bluuebunny/crossref_metadata_2025_split huggingface dataset:
What If…The Impact of Institutional Accreditation on PA Programs Transitioning to an Entry-Level Professional Doctorate Degree
Authors: Snyder Jennifer A. , Miller Anthony 
Published: December 2024

Introduction
There are several ramifications of a potential degree transition to an entry-level doctoral degree for Physician Assistant (PA) programs. The purpose of this article is to investigate the impact on institutional accreditation and transitioning to an entry level doctoral degree. To understand the potential impact on racial diversity, a subset of programs was further reviewed.

Methods
The Standards from the Accreditation Review Commission for PA Education (ARC-PA) and the six Institutional Accreditation commissions that recognize institutions were reviewed. The accreditation outcomes from all ARC-PA accredited programs' institutions were reviewed.

Results
The majority of PA programs, including those that graduate the highest diverse populations of PAs, are already recognized as comprehensive or doctoral degree granting institutions. This means they would likely not encounter significant accreditation challenges in an application to transition. Most PA programs meet the requirements for credit hour, length of program, and expectations of ‘substantial mastery' of the content in the curriculum to satisfy institutional accreditation requirements at the professional doctoral degree level. The faculty qualifications and level of scholarship required would need to be in compliance with the institutional accreditor's expectations.

Discussion
This paper highlighted the general institutional accreditation requirements that would need to be met in order to establish a PA doctoral program. Fortunately, the standards tend to be broad and if the PA program can meet ARC-PA Standards, it is likely the institutional accreditor standards would be satisfied.
Combiningin vivo2-photon imaging with photoactivatable fluorescent labeling reveals strikingly low rates of mitochondrial dynamics in skeletal muscle
Authors: O’Reilly Colleen L. , Davidyan Arik , Cizio Katarzyna , Doidge Stephen M. , Bubak Matthew P. , Borowik Agnieszka K. , Lewis Tommy L. , Miller Benjamin F. 
Published: December 2024

AbstractMitochondrial dynamics involve two distinct and opposing processes, fusion and fission. Traditionally we assess fusion and fission by snapshots of protein markers at distinct time points orin vitromodels to infer outcomesin vivo. Recent technological advancements enable visualization of mitochondrial dynamicsin vivousing fluorescent microscopy. Our study modified this technique to evaluate mitochondrial dynamics in skeletal muscle, comparing young (6mo) and old (24mo) micein vivoand contrasting this toex vivoandin vitromodels. We hypothesized thatin vitroandex vivomodels would have higher rates of dynamics thanin vivomodels and that young animals would have higher rates than old animals. We electroporated mitochondrial matrix-targeted photo-activatable GFP into the tibialis anterior (TA) of young and old C57Bl6 mice and imaged using multiphoton microscopy. We also measured rates of mitochondrial dynamics using single fibers isolated from the TA of the electroporated mice, as well as C2C12 myotubes transfected with the same plasmids. We found that the rates of dynamic eventsin vivoare slower than previously indicated, with the C2C12 myoblasts having the fastest rates of dynamic events across all models. We also observed that dynamic rates are slower in old animals compared to young animals. Finally, we found that rates of dynamic events were higher in old animals after an acute bout of exercise. Our data demonstrate it is possible to directly measure rates of mitochondrial dynamicsin vivo. This technique provides a powerful tool to answer experimental questions about mitochondrial dynamics of skeletal muscle.
A generative deep learning approach for global species distribution prediction
Authors: Yan Yujing , Shao Bin , Davis Charles C. 
Published: December 2024

AbstractAnthropogenic pressures on biodiversity necessitate efficient and highly scalable methods to predict global species distributions. Current species distribution models (SDMs) face limitations with large-scale datasets, complex interspecies interactions, and data quality. Here, we introduce EcoVAE, a framework of autoencoder-based generative models trained separately on nearly 124 million georeferenced occurrences from taxa including plants, butterflies and mammals, to predict their global distributions at both genus and species levels. EcoVAE achieves high precision and speed, captures underlying distribution patterns through unsupervised learning, and reveals interspecies interactions viain silicoperturbation analyses. Additionally, it evaluates global sampling efforts and interpolates distributions without relying on environmental variables, offering new applications for biodiversity exploration and monitoring.
Coral reef habitat complexity decreases and diversifies local availability of light
Authors: Brambilla Viviana , Madin Joshua S. , Boutros Nader , Fontoura Luisa , Hoogenboom Mia , Pizarro Oscar , Torres-Pulliza Damaris , Williams Stefan , Woods Rachael Maree , Zawada Kyle J. A. , Dornelas Maria 
Published: December 2024

AbstractThe spatial distribution of environmental conditions can determine where organisms can and cannot live. When the distribution of microhabitats within a landscape is mediated by the shape of its surface, structural complexity can indirectly affect environmental niche distributions. This study investigates how light availability patterns change along a gradient of landscape complexity measured as surface rugosity and height range in tropical shallow reefs. We used 260,000 high frequency and high spatial resolution light measurements across 903 locations to determine the proportion of light that is available at the reef surface. We find that light available on the reef surface is highly variable, with close locations within reef sites experiencing up to 25.7 mol/m2d of daily photon input difference. After accounting for light attenuation due depth, light availability decreases with increasing surface rugosity: a unit increase in local surface rugosity corresponds to an 11-29% decrease in light availability. Local surface complexity can affect the distributions of light availability at local scales, while broader extent site metrics do not capture this variability. Our results suggest that structural complexity enhances local environmental variability, and its indirect effects on other environmental variables and their interactions are essential for understanding ecosystem processes.
Prohibitin 2 is a Key Regulator of T Cell Proliferation and Effector Functions
Authors: Vogt Johannes F. , Merkwirth Carsten , Adams-Quack Petra , Zurkowski Elena , Michna Thomas , Nurbekova Assel , Distler Ute , Yurugi Hajime , Reißig Sonja , Wunderlich F. Thomas , Rajalingam Krishnaraj , Tenzer Stefan , Methner Axel , Langer Thomas , Waisman Ari , Hövelmeyer Nadine 
Published: December 2024

AbstractProhibitin 2 (PHB2) is a highly conserved protein with essential roles in cell homeostasis and survival across different cell types. Previous studies have shown that the deletion of PHB2 results in an arrest in proliferation due to impaired mitochondrial function regulated by the dynamin-like GTPase OPA1. The function of PHB2 in immune cells remains unclear, however, some studies suggest that PHB2 plays a role in the cell membranes of B and T cells. In order to elucidate the role of PHB2 in immune cells, we generated PHB2-deficient T cells. Our findings reveal a pivotal role for PHB2 in the proliferation and differentiation of T cells. PHB2 deficiency inhibits T cell proliferation by inducing a cell cycle arrest at the G1 to S phase, thereby preventing the differentiation into effector T cells. Furthermore, in contrast to previous reports, T cells lacking PHB2 are more resistant to apoptosis. Metabolic analysis reveals that PHB2-deficient T cells fail to upregulate their glycolysis and oxidative phosphorylation upon activation, thus rendering them incapable to proliferate.
Construction of a ceRNA network specific for granulosa cells in PCOS
Authors: Derevyanchuk E.G. , Butenko E.V. , Shkurat T.P. , Lipovich L. 
Published: December 2024

AbstractBackgroundPolycystic ovary syndrome (PCOS) is a hormonal disease with a polygenic genetic model that occurs in 8 – 13% of women of reproductive age. In this study we constructed the granulose cell-specific competitive endogenous RNA (ceRNA) network in polycystic ovary syndrome. The ceRNA network analysis may provide novel insights into PCOS pathophysiology and identify potential therapeutic targets.Materials and methodsThe study included 6 women aged 26 to 34 years old: 3 women with PCOS and 3 women of the control group who underwent IVF procedure. Before RNA extraction GCs from three follicle samples of each group were collected and randomly pooled together as one mixed sample. Using RNA-sequencing we defined the microRNAs, lncRNAs and mRNAs expression profiles of GCs. The analysis of differential gene expression was performed using the DESeq v.1.39.0. The analysis of the interaction of microRNAs and lncRNAs was performed using RNAhybrid; of microRNAs and mRNAs - using the miRWalk database. Cytoscape 3.10.0 software was used to construct the ceRNA network.ResultsAs a result of the differential gene expression analysis using the DESeq package we identified 3 differentially expressed microRNAs in PCOS, 132 - lncRNAs and 564 - mRNAs. The final ceRNA network included 3 microRNAs, 105 lncRNAs and 252 mRNAs.ConclusionThis research underscores the importance of understanding ceRNA networks as a pathway for discovering biomarkers and developing treatments tailored to the unique challenges faced by individuals with PCOS. Further research is warranted to validate the identified interactions and explore their potential as diagnostic and therapeutic targets.
Data-Independent Acquisition (DIA)-Based Label-Free Redox Proteomics (DIALRP) Reveals Novel Oxidative Stress Responsive Translation Factors
Authors: Kobayashi Daiki , Takami Tomoyo , Matsumoto Masaki 
Published: December 2024

AbstractOxidative stress is a key factor in numerous physiological and pathological processes, including aging, cancer, and neurodegenerative diseases. Protein cysteine residues are particularly susceptible to oxidative stress-induced modifications that can alter their structure and function, thereby affecting intracellular signaling pathways. In this study, we developed a data-independent acquisition mass spectrometry (DIA-MS)-based label-free redox proteomics method, termed DIALRP, to comprehensively analyse cysteine oxidative modifications in the prostate cancer cell line DU145 under oxidative stress induced by menadione (MND). Through these analyses, we identified translation-related factors with significantly elevated cysteine oxidation upon MND treatment and evaluated their functional relevance. Notably, our data demonstrated that the inhibition of EIF2, EIF6, and EEF2 complex formation due to oxidative stress occurs during the cellular response to translational inhibition. These insights reveal a previously unrecognized mechanism of translation regulation under oxidative stress and provide a valuable framework for future studies on redox-mediated cellular processes.
White Spot Syndrome Virus Immediate-Early Protein (wsv100) Antagonizes the NF-κB Pathway to Inhibit Innate Immune Response in shrimp
Authors: Xiao Bang , Kang Fang , Li Qianqian , Pan Junming , Wang Yue , He Jianguo , Li Chaozheng 
Published: December 2024

AbstractViruses have evolved sophisticated strategies to evade host immune defenses, often targeting conserved signaling pathways. In shrimp, the NF-κB signaling pathway is crucial for antiviral immunity, yet its regulation during White Spot Syndrome Virus (WSSV) infection remains poorly understood. Here, we identify and characterize wsv100, an immediate-early (IE) protein of WSSV, as a key antagonist of the NF-κB pathway. wsv100 interacts directly with the transcription factor Dorsal and the adaptor protein IMD, preventing Dorsal phosphorylation by Pelle kinase. This inhibition suppresses Dorsal’s nuclear translocation and downstream expression of antimicrobial peptides (AMPs), essential for antiviral defense. Knockdown of wsv100 reduced WSSV replication, increased Dorsal phosphorylation, and enhanced AMP expression, leading to higher survival rates in infected shrimp. Conversely, wsv100 overexpression promoted WSSV replication and AMPs suppression. These findings reveal a novel immune evasion mechanism by which WSSV subverts the NF-κB pathway and highlight the evolutionary arms race between hosts and viruses. This study enhances our understanding of host-virus interactions and offers potential targets for antiviral strategies in shrimp aquaculture.Author SummaryThe innate immune system is the first line of defense against viral infections in invertebrates, with the NF-κB signaling pathway playing a central role in orchestrating antiviral responses. In this study, we uncover a novel immune evasion mechanism employed by White Spot Syndrome Virus (WSSV), a devastating pathogen in shrimp aquaculture. The WSSV immediate-early protein wsv100 directly targets the transcription factor Dorsal and prevents its phosphorylation by Pelle kinase, a critical step in NF-κB activation. This interaction suppresses Dorsal’s nuclear translocation and downstream expression of antimicrobial peptides (AMPs), thereby impairing the shrimp’s ability to mount an effective immune response. Knockdown of wsv100 significantly reduced WSSV replication and enhanced shrimp survival, while wsv100 overexpression had the opposite effect. These findings not only elucidate how WSSV exploits the NF-κB pathway but also underscore its central role in shrimp antiviral immunity. This work advances our understanding of host-virus co-evolution and provides a foundation for developing novel antiviral strategies to mitigate the economic losses caused by WSSV in shrimp aquaculture.
Identification of a minimalAludomain required for retrotransposition
Authors: Moldovan John B. , Yin John , Moran John V. 
Published: December 2024

ABSTRACTAluelements are primate-specific retrotransposon sequences that comprise ∼11% of human genomic DNA.Alusequences contain an internal RNA polymerase III promoter and the resultantAluRNA transcripts mobilize by a replicative process termed retrotransposition.Aluretrotransposition requires the Long INterspersed Element-1 (LINE-1) open reading frame 2-encoded protein (ORF2p). Current models propose thatAluRNA binds to signal recognition particle proteins 9 and 14 (SRP9/14) and localizes to ribosomes, which allowsAluto ‘hijack’ L1 ORF2p. Here, we used HeLa cell-based retrotransposition assays to define a minimalAludomain necessary for retrotransposition. We demonstrate thatAlutranscripts expressed from a cytomegalovirus (CMV) RNA polymerase II promoter can efficiently undergo retrotransposition. The use of an external CMV promoter to expressAluRNA allowed us to construct separation-of-function mutations to examine the effects of large deletions within theAlusequence on retrotransposition. Deletion mutagenesis demonstrated that a 46 nucleotide (nt) domain located at the 5′ end of theAluRNA transcript is necessary forAluretrotransposition. Consistent with current models, the 46 nt 5′Aludomain associates with SRP9/14 in HeLa-HA cell extracts and can promote a single round of retrotransposition in HeLa-HA cells. We propose that the 46 nt 5′Aludomain forms a discrete structure that allows for SRP 9/14 binding and ribosomal association, thereby allowing theAlupoly(A) tract to compete with the L1 poly(A) tail for ORF2p RNA binding to mediate its retrotransposition.
IVISc-L: A quick and simplein vivoassay to study the regulation of gene expression
Authors: Som Saubhik , Vishalakshi Gopalapura J , Manjunath Lekha E , Manna Debraj , Vasu Kirtana , Singh Anumeha , Eswarappa Sandeep M 
Published: December 2024

ABSTRACTSeveral methods are available to study the regulation of gene expression at cellular and molecular levels. Adaptation of these methodsin vivois cumbersome and often requires animal sacrifice. Here, we report an assay (IVISc-L,In VivoImaging of Subcutaneous Luminescence) to study gene regulationin vivo. This assay involves subcutaneous injection of a plasmid DNA encoding firefly luciferase, whose expression is under the regulatory mechanism to be investigated. We could infer its regulated expression by detecting the subcutaneous luminescence using anin vivoimaging system. Using this assay, we have demonstrated the regulation of gene expression mediated by a promoter, micro-RNAs, stop codon readthrough, and rare codons. This minimally invasive assay does not require animal sacrifice or any tissue extraction. The entire assay can be completed within 24 hours. Therefore, this assay will be useful in investigating the mechanisms of gene expression regulation, and screening molecules that can alter gene expressionin vivo.
Analysis of Epidemiology and Drug Resistance Patterns of ESKAPE and Non-ESKAPE pathogens at Nigde Hospital in Turkey: A Retrospective Study (2022–2024)
Authors: Salim Mohammed A. , Budak Diler Songül , Köklü Ramazan , Polat Fikriye , Hajhamed Nooh Mohamed , Özturk Ali 
Published: December 2024

AbstractPurposeThis study, aimed at determining the epidemiology and antimicrobial susceptibility patterns of infectious diseases caused by ESKAPE and non-ESKAPE microorganisms in patients hospitalized at the Nigde Ömer Halisdemir University Training and Research Hospital in Nigde, Turkey, is a crucial step in understanding and combating the global public health problem posed by the ESKAPE pathogens.Materials and methodsA retrospective analysis was conducted at a primary tertiary care teaching reference hospital in Nigde. The study included patients admitted to the hospital between June 2022 and June 2024. The hospital information system offered clinical and demographic data for the patients. Furthermore, the hospital’s microbiology lab acquired information on bacterial isolates and antibiotic resistance.ResultsThis study included 13378 bacterial isolates, predominantly gram-negative bacteria, particularly those from the Enterobacterales group. Among these isolates, 9798 (73.2%) were identified as ESKAPE pathogens, and 3580 (26.8%) were identified as non-ESKAPE bacteria. The Intensive Care Unit (ICU) accounted for the highest proportion of infections (34.47%), followed by the pediatric unit (22.6%). The most common infections were caused byEscherichia coli(4747 isolates, 35.5%),K. pneumoniae(1921 isolates, 19.6 %), andAcinetobacter baumannii(1049 isolates, 10.7 %). Furthermore, the analysis revealed that approximately 50.86% of the ESKAPE isolates were classified as multidrug-resistant (MDR) or extensively drug-resistant (XDR). XDR was predominantly detected inAcinetobacter baumannii(72.4%), whereas MDR was predominantly detected inEnterococcus faecium(76.9%). In contrast, Non MDR was predominantly detected across non-ESKAPE pathogens inStaphylococcus hemolyticus(96.1%),Staphylococcus epidermidis(86.5%), andStaphylococcus hominis(84.5%). Demographic data from the study highlighted significant age group disparities in individuals infected by the ESKAPE and the non-ESKAPE bacteria, with a more substantial proportion of older and children individuals represented in the research sample.ConclusionsThis study underscores the significant threat posed by multidrug-resistant ESKAPE pathogens in reference hospital settings, emphasizing the urgent need for effective surveillance and control measures.
A dual readout embryonic zebrafish xenograft model of rhabdomyosarcoma to assess clinically relevant multi-receptor tyrosine kinase inhibitors
Authors: Wragg Joseph W. , Gray Emma L. , Monteiro Rui , Morris Jo R. , Beggs Andrew D. , Müller Ferenc , Gatz Susanne A. 
Published: December 2024

AbstractBackgroundRhabdomyosarcoma (RMS) is a highly aggressive soft tissue sarcoma, affecting children and adolescents, with poor prognosis in some patient groups. Better therapeutic regimens and preclinical models to test them in are needed. Multi-receptor tyrosine kinase inhibitors (MRTKIs) are licensed for adult indications and explored in the clinic in sarcoma patients. The MRTKI Regorafenib is currently assessed in the relapse setting in patients with RMS (NCT04625907). Reliable biomarkers of response for MRTKIs are lacking. MRTKIs act not only against the cancer cell, but also the supporting stroma, particularly the vasculature. The embryonic zebrafish is translucent and allows assessment of this interaction with high-throughputin vivoimaging.MethodsA new preclinical embryo zebrafish xenograft model was developed using Tg(flk1:GFP) (blood vessel reporter) transgenic zebrafish embryos inoculated in the yolk with fluorescently labelled cells from 7 different RMS cell lines (fusion-positive (FP): Rh4, Rh30, Rh41, RMS-01, fusion-negative (FN): RD, JR1, SMS-CTR), and patient-derived cells IC-pPDX-104 at 50 hours post-fertilization and incubated at 34°C for up to 70 hours. Xenografts and vessel beds were imaged and analysed using custom FIJI pipelines. MRTKIs regorafenib and infigratinib were used at a concentration of 0.1uM added to the fish water 4 hours post cell inoculation. Pro-angiogenic growth factors VEFG-A, FGF-2 and PDGF-BB were measured in conditioned media of each cell line.ResultsAll 7 RMS cell lines and the patient-derived cells engrafted with tumour burden assessment by fluorescent imaging and direct cell counting indicating adequate growth and high cell viability during the observation period. RMS tumours induced neo-vascularisation towards the tumour and increased density of proximal vessel beds. MRTKI treatment revealed a greater tumour-intrinsic sensitivity of FP cells, but identified a significant blockade of neo-vascularisation across all RMS lines, with regorafenib response correlated with secretion of VEGF-A.ConclusionWe have developed an embryonic zebrafish xenograft model of RMS, which allows assessment of tumour growth, vascularisation initiation and therapeutic responses to clinically relevant MRTKIs. The identification of VEGF-A secretion as potential biomarker for Regorafenib response and the separation of therapeutic effects on tumour growth and neovascularisation suggests additional value of our model for response prediction to MRTKIs.