concurrently attaining the maximum correlation coefficient of 0.87 between MMG and sEMG signals. Significantly, the SCNGO-TCN-Attention model demonstrated superior classification accuracy, attaining an exceptional accuracy rate of 98.44%.
Multi-omic profiling identifies malignant subpopulations and a hypoxia-driven angiogenic axis as therapeutic vulnerabilities in sinonasal squamous cell carcinoma
Authors: You Chaelin , Park Jaewoo , Jang Jung Yeon , Yu Myeong Sang , Chung Yoo-Sam , Kang Keunsoo , Park Jihwan , Kim Ji Heui , Kang Kyuho 
Published: December 2024

AbstractSinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with limited treatment options, necessitating comprehensive molecular characterization to uncover actionable therapeutic targets. Here, we integrate bulk and single-cell transcriptomics, epigenomics, and DNA methylation profiling to construct a detailed molecular and cellular landscape of SNSCC. Our analysis identifies five transcriptionally and epigenetically distinct malignant subpopulations, including hypoxic (TC1) and proliferative (TC2) clusters, with TC1 showing significant association with poor clinical outcomes. We uncover a hypoxia-driven angiogenic axis, wherein TC1 cells secrete adrenomedullin (ADM), MIF, and VEGFA to activate endothelial tip cells, fostering tumor angiogenesis. Epigenetic reprogramming, characterized by alterations in DNA methylation and chromatin accessibility, underpins these transcriptional programs, with AP-1 transcription factors emerging as key regulators. Notably, ADM expression is epigenetically controlled, correlates with advanced clinical stage, and predicts reduced survival in head and neck cancer patients. This multi-omic study highlights the tumor heterogeneity and microenvironmental interactions driving SNSCC progression, revealing epigenetically regulated pathways as promising therapeutic targets for future intervention.
MOZ and HBO1 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets inNUP98-Rearranged Acute Myeloid Leukemia
Authors: Michmerhuizen Nicole L. , Heikamp Emily B. , Iacobucci Ilaria , Umeda Masayuki , Arthur Bright , Mishra Vibhor , Di Giacomo Danika , Hiltenbrand Ryan , Gao Qingsong , Radko-Juettner Sandi , Lott Josi , Martucci Cynthia , Subramanyam Varsha , Hatton Charlie , Baviskar Pradyuamna , Portola Pablo , Claquin Aurelie , Chandra Bappaditya , Baggett David W. , Khalighifar Ali , Huang Hongling , Zhou Peipei , Long Lingyun , Shi Hao , Sun Yu , Papachristou Evangelia K. , Chilamakuri Chandra Sekhar Reddy , Vitorino Francisca N. de L. , Gongora Joanna M. , Janke Laura , Kentsis Alex , D’Santos Clive S. , Garcia Benjamin A. , Kriwacki Richard W. , Chi Hongbo , Klco Jeffery M. , Armstrong Scott A. , Mullighan Charles G. 
Published: December 2024

ABSTRACTNUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML) and drive leukemogenesis through liquid-liquid phase separation-mediated nuclear condensate formation. However, the composition and consequences of NUP98 FO-associated condensates are incompletely understood. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including MOZ/KAT6A, HBO1/KAT7, and the common MOZ/HBO1 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies inNUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition ofMozandHbo1impairsNUP98-r cell fitness. MOZ/HBO1 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at theMeis1locus, and led to myeloid cell differentiation. Additionally, MOZ/HBO1 inhibition decreased leukemic burden in multipleNUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies inNUP98-r AML.SIGNIFICANCE STATEMENTMOZ and HBO1 associate with NUP98 fusion oncoprotein condensates to drive leukemogenesis. Inhibition of their histone acetyltransferase activity is an effective therapeutic strategy inNUP98-rearranged leukemias, including those resistant to Menin inhibition. Moreover, combined MOZ/HBO1 and Menin inhibition is synergistic, supporting clinical translation to improve outcomes of NUP98 FO-driven leukemias.
Do morphologically distinct groups correspond to reproductively isolated species? A case study inMyrmicaants from Switzerland
Authors: Lavanchy Guillaume , Galkowski Christophe , Jecha Kristine , Freitag Anne , Avril Amaury , Dépraz Aline , Schwander Tanja 
Published: December 2024

AbstractThe most widely used definition of a species is that it is reproductively isolated from other populations. Yet, most species are described on the basis of morphological criteria, and reproductive isolation is seldom tested. Using the ant genusMyrmicaLatreille (Hymenoptera, Formicidae) as a model, we ask whether species described as distinct based on (often subtle) morphological differences indeed form reproductively isolated lineages. We collected and morphologically identified 918Myrmicaants from a 3212 km2area in Switzerland. We then combined DNA barcoding (based on COI) and RAD sequencing to identify genetically isolated lineages. Out of the 14 morphological species identified, 13 formed genetically differentiated lineages, while the last one was not supported by our genetic data. Overall, the morphological identification was congruent with genetic lineage delineation for 94.9% of individuals. Our dataset also allowed us to screen for cryptic lineages in the five most frequent species, including inM. scabrinodiswhere cryptic lineages were previously suggested, but we found no evidence for cryptic species. Overall, our results indicate that morphology parallels genetic isolation in the studied species. However, an integrative approach combining morphological identification with nuclear marker genotyping is necessary for confident species identification of all individuals. Finally, our results provide a library of validated COI barcodes for futureMyrmicaspecimen identification.
RNA Binding of GAPDH Controls Transcript Stability and Protein Translation in Acute Myeloid Leukemia
Authors: Shamloo Sama , Schloßhauer Jeffrey L. , Tiwari Shashank , Fischer Kim Denise , Ghebrechristos Yohana , Kratzenberg Lisa , Bejoy Aathma Merin , Aifantis Ioannis , Wang Eric , Imig Jochen 
Published: December 2024

AbstractDysregulation of RNA binding proteins (RBPs) is a hallmark in cancerous cells. In acute myeloid leukemia (AML) RBPs are key regulators of tumor proliferation. While classical RBPs have defined RNA binding domains, RNA recognition and function in AML by non-canonical RBPs (ncRBPs) remain unclear. Given the inherent complexity of targeting AML broadly, our goal was to uncover potential ncRBP candidates critical for AML survival using a CRISPR/Cas-based screening. We identified the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a pro-proliferative factor in AML cells. Based on cross-linking and immunoprecipitation (CLIP), we are defining the global targetome, detecting novel RNA targets mainly located within 5’UTRs, including GAPDH, RPL13a, and PKM. The knockdown of GAPDH unveiled genetic pathways related to ribosome biogenesis, translation initiation, and regulation. Moreover, we demonstrated a stabilizing effect through GAPDH binding to target transcripts including its own mRNA. The present findings provide new insights on the RNA functions and characteristics of GAPDH in AML.
Designing a multi-serotype Dengue virus vaccine: anin silicoapproach to broad-spectrum immunity
Authors: Singh Ankita , Glushchenko Oksana , Ustiugova Alina , Alawi Khadija M , Korzinkin Mikhail , Zhavronkov Alex , Castiglione Filippo 
Published: December 2024

AbstractDengue virus infection represents a major global health issue, with four distinct serotypes complicating the challenge of developing a vaccine due to the need for balanced, long-lasting immunity against all serotypes. Current vaccines have limitations, including an increased risk of severe dengue in seronegative individuals and moderate efficacy, highlighting the need for more effective solutions. Our study aimed to design a multi-serotype Dengue virus vaccine using a computational approach to achieve broad-spectrum immunity. We employed advanced computational tools and algorithms to predict B-cell and T-cell epitopes, ensuring the selection of antigenic targets that provide comprehensive protection against all four serotypes. The methodology included tools for B-cell epitope prediction, tools for MHC class II and I peptide predictions, and tools for toxicity and allergenicity screening to ensure the safety of the vaccine candidates. Our results identified 21 B-cell epitopes, 15 CTL peptides, and 12 HTL peptides, validated for safety regarding toxicity and allergenic potential. The vaccine construct incorporated the adjuvant β-defensin-3 and specific linkers to enhance immunogenicity and stability. Tertiary structure prediction, Ramachandran plot analysis, and stereochemical examination confirmed the stability and quality of the vaccine model.These findings demonstrate the potential of computational methods in addressing the complex challenges of Dengue virus vaccine development. Our computational approach offers a novel pathway for vaccine design, potentially accelerating the development of effective multi-serotype vaccines. This study provides a promising foundation for future research and clinical validation, marking a significant step forward in dengue vaccine development.
ROSLT: An Improved Raspberry-Pi Open-Source Live Voluntary-Wheel Running Tracker Method and Resource
Authors: Sanosa Patrick , Marrow Jade P. , Malicki Amelia R. , Brunt Keith R. , Simpson Jeremy A. 
Published: December 2024

AbstractBackgroundExercise promotes health and has therapeutic effects on disease. Over time, the body improves its maximal exercise capacity through training adaptations such as an increase in VO2 max. In mice, voluntary wheel running allows for a natural setting to test spontaneous running behaviour under non-stressed conditions. There is a need to design sensitive animal-based assay that improves resolution for differentiating exercise performance from a regular cyclometer (which presents a single value from a summary of dynamic data collected over time) and offer circadian analyses. The purpose of this work is to examine the exercise behaviours of mice with a focus on circadian rhythm of running. We hypothesize the pi cyclometer (ROSLT) will mirror VDO M2.1 behaviors, enhancing circadian rhythm insights.MethodsUsing a hand-built cyclometer programmed through the Raspberry Pi computer, voluntary wheel running behaviours in CD-1 mice (∼8-10 weeks) were recorded for 6 consecutive days. This features a Hall Effect sensor and neodymium magnets attached on the running wheels that will detect changes to wheel rotation, speed, acceleration, and distance (continuously) and publish the data to a server in real-time. To compare capabilities, running wheels will also be equipped with the VDO M2.1 WR Cycling Computer to track distance which will be manually recorded once a day. Accuracy from both devices were mechanically validated.ResultsThe main findings include that voluntary wheel running distance over 6 days produces inaccuracies by the VDO. The VDO showed fluctuations in distance over the last 3 days, while ROSLT showed consistent measurements.ConclusionThis comparison shows that ROSLT expands on the running activity of mice each day while maintaining accuracy and precision. This novel dynamic circadian cyclometer will advance our research abilities and can be used in differentiating exercise performance in applications such as doping.
Navigating Medication Safety with Electronic Medical Records: Insights from a Dual-Phase Implementation in Paediatric, Neonatal and Maternity Care
Authors: Mordaunt Dylan A , Johnson Nichola , Verghese Santosh , Parker Rhys , Gibb Katy , Palmer Lyle J 
Published: December 2024

AbstractObjectiveEMR implementations can lead to changes in medication safety events due to the disruption of clinical activities by the implementation. The current study aimed to evaluate the impact of an Electronic Medical Record (EMR) implementation on medication safety events within women’s and children’s services of a large tertiary public hospital.MethodsThis Real-World Evidence (RWE) study utilised a differences-in-differences analysis with negative binomial regression to accommodate overdispersion in medication safety event counts. We compared change over time in key outcomes between areas where the EMR was activated and areas where it was not activated. Data were collected from January 2020 to February 2024 from the enterprise incident management system, spanning periods before and after two separate EMR system activations in 2021 and 2023.ResultsThere was an initial rise in minor and near-miss incidents immediately following activation, with no overall increase in events in groups not activated. The observed rise in incidents was in the time immediately around the activation and was not sustained over the longer term. There were no significant changes in trend over time.ConclusionsOur findings suggest that the implementation of the EMR system was not associated with a change in the occurrence of medication safety events over the longer term. Our study highlights the potential of EMR systems to be integrated into healthcare settings without worsening medication safety outcomes; implementation also doesn’t appear to have improved rates.
Nurses’ Fall Risk Judgements - Cognitive Biases and Contextual Factors Explaining Variability: A multi-centre cross-sectional study
Authors: Takase Miyuki , Kisanuki Naomi , Yoko Sato , Mitsunaka Kazue , Yamamoto Masako 
Published: December 2024

AbstractBackgroundAssessing fall risk is a complex process requiring the integration of diverse information and cognitive strategies. Despite this complexity, few studies have explored how nurses make these judgements. Moreover, existing research suggests variability in nurses’ fall risk assessments, but the reasons for this variation and its appropriateness remain unclear.ObjectiveThis study aimed to investigate how nurses judge fall risk, and the factors associated with their judgements.MethodsUsing purposive sampling, 335 nurses from six hospitals in western Japan participated in an online survey. The participants rated the likelihood of falls in 18 patient scenarios and completed measures of base-rate neglect, belief bias, and availability bias. A linear mixed-effects regression tree was used to identify factors related to their judgements, and a linear mixed-effects regression model examined associations between judgement variability, cognitive biases, and clinical specialty.ResultsNurses’ fall risk assessments were primarily influenced by whether patients called for assistance, followed by the use of sleeping pills, the presence of a tube or drain, and patient mobility status. Judgement variability was linked to nurses’ gender, education, clinical specialty, and susceptibility to availability bias.ConclusionVariability in clinical judgement may be justified when reflecting personalised, context-specific care. However, inconsistencies arising from cognitive biases are problematic. Healthcare organisations should offer targeted training to enhance contextual expertise and reduce the influence of cognitive biases on fall risk assessments.