bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Effect of Delay Phenomenon and Quercetin Application on the Viability of Dorsal Skin Island Flaps in Rats
Authors: Bi Kübra , Livaoğlu Murat 
Published: December 2024

Background
Surgical delay is any surgical intervention performed 7–14 days before flap elevation, separating part of flap from its vascular bed and aiming to decrease flap necrosis. However, delay surgery needs to be planned and performed as a separate surgical operation. Quercetin is a flavonoid with anti-inflammatory, and vasodilator effects. This study compares the effects of quercetin and surgical delay on flap survival.

Materials and Methods
The study included 32 male Wistar rats divided into four groups: control group (group 1), surgical delay group (group 2), quercetin group (group 3), and both surgical delay and quercetin group (group 4). All dorsal skin island flaps were elevated based on deep circumflex iliac artery and 7 days were selected as waiting period after flap elevation, 50 mg/kg (0.5 mL) intraperitoneal quercetin administration period, and surgical delay period. Macroscopically flap necrosis rates were calculated and histopathological examination was performed to evaluate number of vessels, vessel lumen diameters, inflammation, epidermal damage, and dermal fibrosis scores. All rats were euthanized.

Results
Flap necrosis rates, inflammation, epidermal damage, and dermal fibrosis scores of group 3 and 4 were found to be lower than group 1 and 2 (P < 0.05). Vascular lumen diameter of group 2, 3, and 4 were found to be higher than group 1 (P < 0.05) but no statistically significant difference was found for this parameter between group 2, 3, and 4 (P > 0.05). The number of vessels were found to be higher in group 2, group 3, and group 4 compared with group 1, but this difference was not to be found statistically significant (P = 0.534).

Conclusions
This study shows that quercetin application is more effective in reducing flap necrosis rates and anti-inflammatory effect than surgical delay and also has superior effect in terms of vasodilation.
Mapping the Void
Authors: Harris Chelsea A. , Vastardis Andrew , Jobin Chad , Dossett Lesly 
Published: December 2024

Objective:
To delineate how identity-based bias exposure evolves with rank and/or context among health care workers, and assess their attitudes toward existing diversity, equity, and inclusion (DEI) education.

Background:
Although DEI training is widely mandated for health care workers, few studies examine how clinicians’ needs evolve across a career, how context impacts recipients’ ability to respond, or how well existing programs adapt to individual contexts.

Methods:
A 54-question electronic survey was distributed during Morbidity and Mortality conferences beginning in December 2020. Descriptive statistics were performed regarding respondents’ bias exposure across rank, perceptions regarding existing training’s fidelity to recipients’ lived experience, and ability to confer useful response strategies.

Results:
This study included 648 individuals (65.6% White; 50.2% women) practicing in mostly academic medical centers (70.6%). Respondents affirmed that discrimination was common, with half (320, 49.4%) reporting that they experienced bias at least monthly. Among people of color, the proportion reporting monthly exposure decreased with rank. Women of color experienced the biggest drop (74% as residents/fellows down to 11% in late career). Broadly, participants reported the greatest discomfort in addressing subtle bias from patients or high-ranked individuals, and this did not uniformly improve with seniority. Finally, although 478 (73.8%) individuals reported receiving DEI training, 51.3% of respondents reported online DEI modules had little utility. Shortcomings included that training focused on individual rather than structural solutions and that it did not confer response strategies users could reliably employ.

Conclusions:
Identity and context strongly influence both clinicians’ exposure and ability to respond to bias in the hospital environment, independent of seniority. Existing DEI training fails to account for this nuance, ultimately diminishing its utility to clinicians.
A murine model of cardiovascular-kidney-metabolic syndrome demonstrates compromised limb function in the ischemic hind limb
Authors: Lotfollahzadeh Saran , Paul Herreet , Bonifacio Joshua , Almiron Ricardo , Hockestra Isaac , Prezkop Kylla , Yamamoto Trent , Piqueras Maria Carmen , Yin Wenqing , Malikova Marina , Siracuse Jeffrey J. , Belghasem Mostafa , Cabral Howard , Sayed Nazish , Chitalia Vipul 
Published: December 2024

AbstractsBackgroundCardiovascular-Kidney-metabolic (CKM) syndrome is a public health problem involving > 90% of the US and results in premature CVD at a relatively preserved GFR. The molecular mediators of CKM are poorly understood, partly due to the lack of a reliable animal model. We set out to generate an animal model with renal and metabolic dysfunctions, using PAD as a CKM manifestation.MethodsA group of C57BL/6 mice was randomized into four groups-a normal diet (ND), a 0.2% adenine diet (AD, a CKD model), a high-fat diet (HFD, a metabolic model), and a combination of HFD+AD (a potential CKM model). Mice underwent a hind limb ischemia surgery. An array of structural (capillary density, soleus muscle evaluation), and functional assays were performed.ResultsCompared to ND mice, AD mice showed loss of weight (40%) and GFR (90%) (P<0.001). The HFD+AD mice had 23-50% higher weight and GFR than the AD group (P = 0.003). The kidneys of HFD+AD showed tubular atrophy, tubulointerstitial fibrosis, immune infiltration, glomerulomegaly, consistent with glomerular hyperperfusion, hypercholesterolemia, impaired glucose tolerance, and adipophilin in the liver, an early marker of hepatic steatosis, and myocardial fibrosis. Compared to ND mice, the AD and HFD+AD mice showed similar reductions in the hind limb perfusion ratios, microcapillary density, Type II muscle fibers, and increased muscle fibrosis, immune infiltration, and lowest cross-sectional muscle area. Compared to AD, HFD+AD mice showed a lower flux ratio and grip strength, all at a GFR double that of the AD group.ConclusionA combination of HFD+AD in mice displays features of CKD (loss of GFR, renal fibrosis), dysfunctional obesity (dyslipidemia, impaired glucose tolerance, hepatic steatosis and glomerulomegaly), and cardiovascular disease (myocardial fibrosis and PAD) at a higher GFR, consistent with the features of CKM. This model can be explored to probe the mechanisms of CKM syndrome.
Biological Database Mining for LLM-Driven Alzheimer’s Disease Drug Repurposing
Authors: Schmitt Rico Andre , Buelau Konstantin , Martin Leon , Huettl Christoph , Schirner Michael , Stefanovski Leon , Ritter Petra 
Published: December 2024

AbstractINTRODUCTIONThe synergy of structured knowledge and large language models (LLMs) may contribute to identifying drugs for Alzheimer’s disease (AD) drug repurposing (DR). This paper developed a software pipeline that uses LLMs to translate knowledge stored in natural language (such as in scientific texts) to an applicable DR information structure.METHODSAD-related entries in Gene Ontology and DrugBank were integrated into a Knowledge Graph database to inform LLM prompts. Based on the biological process impact, the LLM provided a suitability rating for DR, taking into account the inhibitory effect of drugs on AD driving processes..RESULTSDrugs with a high potential for DR were identified and manually reviewed, also considering adverse effects. Ripretinib and Pertuzumab (both kinase inhibitors) had the highest DR applicable rating across all iterations.DISCUSSIONWe propose retrospective analyses, considering the high-rated drugs and their effect on AD patients as a starting point for further (prospective) research.
CASSIA allows for robust, automated cell annotation in single-cell RNA-sequencing data
Authors: Xie Elliot , Cheng Lingxin , Shireman Jack , Cai Yujia , Liu Jihua , Mohanty Chitrasen , Dey Mahua , Kendziorski Christina 
Published: December 2024

AbstractNumerous methods are available to assign cell type to subpopulations of cells profiled using single-cell RNA-sequencing. Most require a combination of computational and domain-specific expertise, and they frequently yield inconsistent results that can be challenging to interpret. Large language models have the potential to expand accessibility while reducing manual input and improving accuracy, but existing approaches suffer from hyperconfidence, hallucinations, and lack of interpretation. To address these limitations, we developed CASSIA for automated, accurate, and interpretable cell annotation of single-cell RNA-sequencing data.
Yeast Knowledge Graphs Database for ExploringSaccharomyces cerevisiaeandSchizosaccharomyces pombe
Authors: Kumar Mani R , Arulprakasam Karthick Raja , Kutevska An-Nikol , Mutwil Marek , Thibault Guillaume 
Published: December 2024

ABSTRACTBiomedical literature contains an extensive wealth of information on gene and protein function across various biological processes and diseases. However, navigating this vast and often restricted-access data can be challenging, making it difficult to extract specific insights efficiently. In this study, we introduce a high-throughput pipeline that leverages OpenAI’s Generative Pre-Trained Transformer Model (GPT) to automate the extraction and analysis of gene function information. We applied this approach to 84,427 publications onSaccharomyces cerevisiaeand 6,452 publications onSchizosaccharomyces pombe, identifying 3,432,749 relationships for budding yeast and 421,198 relationships forS. pombe. This resulted in a comprehensive, searchable online Knowledge Graph database, available atyeast.connectome.toolsandspombe.connectome.tools, which offers users extensive access to various interactions and pathways. Our analysis underscores the power of integrating artificial intelligence with bioinformatics, as demonstrated through key insights into important nodes like Hsp104 and Atg8 proteins. This work not only facilitates efficient data extraction in yeast research but also presents a scalable model for similar studies in other biological systems.HIGHLIGHTSGenerated Yeast Knowledge Graphs from full-text research articles.Analyzed over 90,000 publications forSaccharomycesandSchizosaccharomycesspecies.Extracted millions of relationships using GPT-based natural language processing.Yeast Knowledge Graphs accessible through interactive web platforms and APIs.Advanced tool enabling insights into gene networks and functional interactions.Abstract Figure
Uncovering the signaling networks of disseminated glioblastoma cellsin vivowith INSIGHT
Authors: Ahn Ryuhjin , D’Souza Alicia D. , Long Lawrence , Cui Yufei , Burgenske Danielle , Bakken Katrina K. , Ott Lauren L. , Carlson Brett L. , Zhou Grace , Yaron-Barir Tomer M. , Kohale Ishwar N. , Whittaker Charles A. , Flower Cameron T. , Wyckoff Jeffrey , Tuma Ann , Johnson Jared L. , Sarkaria Jann , White Forest M. 
Published: December 2024

AbstractDysregulation of intracellular signaling networks underpins cancer. However, a systems-level elucidation of how signaling networks within distinct cell subpopulations drive cancer progressionin vivohas been unattainable due to technical limitations. We developed INSIGHT (INvestigating SIGnaling network of specific cell subpopulation in Heterogeneous Tissue), a new platform technology combining fluorescence-activated cell sorting with ultra-sensitive mass spectrometry to enable phosphoproteomic characterization of rare and discrete cell subpopulations from fixed tissues. We demonstrated the broad utility of INSIGHT by analyzing the oligodendroglial cell-specific signaling network in the mouse brain. We then applied INSIGHT to investigate the rare, disseminated tumor cell subpopulation in glioblastoma patient-derived xenograft models. INSIGHT uncovered a global rewiring of signaling networks with tumor cell dissemination, marked by a transition from proliferation-associated signaling in the primary tumor cells to signaling associated with postsynapse, neuronal migration, and ion homeostasis in disseminated tumor cells. We reveal interconnections between signaling circuitries within the networks, with numerous proteins, including GluA2, exhibiting altered phosphorylation without protein expression changes, emphasizing the role of post-translational modifications in glioblastoma dissemination. We validated key phosphorylation changes and inferred differentially active kinases with tumor spread to offer new systems-level insights into glioblastoma dissemination mechanismsin vivo. INSIGHT is generally applicable to a wide range of biological systems without genetic engineering and provides quantitative phosphorylation and protein expression data for selected cell subpopulations from heterogeneous tissues.
Unveiling the diversity, transmission, and zoonotic potential of microbes in true insectivores
Authors: Li Hongfeng , Huang Zheng Y.X. , Lan Jie , Hu Li , Wei Xuemin , Wang Yuhao , Li Xiujun , Li Yang , Becker Daniel J. , Wei Fuwen , Xu Yifei 
Published: December 2024

AbstractThe Eulipotyphla (true insectivores) is the third largest mammalian order, comprising over 500 species, and could be an important source of human infectious diseases. However, relatively little is known about the diversity of microbes in insectivores and the contribution of insectivores to virus transmission more specifically among wild hosts. In this study, we compiled a comprehensive dataset containing over 400,000 records of insectivores and their associated microbes from 1903 to 2023. Our analyses showed that insectivores host a wide spectrum of 941 microbes, 60% of which are viruses and are predominantly found in the shrew and hedgehog families. Notably, human-associated viruses harbored by shrews and hedgehogs were phylogenetically closely related to those found in humans, suggesting potential bidirectional transmission between insectivores and humans. Moreover, virus-sharing networks revealed that insectivores held the second-most central position for virus sharing, just second to bats, among all mammalian orders. Insectivores had a high proportion of cross-order transmitted viruses, including many human-associated viruses. Dietary diversity, habitat diversity, and distributional traits (e.g. geographical range size, mean latitude, and urban adaptation status) emerged as the key ecological factors contributing to this cross-species virus transmission. Our findings highlight the microbial diversity present in insectivores, indicating this order may act as potential incubators for novel viruses capable of infecting mammals and spreading viruses of public health concern.
OMAnnotator: a novel approach to building an annotated consensus genome sequence
Authors: Bates Sadé , Dessimoz Christophe , Nevers Yannis 
Published: December 2024

AbstractMotivationAdvances in sequencing technologies have enabled researchers to sequence whole genomes rapidly and cheaply. However, despite improvements in genome assembly, genome annotation (i.e. the identification of protein-coding genes) remains challenging, particularly for eukaryotic genomes: it requires combining several approaches (typicallyab initio, transcriptomics, and homology search), each with its own pros and cons. Deciding which gene models to retain in a consensus is far from trivial, and automated approaches tend to lag behind laborious manual curation efforts in accuracy.ResultsHere, we present OMAnnotator, a novel approach to building a consensus annotation. OMAnnotator repurposes the OMA algorithm, originally designed to elucidate evolutionary relationships among genes across species, to integrate predictions from different annotation sources, using evolutionary information as a tie-breaker. We validated OMAnnotator by reannotating theDrosophila melanogasterreference genome and comparing it with the expert-curated reference and results from the automated pipelines BRAKER2 and EvidenceModeller. OMAnnotator produced a consensus annotation that outperformed each individual input and surpassed the existing pipelines. Finally, when applied to three recently published genomes, OMAnnotator gave substantial improvements in two cases, and mixed results in the third, which had already benefited from extensive expert curation.ConclusionWe introduce an original, flexible, and effective approach to annotating genomes by integrating multiple lines of evidence. The method’s robustness is underlined by its successful implementation in re-annotating recently published genomes, opening up new avenues in eukaryotic genome annotation.
Meiotic Sex Chromosome Inactivation: conservation across theDrosophilagenus
Authors: Avelino Camila C. , Mendonca Carolina A. , Goldstein Gabriel , Bernardo Carvalho A. , Vibranovski Maria D. 
Published: December 2024

ABSTRACTThe inherent difference between sex chromosomes in males and females drives conflicts in gene expression, leading to adaptations such as Meiotic Sex Chromosome Inactivation (MSCI). In this study, we explore the evolutionary dynamics of MSCI within theDrosophilagenus by analyzing transcriptomes across different stages of spermatogenesis inD. melanogasterand its progressively more distant relatives,D. simulans,D. willistoni, andD. mojavensis. Stage-specific bulk RNA sequencing, showing a strong correlation in spermatogenic gene expression patterns among these species, revealed that MSCI dates back to the early evolution of theDrosophilagenus, impacting the regulation of both coding and long non-coding RNAs. Notably, for newly evolved genes, X-linked genes show higher expression levels than autosomal genes during mitosis and meiosis, indicating that MSCI predominantly regulates older genes. In contrast, newly evolved autosomal genes exhibit a gradual increase in expression throughout spermatogenesis, reaching their peak in the post-meiotic phase. During this phase, the expression of X-linked new genes decreases, eventually aligning with that of autosomal genes. This expression pattern suggests that haploid selection plays a crucial role in the regulation of new genes, with monoallelic expression of the X chromosome providing an advantage across all stages of germline development, while autosomal gene expression gains a selective edge primarily in the post-meiotic phase. Together, these findings provide new insights into the evolution of sex chromosomes and highlight the critical role of MSCI in shaping gene expression profiles inDrosophila.
Nanobactericides Derived from Cinnamon Bark Extract: Phytochemical Profiling and Antibacterial Efficacy Against Bacterial Panicle Blight in Rice
Authors: Naji Qamar Mohammed , Zulperi Dzarifah Mohamed , Ahmad Khairulmazmi , Hata Erneeza Mohd 
Published: December 2024

ABSTRACTBacterial panicle blight (BPB), caused by the Gram-negative aerobic bacteriumBurkholderia glumae (B.glumae), poses a significant threat to global rice production. Cinnamon bark extract (CBE) has demonstrated potent antioxidant and antimicrobial properties due to its high concentration of bioactive compounds, including eugenol and cinnamaldehyde. To enhance the efficacy and stability of these volatile compounds, this study employed nanotechnology and encapsulation techniques. The objective was to develop a CBE-based nanoformulation to inhibitB. glumaeand control BPB in rice. CBE-chitosan (CBE-CS) nanoformulations were synthesized using ionic cross-linking between chitosan and trisodium phosphate (TPP) at various concentrations (0%, 0.5%, 1%, 2%, and 4% TPP). More than 15 active compounds were identified in CBE, including (Z)-3-Phenylacrylaldehyde, 2-Propenoic acid, 3-(2-hydroxyphenyl), cinnamaldehyde dimethyl acetal, and hexadecanoic acid. Bacterial membrane damage was significantly greater in treatments with CBE compared to untreated controls. The synthesized nanoparticles ranged in size from 43.66 nm to 106.1 nm, with encapsulation efficiencies between 48.65% and 48.78%, and loading capacities between 25.65% and 33.9%. Scanning electron microscopy (SEM) revealed spherical and homogeneous nanoparticles, while FTIR and XRD analysis confirmed the successful encapsulation of CBE in the chitosan nanoparticles. The antibacterial activity of the nanoformulations showed inhibition zones ranging from 7.5 to 11.8 mm, with the CBE-CS formulation containing 0.5% TPP demonstrating the highest efficacy (MIC = 15.6 μmol/ml; MBC = 31.25 μmol/ml).
FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment
Authors: Li Mengdie , Yang Yating , Chen Tangcong , Luo Yueyang , Zhang Yingqian , Liu Huanzhong , Maes Michael 
Published: December 2024

AbstractBackgroundThe demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging is a risk factor for synaptic plasticity damage in the brain and leads to neurocognitive dysfunctions. However, whether FTO is associated with susceptibility to depression in different age groups remains unknown.MethodsWe subjected 3-and 12-month-old C57BL/6J male mice to 6 weeks of chronic unpredictable mild stress (CUMS) and 3 weeks of hippocampal injection of FTO knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 male mice in each 3-month-old and 12-month-old groups were divided into three groups (n=12): Sham, CUMS, and FTO-KD. After 6 weeks, we assessed behavioral deficits (depressive and anxiety-like behaviors and cognitive impairment) by behavioral tests and hippocampal neuronal damage (dendritic spine density, neuronal atrophy, and expression of proteins associated with synaptic plasticity) by molecular biochemical experiments.ResultsThe results showed that 12-month-old C57BL/6J mice were more likely to develop depression-like behavior and spatial learning and memory impairment induced by CUMS than 3-month-old mice. Chronic stress-induced depression-like behavior and cognitive impairment worsened after the FTO-KD intervention. In the hippocampus of 3-and 12-month-old mice, CUMS induced the downregulation of FTO, nerve growth factor (NGF), reelin, and synaptic plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density of dendritic spines, and an increased number of neuronal pyknotic nuclei, leading to neuronal disarray, which was more significant in 12-month-old animals. FTO deficiency accelerated neuronal damage in the hippocampus of 12-month-old CUMS mice.ConclusionsThis study provides rodent evidence that FTO deficiency may increase the susceptibility to depression in older adults by impairing hippocampal neuronal function and neuronal synaptic plasticity in an age-dependent manner. This suggests that the development of FTO activators may be an effective treatment for depression in older adults.