bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Risk of Catheter-Related Thrombosis in Breast Cancer Patients With Implanted Ports
Authors: Luo Zebing , Xu Wanzhu , Guo Zhijun , Xu Manjia , Lv Xinxian , Chen Chujun 
Published: February 2025

Objective
This study assessed the risk factors for thrombosis related to totally implantable venous access ports (TIVAPs) among breast cancer patients.

Methods
A single-center, retrospective, observational study was conducted. Demographic, disease-related, hematological, and TIVAP-related factors were assessed. Multiple logistic regression analysis was used to explore the influencing factors of TIVAP-related thrombosis.

Results
A total of 416 patients with breast cancer with TIVAPs were divided into 3 groups: no thrombosis (64.4%), asymptomatic thrombosis (32.3%), and symptomatic thrombosis (3.3%). Multiple logistic regression showed that with no thrombosis as the reference, the protective factors for asymptomatic thrombosis were chemotherapy and TIVAP placement in the left side of the chest wall. Risk factors were ≤1 comorbidity and the use of ceramics as the base material of the TIVAP reservoir. With no thrombosis as the reference, cancer clinical stage III and chemotherapy were identified as protective factors of symptomatic thrombosis.

Conclusion
Among breast cancer patients with a TIVAP, 32.3% had asymptomatic thrombosis and 3.3% had symptomatic thrombosis. Clinical staff should pay close attention to these indicators and identify high-risk patients with TIVAP-related thrombosis as early as possible.
Continuous Glucose Monitoring for Inpatients on Intravenous Insulin
Authors: Good Karen , Joshi Renu , Snell Vanessa 
Published: February 2025

Purpose
This article describes a protocol used to implement a continuous glucose monitoring program for patients treated with intravenous insulin.

Description
Although continuous glucose monitoring is not indicated for use in hospitalized patients, the COVID-19 pandemic created an immediate need to effectively address the increasing number of people hospitalized with hyperglycemia. The article highlights the implementation process and key glycemic outcomes, discusses the impact of continuous glucose monitoring use on staff time and healthcare resource utilization, and provides information about program expansion.

Outcome
Most patients achieved established glycemic targets. Our program improved staff safety by reducing their exposure to infection. Use of continuous glucose monitoring decreased staff time by almost 2 hours per person per day compared with point-of-care testing and resulted in an average cost savings of $278.00 per patient.

Conclusion
Continuous glucose monitoring is safe and effective in managing glycemia among patients treated with intravenous insulin.
Multi-Metal Resistant Staphylococcus warneri strain TWSL_1: Revealing Heavy Metal Resistant Genomic Features by Whole Genome Sequencing
Authors: Dissanayake Dilani , Chandrasekharan2 Naduviladath , Wijayaratahna Dilrukshi 
Published: February 2025

This study explores the genomic basis of heavy metal resistance in Staphylococcus warneri strain TWSL_1, isolated from industrial textile effluent. The strain exhibited strong resistance to Cd²⁺, Pb²⁺, and Cu²⁺, with minimum inhibitory concentrations of 50 mg/L, 1200 mg/L, and 75 mg/L, respectively. Whole-genome sequencing revealed a 2.66 Mb genome with 2,567 coding sequences and a 99.81% average nucleotide identity to S. warneri WS479. Comparative analysis identified key metal resistance genes, including cadmium efflux and cobalt-zinc-cadmium resistance proteins, absent in S. aureus RF122. Phylogenetic analysis confirmed its classification within S. warneri, with strong bootstrap support (100). Functional annotation highlighted metabolic versatility and stress response capabilities, supporting its adaptation to metal-rich environments. S. warneri TWSL_1 demonstrated high Pb²⁺ removal efficiency, reducing concentrations by over 70%, underscoring its bioremediation potential. These findings highlight S. warneri TWSL_1 as a promising candidate for heavy metal bioremediation, warranting further functional validation and application in environmental detoxification strategies.
Identification and classification of ion-channels across the tree of life: Insights into understudied CALHM channels
Authors: Taujale Rahil , Park Sung Jin , Gravel Nathan , Soleymani Saber , Carter Rayna , Boyd Kennady , Keuning Sarah , Ruan Zheng , Lü Wei , Kannan Natarajan 
Published: February 2025

AbstractThe ion channel (IC) genes encoded in the human genome play fundamental roles in cellular functions and disease and are one of the largest classes of druggable proteins. However, limited knowledge of the diverse molecular and cellular functions carried out by ICs presents a major bottleneck in developing selective chemical probes for modulating their functions in disease states. The wealth of sequence data available on ICs from diverse organisms provides a valuable source of untapped information for illuminating the unique modes of channel regulation and functional specialization. However, the extensive diversification of IC sequences and the lack of a unified resource present a challenge in effectively using existing data for IC research. Here, we perform integrative mining of available sequence, structure, and functional data on 419 human ICs across disparate sources, including extensive literature mining by leveraging advances in large language models to annotate and curate the full complement of the “channelome”. We employ a well-established orthology inference approach to identify and extend the IC orthologs across diverse organisms to above 48,000. We show that the depth of conservation and taxonomic representation of IC sequences can further be translated to functional similarities by clustering them into functionally relevant groups, which can be used for downstream functional prediction on understudied members. We demonstrate this by delineating co-conserved patterns characteristic of the understudied family of the Calcium Homeostasis Modulator (CALHM) family of ICs. Through mutational analysis of co-conserved residues altered in human diseases and electrophysiological studies, we show that evolutionary-constrained residues significantly alter gating functions. Thus, by providing new tools and resources for performing large comparative analyses on ICs, this study addresses the unique needs of the IC community and provides the groundwork for accelerating the functional characterization of dark channels for therapeutic intervention.
A pathogenic subpopulation of human glioma associated macrophages linked to glioma progression
Authors: Hei Yu Kenny Kwok , Abou-Mrad Zaki , Törkenczy Kristof , Schulze Isabell , Gantchev Jennifer , Baquer Gerard , Hopland Kelsey , Bander Evan D. , Tosi Umberto , Brennan Cameron , Moss Nelson S. , Hamard Pierre-Jacques , Koche Richard , Lareau Caleb , Agar Nathalie Y.R. , Merghoub Taha , Tabar Viviane 
Published: February 2025

SummaryMalignant gliomas follow two distinct natural histories:de novohigh grade tumors such as glioblastoma, or lower grade tumors with a propensity to transform into high grade disease. Despite differences in tumor genotype, both entities converge on a common histologically aggressive phenotype, and the basis for this progression is unknown. Glioma associated macrophages (GAM) have been implicated in this process, however GAMs are ontologically and transcriptionally diverse, rendering isolation of pathogenic subpopulations challenging. Since macrophage contextual gene programs are orchestrated by transcription factors acting oncis-acting promoters and enhancers in gene regulatory networks (GRN), we hypothesized that functional populations of GAMs can be resolved through GRN inference. Here we show via parallel single cell RNA and ATAC sequencing that a subpopulation of human GAMs can be defined by a GRN centered around the Activator Protein-1 transcription factor FOSL2 preferentially enriched in high grade tumors. Using this GRN we nominate ANXA1 and HMOX1 as surrogate cell surface markers for activation, thus permitting prospective isolation and functional validation in human GAMs. These cells, termed malignancy associated GAMs (mGAMs) are pro-invasive, pro-angiogenic, pro-proliferative, possess intact antigen presentation but skew T-cells towards a CD4+FOXP3+ phenotype under hypoxia. Ontologically, mGAMs share somatic mitochondrial mutations with peripheral blood monocytes, and their presence correlates with high grade disease irrespective of underlying tumor mutation status. Furthermore, spatio-temporally mGAMs occupy distinct metabolic niches; mGAMs directly induce proliferation and mesenchymal transition of low grade glioma cells and accelerate tumor growth in vivo upon co-culture. Finally mGAMs are preferentially enriched in patients with newly transformed regions in human gliomas, supporting the view that mGAMs play a pivotal role in glioma progression and may represent a plausible therapeutic target in human high-grade glioma.
Therapeutic assessment of a novel mitochondrial complex I inhibitor inin vitroandin vivomodels of Alzheimer’s disease
Authors: Trushin Sergey , Nguyen Thi Kim Oanh , Stojacovic Andrea , Ostroot Mark , Deason J. Trey , Chang Su-Youne , Zhang Liang , Macura Slobodan I. , Nambara Toshihiko , Lu Wenyan , Kanekiyo Takahisa , Trushina Eugenia 
Published: February 2025

AbstractDespite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development of disease-modifying strategies targeting the underlying mechanisms of Alzheimer’s disease (AD) is urgently needed. We demonstrate that mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signaling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design and structure‒activity relationship studies yielded novel mtCI inhibitors profiled in a drug discovery funnel designed to address their safety, selectivity, and efficacy. The new lead compound C458 is highly protective against Aβ toxicity, has favorable pharmacokinetics, and has minimal off-target effects. C458 exhibited excellent brain penetrance, activating neuroprotective pathways with a single dose. Preclinical studies in APP/PS1 mice were conducted via functional tests, metabolic assessment,in vivo31P- NMR spectroscopy, blood cytokine panels,ex vivoelectrophysiology, and Western blotting. Chronic oral administration improved long-term potentiation, reduced oxidative stress and inflammation, and enhanced mitochondrial biogenesis, antioxidant signaling, and cellular energetics. These studies provide further evidence that the restoration of mitochondrial function and brain energetics in response to mild energetic stress represents a promising disease- modifying strategy for AD.
Coordinated macrophage and T cell interactions mediate response to checkpoint blockade in colorectal cancer
Authors: Mestrallet Guillaume , Brown Matthew , Vaninov Natalie , Cho Nam Woo , Velazquez Leandra , Ananthanarayanan Aparna , Spitzer Matthew , Vabret Nicolas , Cimen Bozkus Cansu , Samstein Robert M , Bhardwaj Nina 
Published: February 2025

SummaryMismatch repair deficiency (MMRd), either due to inherited or somatic mutation, is prevalent in colorectal cancer (CRC) and other cancers. While anti-PD-1 therapy is utilized in both local and advanced disease, up to 50% of MMRd CRC fail to respond. Using animal and human models of MMRd, we determined that interactions between MHC+ C1Q+ CXCL9+ macrophages and TCF+ BHLHE40+ PRF1+ T cell subsets are associated with control of MMRd tumor growth, during anti-PD-1 treatment. In contrast, resistance is associated with upregulation of TIM3, LAG3, TIGIT, and PD-1 expression on T cells, and infiltration of the tumor with immunosuppressive TREM2+ macrophages and monocytes. By combining anti-PD-1 with anti-LAG3/CTLA4/TREM2, up to 100% tumor eradication was achieved in MMRd CRC and remarkably, in >70% in MMRp CRC. This study identifies key T cell and macrophage subsets mediating the efficacy of immunotherapy in overcoming immune escape in both MMRd and MMRp CRC settings.Abstract FigureHighlightsAnti-PD-1 therapy leads to the accumulation and colocalization of MHCI/II+ C1Q+ CXCL9+ macrophages and DCs with TCF+ CCL5+ T cells that have high TCR diversity.Resistance to anti-PD-1 therapy involves multiple T cell checkpoints, TREM2+ macrophages, IL1B+ TREM1+ monocytes and neutrophils, and IFITM+ tumor cells.Simultaneous blockade of PD-1, LAG3, CTLA-4 and TREM2 dramatically prevents progression of both MMRd and MMRp tumors.Combination therapy completely eliminates tumors by leveraging MHC+ macrophage, CD4+ and CD8+ T cell interactions, facilitating durable anti-tumor effects.
IMMUNOGENICITY AND SAFETY OF CHICKEN EMBRYO FIBROBLAST ADAPTED FOWLPOX VACCINE
Authors: Okafor Uchenna Somtochukwu , Israel Stephen , Meseko Clement Adebajo , Adediran Oyeduntan Adejoju , Ogunmolawa Oluyemi Rotimi , Darang Anthony B. , Bwala Dauda Garba 
Published: February 2025

ABSTRACTBackgroundThe use of chorioallantoic membranes (CAM) route for the propagation of fowlpox virus (FPV) is the method applied in the production of potent and effective fowlpox vaccine at the National Veterinary Research Institute (NVRI), Vom. However, production insufficiency has led to inadequate supply of vaccine to meet farmer’s demands. This has left large number of susceptible and unvaccinated flocks with outbreaks of the disease being reported in Nigerian.AimThis study adapted FPV to Chicken embryo fibroblast (CEF) cell culture and assessed its immunogenicity and safety of the resulting vaccine in comparison to a locally produced CAM-based FPV vaccine.MethodsThe FPV were propagated on CAM and CEF of 9 to 12 day old developing chicken embryos. The vaccine harvests were subjected to quality checks, titrated, and used in vaccinating experimental birds via the wing web to monitor for takes, seroconversion, and safety.ResultsThe FPV was successful adapted to CEF as demonstrated by the attainment of 80 to 90% cytopathic effect within 71 to 115 hours in the different passages. Both the CEF and CAM-adapted vaccine harvests were highly replicative producing titres of above 106.0/ml TCID50,but higher titres of 108.25/ml TCID50was recorded in the CEF-adapted vaccines. Experimentally vaccinated birds showed 100% takes within 3 to 4 days post-vaccination, with no adverse effects recorded.ConclusionThis research reported successful development and adaptation of FPV to CEF that was safe and immunogenic, with the potential for its use in the production of self-sufficiency vaccine for fowlpox prevention and control in poultry.
Intraline genomic heterogeneity of the triple-negative breast cancer MDA-MB-231 cell line
Authors: Varela-Rouco Nair , Estévez-Gómez Nuria , Fernández-Santiago Cristóbal , Tomás Laura , Pérez Miriam , García-Souto Daniel , Pasantes Juan Jose , Piñeiro Roberto , Alves João Miguel , Posada David 
Published: February 2025

SUMMARYCancer cell lines are valuable models for studying tumor biology, yet their genomic evolution during culture can compromise experimental reproducibility. We conducted a detailed genomic analysis of the triple-negative breast cancer cell line MDA-MB-231, examining sublines obtained from different sources, at various time points, and across distinct passages. We introduce the concept of intraline heterogeneity (ILH) to highlight the genomic variability observed among these sublines. Our analyses revealed extensive genomic diversity, including differences in single nucleotide variants (SNVs) and copy number alterations (CNAs). In particular, CNAs exhibited remarkable heterogeneity, with pronounced chromosomal gains and losses between sublines, underscoring the impact of genomic instability on ILH. These findings suggest that ILH may influence experimental outcomes, emphasizing the importance of considering passage-specific genomic characterization to ensure consistency and reliability in cancer research.
Single-sample, multi-omic mass spectrometry for investigating mechanisms of drug toxicity
Authors: Mahmud Iqbal , Chan Wai-Kin , Yannell Karen , Simmermaker Cate , Van de Bittner Genevieve , Wu Linfeng , Chan Daniel , Mohsin Sheher Banu , Liu Yiwei , Sausen John , Weinstein John N. , Lorenzi Philip L. 
Published: February 2025

ABSTRACTPoor therapeutic index is a principal cause of drug attrition during development. A case in point is L-asparaginase (ASNase), an enzyme-drug approved for treatment of pediatric acute lymphoblastic leukemia (ALL) but too toxic for adults. To elucidate potentially targetable mechanisms for mitigation of ASNase toxicity, we performed multi-omic profiling of the response to sub-toxic and toxic doses of ASNase in mice. We collected whole blood samples longitudinally, processed them to plasma, and extracted metabolites, lipids, and proteins from a single 20-µL plasma sample. We analyzed the extracts using multiple reaction monitoring (MRM) of 500+ water soluble metabolites, 750+ lipids, and 375 peptides on a triple quadrupole LC-MS/MS platform. Metabolites, lipids, and peptides that were modulated in a dose-dependent manner appeared to converge on antioxidation, inflammation, autophagy, and cell death pathways, prompting the hypothesis that inhibiting those pathways might decrease ASNase toxicity while preserving anticancer activity. Overall, we provide here a streamlined, three-in-one LC-MS/MS workflow for targeted metabolomics, lipidomics, and proteomics and demonstrate its ability to generate new insights into mechanisms of drug toxicity.
AAV-mediated peripheral single chain variable fragments’ administration to reduce cerebral tau in adult P301S transgenic mice: mono- vs combination therapy
Authors: Katel Sebica , Cicalo Julia , Vasciaveo Valeria , Carrion Joseph , Leann Mahadeo , Huerta Patricio T. , Marambaud Philippe , Giliberto Luca , d’Abramo Cristina 
Published: February 2025

AbstractTau is a primary target for immunotherapy in Alzheimer’s disease. Recent studies have shown the potential of anti-tau fragment antibodies in lowering pathological tau levelsin vitroandin vivo. Here, we compared the effects of single-chain variable fragments (scFv) derived from the well-characterized monoclonal antibodies PHF1 and MC1. We used adeno-associated virus 1 (AAV1) to deliver scFvs to skeletal muscle cells in eight-week-old P301S tau transgenic mice. We evaluated motor and behavioral functions at 16 and 23 weeks of age and measured misfolded, soluble, oligomeric and insoluble brain tau species. Monotherapy with scFv-MC1 improved motor and behavioral functions more effectively than scFv-PHF1 or combination therapy. Brain glucose metabolism also benefited from scFv-MC1 treatment. Surprisingly, combining scFvs targeting early (MC1) and late (PHF1) tau modifications did not produce additive or synergistic effects. These results confirm that intramuscular AAV1-mediated scFv-MC1 gene therapy holds promise as a potential treatment for Alzheimer’s disease. Our findings also suggest that combining scFvs targeting different tau epitopes may not necessarily enhance efficacy if administered together in a prevention paradigm. Further research is needed to explore whether other antibodies’ combinations and/or administration schedules could improve the efficacy of scFv-MC1 alone.Graphical abstract/eTOC synopsisKatel and colleagues show that peripheral vectorized scFvMC1 (in monotherapy) reduces pathological tau species in tau transgenic mice more efficiently than in combination with scFv-PHF1. The authors observed improved motor and behavioral functions together with increased brain glucose metabolism in scFv-MC1-treated mice.
POCALI: Prediction and insight On CAncer LncRNAs by Integrating multi-omics data with machine learning
Authors: Rao Ziyan , Wu Chenyang , Liao Yunxi , Ye Chuan , Huang Shaodong , Zhao Dongyu 
Published: February 2025

AbstractLong non-coding RNAs (lncRNAs) are receiving increasing attention as cancer markers for cancer diagnosis and treatment. Although there are many computational methods to identify cancer lncRNAs, they do not comprehensively integrate multi-omics features for predictions or systematically evaluate the contribution of each class of omics to the multifaced landscape of cancer lncRNAs. In this study, we developed an algorithm, POCALI, to identify cancer lncRNAs by integrating 44 omics features across six categories. We explored the contributions of different omics to identifying cancer lncRNAs and, more specifically, how each feature contributes to a single prediction. We also evaluated our model and benchmarked POCALI with existing methods. Finally, we validated the cancer phenotype and genomics characteristics of the novel cancer lncRNAs that were predicted. POCALI identified secondary structure and gene expression-related features as strong predictors of cancer lncRNAs, and epigenomic features as moderate predictors. POCALI performed better than other methods, especially in terms of sensitivity, and predicted more candidates. Novel POCALI-predicted cancer lncRNAs had strong relationships with cancer phenotypes, similar to known cancer lncRNAs. Overall, this study facilitated the identification of previously undetected cancer lncRNAs and the comprehensive exploration of the multifaceted feature contributions to cancer lncRNA prediction.
An RNA Splicing System that Excises Transposons from Animal mRNAs
Authors: Zhao Long-Wen , Nardone Christopher , Paulo Joao A. , Elledge Stephen J. , Kennedy Scott 
Published: February 2025

AbstractAll genomes harbor mobile genetic parasites called transposable elements (TEs). Here we describe a system, which we term SOS splicing, that protectsC. elegansand human genes from DNA transposon-mediated disruption by excising these TEs from host mRNAs. SOS splicing, which operates independently of the spliceosome, is a pattern recognition system triggered by base-pairing of inverted terminal repeat elements, which are a defining feature of the DNA transposons. We identify three factors required for SOS splicing in bothC. elegansand human cells; AKAP17A, which binds TE-containing mRNAs; the RNA ligase RTCB; and CAAP1, which bridges RTCB and AKAP17A, allowing RTCB to ligate mRNA fragments generated by TE excision. We propose that SOS splicing is a novel, conserved, and RNA structure-directed mode of mRNA splicing and that one function of SOS splicing is to genetically buffer animals from the deleterious effects of TE-mediated gene perturbation.
Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC
Authors: Conrad Daniel N. , Phong Kiet T. , Korotkevich Ekaterina , McGinnis Christopher S. , Zhu Qin , Chow Eric D. , Gartner Zev J. 
Published: February 2025

AbstractLarge-scale scATAC-seq experiments are challenging because of their costs, lengthy protocols, and confounding batch effects. Several sample multiplexing technologies aim to address these challenges, but do not remove batch effects introduced when performing transposition reactions in parallel. We demonstrate that sample-to-sample variability in nuclei-to-Tn5 ratios is a major cause of batch effects and develop MULTI-ATAC, a multiplexing method that pools samples prior to transposition, as a solution. MULTI-ATAC provides high accuracy in sample classification and doublet detection while eliminating batch effects associated with variable nucleus-to-Tn5 ratio. We illustrate the power of MULTI-ATAC by performing a 96-plex multiomic drug assay targeting epigenetic remodelers in a model of primary immune cell activation, uncovering tens of thousands of drug-responsive chromatin regions, cell-type specific effects, and potent differences between matched inhibitors and degraders. MULTI-ATAC therefore enables batch-free and scalable scATAC-seq workflows, providing deeper insights into complex biological processes and potential therapeutic targets.