bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interprofessional Collaboration as a Best Practice Across the Care Continuum
Authors: Campagna Vivian , Lee-Riley Lorna 
Published: January 2025

Purpose:
Interprofessional teams are increasingly being recognized as a best practice for enhancing cooperation among multiple disciplines in delivering person-centered care and improving outcomes. Unlike previous models, such as the multidisciplinary team in which each profession or discipline remained largely siloed, with interprofessional teams collaboration occurs across disciplines. For case managers, the interprofessional team concept aligns with the collaborative, professionally diverse nature of the field of practice. As the Commission for Case Manager Certification (CCMC) states: “The practice of case management is professional and collaborative, occurring in a variety of settings where medical care, mental health care, and social supports are delivered. Services are facilitated by diverse disciplines in conjunction with the care recipient and their support system” (2024b, CCMC Definition and Philosophy, p.1). Although interprofessional teams may be more familiar in settings such as acute care, this dynamic can be found, formally and informally, across health and human services. Professional case managers who actively participate in interprofessional teams will likely find more opportunities to optimize collaboration and collective decision-making that bring out the best of every profession and discipline.

Primary Practice Settings:
Interprofessional teams can be found in multiple care settings including acute care, subacute care, community-based care, palliative/end-of-life and other settings that benefit from a person-centered approach that supports successful transitions of care and improved outcomes.

Implications for Case Management Practice:
Professional case managers are valued members of interprofessional teams, in that they are typically collaborative, promote open communication, and encourage cooperation among various disciplines. Interprofessional teams, however, may require a shift in thinking away from the former multidisciplinary model, in which case managers often acted as the hub connecting the spokes of each discipline. Within interprofessional teams, the individual is at the center, and every discipline will share leadership based on the individual’s needs or the treatment protocol or other intervention needed in the moment. In this way, interprofessional teams become a model for empowering and allowing each discipline to step up and address specific aspects of treatment or other interventions.
Barriers to Developmental Care in the NICU
Authors: Logsdon Shelby , Arter Sara 
Published: January 2025

Background:
Variability in developmental care implementation in the neonatal intensive care unit (NICU) highlights the need to explore barriers to care delivery, yet few studies addressed these challenges.

Purpose:
Drawing from NICU literature, this integrative review identifies barriers to implementing developmental care with premature infants.

Methods:
A systematic search of CINAHL and PubMed (2014-2024) was conducted, yielding 2 qualitative and 5 quantitative studies.

Results:
Thematic analysis revealed 3 key barriers based on the theory of planned behavior: attitude, subjective norm, and perceived control.

Conclusions:
To improve developmental care, a multi-pronged approach engaging stakeholders is recommended. Future research should apply rigorous implementation science methods to overcome these barriers.
The Apoprotein E4 isotype does not affect the severity of COVID-19 infection and other flu-like syndromes
Authors: Carvalho-Rassbach Marina , Ventura Lucas Haniel Araujo , Assis Larissa Oliveira , Fabrini Sabrina , Natividade Manuelle Maria Pereira , Silva Janayne Luihan , Gomes Karina Braga , Faria Ana Maria Caetano , Alvarez-Leite Jacqueline I. 
Published: January 2025

Impact of e4 allele on flu-like syndromes
The ɛ4 allele has no influence on flu-like syndrome, including COVID-19. COVID-19 severity was associated with BMI, male sex, comorbidities and IL-4 levels.
Oncogenic Stress is a Novel Immunogenic Signal Driven by the Unfolded Protein Response and Detected by Neutrophils
Authors: Debiesse Antoine , Moudombi Lyvia , Voissière Aurélien , Lefèvre Leïla , Malfroy Marine , Moskalevska Iryna , Pereira Abrantes Manuela , Vanacker Hélène , Hubert Margaux , Pommier Roxane , Assaf Cassandra , Jacquet Emmanuelle , Laurent Marie , Belluco Sara , Goutagny Nadège , Petrilli Virginie , Cherfils-Vicini Julien , Caux Christophe , Bendriss-Vermare Nathalie , Michallet Marie-Cécile 
Published: January 2025

ABSTRACTCellular transformation is initiated by a driver mutation, resulting in the abnormal expression of an oncogene or the loss of a tumor suppressor gene in a normal cell. This event leads to oncogenic stress (OS), describing a disruption of cellular homeostasis which activates stress response pathways and transcriptomic programs that can either promote tumor development or trigger intrinsic safeguards such as senescence or apoptosis. While the immunogenicity of senescent cells is well established, the immunogenic potential of cells at the early OS stage and the mechanisms by which they are sensed by the immune system remain unknown. We developed an originalin vitroOS model using primary human mammary epithelial cells to investigate this process. Our results show that OS cells display an immunoactive secretome associated with OS (SOS), as well as immunogenic membrane ligands. Intrinsically, OS cells activate the PERK and IRE1 branches of the unfolded protein response (UPR) that regulate their immunogenic features. Extrinsically, we demonstrated that neutrophils can detect OS-induced immunogenic signals, leading to their recruitment and their activation in co-culturein vitro. We validated this observation in two spontaneous murine models of breast cancer, where the earliest preneoplastic stages exhibit both UPR activation in epithelial cells and neutrophil infiltration. Altogether, our work identifies OS as the first immunogenic event in carcinogenesis and neutrophils as the first immune cell involved in immunosurveillance, paving the way for potential therapeutic approaches intercepting early steps of tumorigenesis.
Global transcriptome analysis identifies nicotinamide metabolism to play key roles in IFN-γ and nitric oxide modulated responses
Authors: Chattopadhyay Avik , Shyam Sai , Das Shreyasee , Nandi Dipankar 
Published: January 2025

AbstractInterferon-gamma (IFN-γ) is a key regulator of immune responses. A hallmark of the IFN-γ response is inducible nitric oxide (NO) production, driven primarily by nitric oxide synthase 2 (NOS2). In this study, we investigated the influence of NO on the IFN-γ-induced transcriptomic and metabolic changes in the RAW 264.7 macrophage cell line. IFN-γ activation led to NO-dependent lactate production and lower cell survival. Bulk RNA sequencing analysis identified genes differentially expressed early by IFN-γ that were either NO-independent or NO-dependent. Inhibition of NO modulated a minor subset of the transcriptome, notably affectingKlf6(a tumor suppressor) andZfp36(a regulator of pro-inflammatory cytokines). Interestingly, bothKlf6andZfp36correlatively showed high expression in most cancers. The PPI network exhibited dense clustering with scale-free and small-world properties, identifyingStat1,Irf7,Irf1,Cxcl10, andIsg15as top five hubs. The top IFN-γ signalling genes exhibited deficient expression in the brain but were highly expressed in lung, spleen, and EBV-transformed lymphocytes. Gene-disease associations linked the IFN-γ-regulated genes to immunodeficiencies, chronic inflammatory responses and malignancies. Interestingly, IFN-γ upregulated genes were involved in nicotinamide metabolism, suggesting a transcriptional basis for modulation of metabolic pathways. This novel aspect was experimentally tested to show that IFN-γ induced NAD amounts. Importantly, the inhibition of purine nucleoside phosphorylase (using Forodesine hydrochloride) which is involved in the endogenous pathway for NAD generation, lowered IFN-γ induced nitrite and increased cell survivalin vitro. Functionally, enriched nicotinamide metabolism by IFN-γ may regulate inflammatory responses and the implications of our findings are discussed.
In vivodeletion of a GWAS-identifiedMybdistal enhancer acts onMybexpression, globin switching, and clinical erythroid parameters in β-thalassemia
Authors: Deleuze Virginie , Stephen Tharshana , Salma Mohammad , Orfeo Cédric , Jorna Ruud , Maas Alex , Barroca Vilma , Arcangeli Marie-Laure , Andrieu-Soler Charlotte , Grosveld Frank , Soler Eric 
Published: January 2025

AbstractGenome-wide association studies (GWAS) have identified numerous genetic variants linked to human diseases, mostly located in non-coding regions of the genome, particularly in putative enhancers. However, functional assessment of the non-coding GWAS variants has progressed at slow pace, since the functions of the vast majority of genomic enhancers have not been defined, impeding interpretation of disease-susceptibility variants. TheHBS1L-MYBintergenic region harbors multiple SNPs associated with clinical erythroid parameters, including fetal hemoglobin levels, a feature impacting disease severity of beta-hemoglobinopathies such as sickle cell anemia and beta-thalassemia. HBS1L-MYB variants cluster in the vicinity of severalMYBenhancers, altering MYB expression and globin switching. We and others have highlighted the conserved humanMYB-84kb enhancer, known as the -81kb enhancer in the mouse, as likely candidate linked to these traits. We report here the generation of aMyb-81kb enhancer knock-out mouse model, and shed light for the first time on its impact on steady state erythropoiesis and in beta-thalassemiain vivo.
Understanding RNA Chaperone Activity of ProQ Protein
Authors: Singh Shilpi , Kumari Nisha , Dutta Tanmay , Karmakar Tarak 
Published: January 2025

AbstractRNA-binding proteins (RBPs) are crucial in recognizing and binding small RNAs that modulate gene expression. RBPs often act as RNA chaperones facilitating the sRNA-mRNA duplex formation. One of the most studied sRNA chaperones is Hfq, the post-transcriptional gene regulator in bacteria. Recently a new RNA-chaperone protein, ProQ has been discovered, which binds to a novel sRNARaiZ, derived from the 3’-end of mRNA encoding ribosome-inactivating protein, and promotes its base pairing with the ribosome binding site of hupA mRNA leading to the repression of HU-α protein synthesis. Despite these studies, the RNA binding mechanism in ProQ has not been well explored in detail to date. In this work, we studied the binding ofraiZRNA to ProQ using atomistic long-timescale molecular dynamics and on-the-fly probability-based enhanced sampling (OPES) simulations. TheraiZRNA binds to ProQ’s concave surface mostly decorated with polar and positively charged residues like arginine and lysine exerting electrostatic stabilization to the RNA.In-silicomutations of these crucial residues lead to significant loss of the intermolecular interactions resulting in the detachment of the RNA from the protein. The free energy surface obtained from the OPES simulation helps identify stableraiZbound ProQ structures as well as intermediate states. The pertinent atomistic insights into the protein-RNA interactions and deciphering the binding mechanism of theraiZRNA to ProQ enrich our knowledge about ProQ and its RNA chaperone activity.
Weighted gene co-expression network analysis reveals key genes and lncRNAs in desi cattle chronically infected with Johne’s disease
Authors: Sahu Abhisek , Abdullah Mohd , Gupta Saurabh , Singh Shoor Vir , Dhillon Ankush , Yadav Prabhati , Azam Sarwar 
Published: January 2025

AbstractJohne’s disease (JD), caused byMycobacterium aviumsubsp.paratuberculosis(MAP), is a chronic enteric disease with significant economic impacts on the dairy industry. To elucidate molecular mechanisms underlying MAP infection indesicattle (Bos indicus), we conducted a comprehensive transcriptomic study. This revealed 1,905 protein-coding and 3,123 lncRNA genes as differentially expressed in MAP-infected samples, alongside the first comprehensive annotation of 45,947 lncRNAs indesicattle. Weighted Gene Co-expression Network Analysis identified 11 co-expressed gene modules, with the turquoise module comprising 870 protein- coding genes and 934 lncRNAs, highly correlated with clinical traits. Functional enrichment analysis of this key module revealed significant involvement in defense response, inflammatory processes, and NK cell-mediated immunity and cytotoxicity. GSE analysis revealed suppressed pathways, including NK cell immunity and lectin response, facilitating bacterial persistence in chronic infection, while activated pathways included G-protein-coupled receptor signaling and metabolic pathways. Network approach identified 12 hub genes (IL7R, TLR4, KLRK1, IFNG, TGFB1, CD68, CXCR6, GZMB, KLRG1, MMP9, GZMA, SELL) associated with immune suppression, inflammation, and tissue remodeling. Additionally, 22 lncRNAs co-expressed with hub genes suggesting roles in modulating immune regulation. By identifying critical genes and lncRNAs, our study offers potential targets for developing innovative diagnostic and therapeutic strategies for JD.
The Genome ofChenopodium ficifolium: Developing Genetic Resources and a Diploid Model System for Allotetraploid Quinoa
Authors: Ludwig Clayton D. , Maughan Peter J. , Jellen Eric N. , Davis Thomas M. 
Published: January 2025

AbstractHigh-quality nuclear, chloroplast, and preliminary mitochondrial genomes have been assembled and annotated for the B-genome diploid (BB: 2n = 2x = 18) figleaf goosefoot (Chenopodium ficifolium). The primary objective was to advance a simplified model system for genetic characterization and improvement of allotetraploid (AABB: 2n = 4x = 36) quinoa (Chenopodium quinoa), a nutritionally valuable, halophytic orphan crop. In addition to its diploidy and favorably small genome size, theC. ficifoliummodel provides a shorter generational period and smaller overall plant size as compared toC. quinoa, while displaying relevant agronomic trait variations amenable to gene-trait association studies. TheC. ficifolium‘Portsmouth’ nuclear genome was sequenced using PacBio HiFi Long Read technology and assembled using Hifiasm. After manual adjustments, the final ChenoFicP_1.0 assembly consisted of nine pseudochromosomes spanning 711.5 Mbp, while 22,617 genes were identified and annotated. BUSCO analyses indicated a nuclear genome completeness of 97.5%, and a proteome and transcriptome completeness of 98.4 percent. The chloroplast genome assembly detected two equally represented structural haplotypes differing in the orientation of the Short Single Copy region relative to the Long Single Copy region. Phylogenetic and parentage analyses pointed to an unspecified AA diploid species and away fromC. ficifoliumas the likely maternal chloroplast and mitochondrial genome donor(s) during the initial tetraploidization event in theC. quinoalineage. Using the new ChenoFicP_1.0 reference genome, a GWAS was performed on a previously studiedC. ficifoliumF2 population to further define region(s) implicated in the control of three key agronomic traits: days to flowering, plant height, and branch number. This analysis localized control of all three traits to a 7 Mb interval on pseudochromosome Cf4. This region contains approximately 770 genes, including theFTL1locus, thus confirming and extending our prior, single-marker analysis showing association of these three traits with anFTL1amplicon length polymorphism. The use of these data to further developC. ficifoliumas a model species for genetics and breeding of quinoa serves to expand knowledge and germplasm resources for quinoa improvement.
Delivery of a chemically modified noncoding RNA domain improves dystrophic myotube function
Authors: Niasse-Sy Zeinabou , Zhao Bo , Lenardič Ajda , Luong Huyen Thuc Tran , Bar-Nur Ori , Auwerx Johan , Wohlwend Martin 
Published: January 2025

ABSTRACTFast twitch, type II muscle fibers are particularly prone to degradation in skeletal muscle pathologies, such as sarcopenia and muscular dystrophies. We previously showed that endogenous activation of the exercise-induced long noncoding RNA CYTOR promotes fast-twitch myogenesis. In the present study, we identify an independent pro-myogenic element within human CYTOR and optimize its RNA delivery. In human primary myoblasts exogenous, vector-based CYTORexon2recapitulates the effect of full-length CYTOR by enhancing fast-twitch myogenic differentiation. Furthermore, chemically modified CYTORexon2RNAΨU(N1-me-PseudoU, 7-methyl guanosine 5’Cap, polyA tail) enhanced RNA stability and reduced the immunogenic response to CYTORexon2RNA. We demonstrate that viral- or chemically optimized RNA-mediated CYTORexon2administration enhances the commitment towards myogenic maturation in Duchenne muscular dystrophy-derived primary myoblasts, induced myogenic progenitor cells and mouse embryonic stem cells. Furthermore, chemically optimized CYTORexon2improves key disease characteristics in dystrophic myotubes, including calcium handling and mitochondrial bioenergetics. In summary, our findings identify CYTOR exon 2 as the pro-myogenic domain of CYTOR that can be delivered in a disease context using chemical modifications. This is of particular importance given the susceptibility of type II muscle fibers in different muscle pathologies such as aging and dystrophies, and the reported oncogenic effect of CYTOR exon 1. Our study, therefore, highlights the potential of identifying functional domains in noncoding RNAs. Delivery, or targeting of such RNA domains could constitute next-generation RNA therapeutics.
Systems biology framework for rational design of operational conditions forin vitro / in vivotranslation of microphysiological systems
Authors: Cadavid Jose L. , Meimetis Nikolaos , Griffith Linda G. , Lauffenburger Douglas A. 
Published: January 2025

AbstractPreclinical models are used extensively to study diseases and potential therapeutic treatments. Complexin vitroplatforms incorporating human cellular components, known as microphysiological systems (MPS), can model cellular and microenvironmental features of diseased tissues. However, determining experimental conditions -- particularly biomolecular cues such as growth factors, cytokines, and matrix proteins -- providing most effective translatability of MPS-generated information toin vivohuman subject contexts is a major challenge. Here, using metabolic dysfunction-associated fatty liver disease (MAFLD) studied using the CNBio PhysioMimix as a case study, we developed a machine learning framework called LatentIn VitrotoIn VivoTranslation (LIV2TRANS) to ascertain how MPS data map toin vivodata, first sharpening translation insights and consequently elucidating experimental conditions that can further enhance translation capability. Our findings in this case study highlight TGFβ as a crucial cue for MPS translatability and indicate that adding JAK-STAT pathway perturbations via interferon stimuli could increase the predictive performance of this MPS in MAFLD studies. Finally, we developed an optimization approach that identified androgen and EGFR signaling as key for maximizing the capacity of this MPS to capturein vivohuman biological information germane to MAFLD. More broadly, this work establishes a mathematically principled approach for identifying experimental conditions most beneficially capturingin vivohuman-relevant molecular pathways and processes, generalizable to preclinical studies for a wide range of diseases and potential treatments.
ORF1ab Codon Frequency Model Predicts Host-Pathogen Relationship in Orthocoronavirinae
Authors: Davis Phillip E. , Russell Joseph A. 
Published: January 2025

AbstractPredicting phenotypic properties of a virus directly from its sequence data is an attractive goal for viral epidemiology. Here, we focus narrowly on the Orthocoronavirinae clade and demonstrate models that are powerfully predictive for a human-pathogen phenotype with >86% average precision and >99% average recall on the withheld test set groups, using only Orf1ab codon frequencies. We show alternative examples for other viral coding sequences and feature representations that do not perform well and discuss what distinguishes the models that are performant. These models point to a small subset of features, specifically 5 codons, that are critical to the success of the models. We discuss and contextualize how this observation may fit within a larger model for the role of translation in virus-host agreement.
A Simple and Scalable Chopped-Thallus Transformation Method forMarchantia polymorpha
Authors: Batth Rituraj , Poormassalehgoo Andisheh , Bhardwaj Kritika , Kaniecka Elżbieta , Goto-Yamada Shino 
Published: January 2025

AbstractThe liverwortMarchantia polymorphahas emerged as a valuable model for studying fundamental biological processes and the evolutionary history of land plants. Agrobacterium-mediated transformation is widely used for genetic modification ofM. polymorphausing spores, thalli, and gemmae. While spores offer high transformation efficiency, they result in diverse genetic backgrounds due to sexual reproduction. Conversely, thallus- and gemma-based methods maintain genetic consistency but are impractical for large-scale applications. To address these limitations, we developed a novel chopped-thallus transformation method. This technique involves generating numerous plant fragments by chopping thalli, eliminating the need for complex preprocessing. The method demonstrated superior transformation efficiency compared to traditional approaches and achieved sufficient numbers of transformants using simplified Gamborg’s B5 medium, previously considered suboptimal. This scalable and straightforward method enables the generation of large numbers of genetically consistent transformants, facilitating high-throughput experiments, including mutant screening and other large-scale applications.
SCAN-ACT: Adoptive T Cell Therapy Target Discovery Through Single-Cell Transcriptomics
Authors: Testa Stefano , Pal Aastha , Subramanian Ajay , Varma Sushama , Tang Jack Pengfei , Graham Danielle , Arfan Sara , Pan Minggui , Bui Nam Q. , Ganjoo Kristen N. , Dry Sarah , Huang Paul , van de Rijn Matt , Jiang Wei , Kalbasi Anusha , Moding Everett J. 
Published: January 2025

SummaryThe FDA approval of T cell receptor-engineered T cells (TCR-T) for synovial sarcoma demonstrates the potential for adoptive T cell therapies (ACTs) in solid tumors. However, the paucity of tumor-specific targets without expression in normal tissues remains a major bottleneck, especially in rare cancer subtypes. Here, we present a comprehensive computational pipeline called SCAN-ACT that leverages single cell RNA sequencing and multi-omics data from tumor and normal tissues to nominate and prioritize targets for both chimeric antigen receptor (CAR)- and TCR-T cells. For surface membrane targets, SCAN-ACT proposes target pairs for bispecific Boolean logic-gated CAR T cells. For peptide-MHC targets, SCAN-ACT proposes intracellular peptides bound to a diverse set of human leukocyte antigens. We applied the SCAN-ACT pipeline to soft tissue sarcoma (STS), analyzing 986,749 single cells to identify and prioritize 395 monospecific CAR-T targets, 14,192 bispecific CAR-T targets, and 5,020 peptide-MHC targets for TCR-T cells. Selected targets were validated experimentally by protein expression and for peptide-MHC binding. Proposed targets and target pairs reflected the mesenchymal, neuronal, and hematopoietic ontogeny of STS. This work provides a robust data repository along with a web-based and user-friendly set of analysis tools to accelerate ACT development for solid tumors.