bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic dysregulation of metabolic programs mediates liposarcoma cell plasticity
Authors: Pimenta Erica M. , Garza Amanda E. , Camp Sabrina Y. , Park Jihye , Hoffman Samantha E. , Valderrábano Laura , Fu Jingxin , Bi Kevin , Karam Julie , Titchen Breanna M. , Khandekar Melin J. , Shannon Erin , Kang Yun Jee , Nag Anwesha , Thorner Aaron R. , Raut Chandrajit P. , Hornick Jason L. , Merriam Priscilla , Solimini Nicole L. , George Suzanne , Demetri George D. , Van Allen Eliezer M. 
Published: January 2025

ABSTRACTSarcomas are rare connective tissue cancers thought to arise from aberrant mesenchymal stem cell (MSC) differentiation. Liposarcoma (LPS) holds valuable insights into dysfunctional differentiation given its well- and dedifferentiated histologic subtypes (WDLPS, DDLPS). Despite well-established differences in histology and clinical behavior, the molecular pathways underlying each subtype are poorly understood. Here, we performed single-nucleus multiome sequencing and spatial profiling on carefully curated human LPS samples and found defects in adipocyte-specific differentiation within LPS. Loss of insulin-like growth factor 1 (IGF1) and gain of cellular programs related to early mesenchymal development and glucagon-like peptide-1 (GLP-1)-induced insulin secretion are primary features of DDLPS. IGF1 loss was associated with worse overall survival in LPS patients. Throughin vitrostimulation of the IGF1 pathway, we identified that DDLPS cells are deficient in the adipose-specific PPARG isoform 2 (PPARG2). Defects in IGF1/PPARG2 signaling in DDLPS led to a block in differentiation that could not be fully overcome with the addition of exogenous IGF1 or the pro-adipogenic agonists to PPARG and GLP-1. However, we noted upregulation of the IGF1 receptor (IGF1R) in the setting of IGF1 deficiency, which promoted sensitivity to an IGF1R-targeted antibody-drug conjugate that may serve as a novel therapeutic strategy in LPS. In summary, lineage-specific defects in adipogenesis drive dedifferentiation in LPS and may translate into selective therapeutic targeting in this disease.
Comparative spatial transcriptomics of hair follicle-T cell interactions in mouse, dog and human reveals conserved drivers of primary cicatricial alopecia
Authors: Yıldız-Altay Ümmügülsüm , Adhanom Rutha , Abdi Warda , Romasco Andrew , You Lauren , Santacruz Elise , Shakiba Saeed , Daga Mridushi , Tang Qi , Olivera Matthew , Cicuto Thomas , Bretheau Floriane , Baer Christina , Arjomandnejad Motahareh , Keeler Allison , Bui Helen , Shokrani Babak , Almela Ramon , Byrd Angel S. , Frey Cheri , Richmond Jillian M. 
Published: January 2025

AbstractPrimary cicatricial alopecias (PCA) encompass several autoimmune disorders characterized by scarring hair loss. Many of these conditions are lymphocytic and are thought to be driven by T cell populations. Here, we sought to characterize potential T cell-hair follicle communication pathways in the microanatomical niche using spatial transcriptomics across 3 mammalian species including a novel mouse model, spontaneous disease in companion dogs and human archival diagnostic biopsies. Flow cytometry of mouse model skin confirmed loss of CD34+ bulge cells and keratinocytes, and bulk microarray and histology revealed expression of collagens and development of fibrosis.In vivoear imaging in mice engrafted with Kikume photoconvertible OT1 CD8+ T cells confirmed long-lived RFP+ T cells in skin arrest near hair follicles and recruit other GFP+ T cells. OT1 T cells expressed CD69, CD103, CD122 and CD62L, which is a binding partner of CD34. Digital spatial profiling using CD3, CD8 and CD45 cell masking identified CXCR3 ligands and IFN response genes in hair follicles, and “metabolic” pathways in T cells, which were also recapitulated in dog and human biopsies. Bulk human RNA as well as spatial analysis of perifollicular T cells confirmed enrichment ofCD69andSELL/CD62L. Different pathways predominated in other CD3+ regions of interest in CD4+ driven conditions including mucocutaneous lupus erythematosus and subacute cutaneous lupus erythematosus. Last, we identify novel drug-targetable pathways, namelyCFDandS100A8/9, that could be further explored to disrupt processes in these conditions through veterinary and human trials.
WASTER: Practicalde novophylogenomics from low-coverage short reads
Authors: Zhang Chao , Nielsen Rasmus 
Published: January 2025

AbstractThe advent of affordable whole-genome sequencing has spurred numerous large-scale projects aimed at inferring the tree of life, yet achieving a complete species-level phylogeny remains a distant goal due to significant costs and computational demands. Traditional species tree inference methods, though effective, are hampered by the need for high-coverage sequencing, high-quality genomic alignments, and extensive computational resources. To address these challenges, this study introduces WASTER, a novelde novotool for inferring species trees directly from short-read sequences. WASTER employs a k-mer based approach for identifying variable sites, circumventing the need for genome assembly and alignment. Using simulations, we demonstrate that WASTER achieves accuracy comparable to that of traditional alignment-based methods, even for low sequencing depth, and has substantially higher accuracy than other alignment-free methods. We validate WASTER’s efficacy on real data, where it accurately reconstructs phylogenies of eukaryotic species with as low depth as 1.5X. WASTER provides a fast and efficient solution for phylogeny estimation in cases where genome assembly and/or alignment may bias analyses or is challenging, for example due to low sequencing depth. It also provides a method for generating guide trees for tree-based alignment algorithms. WASTER’s ability to accurately estimate trees from low-coverage sequencing data without relying on assembly and alignment will lead to substantially reduced sequencing and computational costs in phylogenomic projects.
Cell-cultured PDMS vascular model to allow placement of implant devices
Authors: Okuno Taku , Ito Kazuyo , Funamoto Kenichi , Yoshino Daisuke 
Published: January 2025

AbstractBackgroundA stent maintains normal blood flow by expanding a stenotic artery from the inside. Stents currently in clinical use are mechanically sub-optimized and, therefore, exert excessive mechanical stimuli on the vascular wall. This can lead to arterial inflammation and potentially in-stent restenosis. To optimize the force exerted by a stent on the vascular wall, we should understand, reproduce, and analyze in detail the mechanical field to which the stented vessel is exposed. However, to date, noin vitromodel has been established that can adequately evaluate the mechanical effects of a stent on the vascular wall and be constructed without relying on a laboratory’s know-how. This study aims to develop a three-dimensionalin vitrovascular model that allows stent placement and to provide the details of its construction method.MethodsPolydimethylsiloxane (PDMS) was used to mimic the adventitial structure of arteries. Human carotid artery endothelial cells (HCtAECs) were then seeded on the luminal surface and cultured for 24 h to form a confluent monolayer (intima). The constructed model was installed in the flow-exposure culturing system, and hemodynamic stimulation (two types of shear stress (SS); 0.5 Pa and 2.3 Pa) was applied to the HCtAECs inside to reproduce the physiological state of blood vessels. In addition, a self-expanding stent was placed in the model during perfusion culture.ResultsWe examined the performance of the developed model based on quantitative evaluations of endothelial morphology in response to SS and in-stent endothelialization. Exposure to SS for 24 and 48 h caused endothelial orientation and elongation in the direction of flow, confirming the physiological responses of blood vessels. We were also able to quantitatively evaluate endothelial migration (endothelialization) to the stent.DiscussionOur model can reproduce the mechanical field inside the stented blood vessel, including hemodynamic stimuli. Based on the results obtained, the developed cell-cultured vascular model has sufficient performance to be used not only for quantitative evaluation of in-stent endothelialization but also for optimization of the mechanical fields in the stented vessel.
Cell type-specific eQTL detection from single-cell RNA-seq reveals post-transcriptional regulatory mechanisms in human islets
Authors: de Winter Twan J.J. , Sovrovic Miha , Dekker Esmée , de Graaf Natascha , Sun Han , Johnson James D. , MacDonald Patrick E. , Gloyn Anna L. , Carlotti Françoise , de Koning Eelco J.P. , Alemany Anna 
Published: January 2025

AbstractGene regulatory networks (GRN) must be robust to maintain cellular identity across individuals yet flexible to accommodate population genetic variants. Therefore, comparing expression quantitative trait loci (eQTL) in health and disease can reveal hidden players in GRN and post-transcriptional regulation. Here, we developed a computational pipeline to investigate the gain and loss of eQTLs in the 3’ untranslated region of genes using single-cell RNA sequencing. We repurposed datasets from human islets of donors with and without type 2 diabetes (T2D), and found that beta cells lose identity by gaining alpha cell-specific eQTLs in T2D. By integrating the eQTL landscape with islet miRNA expression, we inferred miRNA-mediated gene regulation in islets. Further validation of miR-127-5p targetingPTENmRNA revealed its association with EGFR signaling and insulin secretion. Hence, our pipeline provides a flexible framework to unravel post-transcriptional regulatory mechanisms in health and disease with cell type resolution.
Single-cell differential detergent fractionation for detection of cytokeratin 8 proteoforms
Authors: Khartchenko Anna Fomitcheva , Lam Trinh , Herr Amy E. 
Published: January 2025

ABSTRACTSimultaneous profiling of proteoforms and nucleic acids at the single-cell level, i.e., multi omics, directly links the central dogma. However, current single-cell approaches are limited in their ability to identify proteoforms while preserving the nucleus for further analysis. This limitation is especially pronounced in proteins where their proteoforms present diverse biological functions such as cytokeratin 8 (CK8), which, while commonly known for its structural role, is also involved in several diseases. Here, we present a single-cell western blot (scWB) integrated with differential detergent fractionation (DDF) to selectively solubilize and separate CK8 proteoforms while preserving nuclear integrity for subsequent nucleus-based assays. We report on assay development, including screening a panel of lysis buffers based on nonionic detergents and electrophoresis conditions to achieve a separation resolution between two proteoforms of up to 0.94 with an electric field of 30 V/cm, while preserving an intact nucleus. The cytoplasm-specific lysis approach (DDF buffer) demonstrated comparable solubilization efficiency to whole-cell solubilization (RIPA buffer), achieving proteoform solubilization in 14.3% and 10.3% of solubilized cells using DDF and RIPA buffers, respectively, while keeping the nucleus intact. To understand the broad applicability of the assay conditions, we scrutinized electrophoresis performance for resolving CK8 proteoforms across a panel of widely used breast cancer cell lines (MCF7, SKBR3, and MDA-MB-231), showing presence of proteoforms only in MCF7. Our approach allows for tailored solubilization, achieving reliable proteoform detection and nuclear retention across different cell types. Proteoform profiling at the single-cell level forms a basis for the exploration of the role of specific CK8 molecular forms in cellular processes.
LEVERAGING TRANSFER LEARNING FOR HIGH-ACCURACY PHENOTYPIC SCREENING IN ZEBRAFISH IMAGE ANALYSIS
Authors: Jayaraman Varshini Uma , Medishetti Raghavender , Ghosh Shreetama , Chatti Kiranam , Uppada Mahesh Kumar , Oruganti Srinivas 
Published: January 2025

ABSTRACTThis paper presents a method for classifying zebrafish images captured before and after drug administration. Leveraging the power of transfer learning and fine-tuning, the approach effectively overcomes the challenges of limited datasets in biomedical imaging. By employing a pre-trained convolutional neural network (CNN) as the base model, transfer learning allows us to utilize learned features from large-scale image datasets, significantly reducing training time and computational resources. Fine-tuning specific layers of the model on our zebrafish dataset further enhances its ability to detect subtle visual differences induced by drug administration. The proposed approach achieves high accuracy in classifying zebrafish images, demonstrating its potential as a reliable tool for analysing phenotypic changes due to pharmacological interventions. This model could be instrumental in accelerating drug discovery and research in zebrafish-based assays, offering a scalable and efficient solution for image-based biomedical analysis.
Genomic reconstruction ofBacillus anthracisfrom complex environmental samples enables high throughput identification and lineage assignment in Pakistan
Authors: Podowski Justin C , Forrester Sara , Yaqub Tahir , Aqel Amin , Abu-Lubad Mohammad , Mukhtar Nadia , Aziz Muhammad Waqar , Sardar Nageen , Bin Aslam Hassaan , Pervaiz Hamda , Wolfe Alan J , Schabacker Daniel S 
Published: January 2025

AbstractBacillus anthracis, the causative agent of anthrax, is a highly virulent zoonotic pathogen primarily affecting domesticated and wild herbivores. Human exposure toB. anthracisis primarily through contact with infected animals or contaminated animal products. In Pakistan, where livestock vaccines are largely unavailable and infected carcasses are often disposed of improperly, the risk to humans, wildlife and livestock is significant. Currently, diagnosis of anthrax infections and outbreak tracing necessitates the isolation and culturing ofB. anthracis, a process that requires BSL-3 facilities. In this study, we show that positive identification, genome reconstruction and lineage assignment can be accomplished using bioinformatic analysis of DNA extracted directly from environmental samples that would otherwise provide the starting material for isolation and culturing. This approach does not require laboratory target enrichment as is necessary for other pathogens, due in part to the extremely high bacterial load in the bloodstream in the deceased animals. Using these methods, we greatly expand the knowledge of endemicB. anthracisin Pakistan. We provide the first referenceB. anthracisgenomes from Pakistan since the 1970s and identify A.Br.014 Aust94 as a minor circulating sublineage alongside dominant A.Br.047 Vollum. Future work will focus on limits of detection and will determine if this bioinformatic method can be expanded more broadly forB. anthracisor other pathogens to replace typical culture-based methods.
Investigating the role of stomatal dynamics on agronomic traits using aslac1-2 Zea maysmutant
Authors: Twohey Robert J. , Christenson Clay G. , Li Catherine , Bacher Harel , Calleja Sebastian , Pastor Bryan , Hanneman Marjorie , Wickes-Do Liam , Gore Michael A. , Pauli Duke , Moose Stephen P. , Studer Anthony J. 
Published: January 2025

AbstractThe production of staple food crops is becoming increasingly difficult due to the amount of freshwater needed to realize food security for a growing global population. Climate projections show hotter and drier growing seasons in traditionally productive agricultural regions, which will increase the demand for limited water resources. Thus, strategies to improve water use efficiency will only become more important for sustainable agriculture. At the leaf level, stomatal conductance has a large influence on transpirational water loss and therefore water use efficiency. The anion channel SLAC1 has been shown in several plant species to function as the primary mechanism for stomatal closure, which allows stomatal aperture to change dynamically in response to environmental stimuli. Given thatslac1is a single gene that can significantly alter stomatal conductance, it has the potential to serve as a control point for improving water use efficiency. Here we fully characterize aZea mays slac1-2mutant in multiple field environments. Interestingly, homozygousslac1-2hybrids did not show improved net CO2assimilation or increased grain yield despite having greater stomatal conductance compared to a wild-type hybrid. Net CO2assimilation and grain yield were either lower or similar inslac1-2compared to wild-type across environments. Furthermore, theslac1-2hybrid did not have increased nitrogen uptake. These results suggest that the C4carbon concentrating mechanism removes any stomatal conductance limitations to CO2assimilation, even in highly productive wild-typeZ. mayshybrids. Because theslac1-2hybrids eliminate stomatal conductance as a major variable for modulating water loss, future studies will be able to investigate alternate regulators of plant water potential to identify novel mechanisms for increasing water use efficiency.
Risk factors for renal stone development in adults with primary hyperparathyroidism: A protocol for a systematic review and meta-analysis
Authors: Jay Mohammad , Andrei Sorina , Hoang Peter , Samhat Hussein , Jones Roland , Fu Rui , Lipscombe Lorraine , Eskander Antoine 
Published: January 2025

AbstractBackgroundPrimary hyperparathyroidism (PHPT) is characterized by overactive parathyroid glands. Renal stones (RS) are a common complication of PHPT and is associated with increased morbidity. However, the risk factors for RS in PHPT are not well-established and the latest international PHPT guideline highlights the need for further research into this area.ObjectiveWe aim to summarize and meta-analyze the existing evidence on prespecified risk factors associated with RS in adults with PHPT.Methods and AnalysisWe will search MEDLINE, EMBASE, and Cochrane Central from inception. Two independent reviewers will screen studies and include prospective/retrospective cohort, case-control, and cross-sectional designs in adults (≥18 years) with PHPT. Randomized trials, conference abstracts, case reports, and commentaries will be excluded. Two reviewers will independently extract data on population characteristics, risk factors, RS outcomes, and assess risk of bias using the Quality in Prognostic Studies tool. A random-effects model will be used to pool odds ratios. We will separately pool adjusted (primary analyses) and unadjusted odds ratios (secondary analyses) with their corresponding 95% confidence intervals. Certainty will be evaluated with the Grading of Recommendations Assessment, Development, and Evaluation framework. Heterogeneity will be assessed using the I² statistic and publication bias will be evaluated with funnel plots.DiscussionEarly identification of patients with PHPT at high risk for RS can facilitate the implementation of preventive strategies and reduce morbidity. Furthermore, recognizing these risk factors can assist clinicians in prioritizing treatment for those at higher risk, ultimately improving patient outcomes.Protocol registrationThe protocol was registered in PROSPERO on November 14, 2024 (registration ID: CRD42024608180).FundingNo source of financial funding was used.
Evidence of Resiliency in Maternal Health Services and Outcomes in Kono District, Sierra Leone during the COVID-19 Pandemic: An Observational Study
Authors: Boima Foday , Mekonnen Zeleke Abebaw , Koroma Manso M , Lado Marta , Chan Adrienne K. , Mishra Sharmistha , N’jai Alhaji U. , Molleh Bailah , Sevalie Stephen , Lakoh Sulaiman 
Published: January 2025

AbstractBackgroundThis study evaluated the resilience and outcomes of maternal health services during the COVID-19 pandemic in two health facilities in eastern Sierra Leone. Its aims to describe the use of maternal healthcare services and maternal and neonatal outcomes in these two facilities before, during, and after the COVID-19 pandemic.MethodsThe study involved analysis of routine programme data (March 2019 to February 2022) from two public-funded health facilities supported by a non-governmental organization (Partners In Health in Sierra Leone): Koidu Government Hospital and Wellbody Clinic. Aggregated and de-identified secondary data from the Partner In Health Maternal Health Database was abstracted using a standardized tool. Descriptive statistics and bivariable negative binomial regression were used to assess the association between time periods (before COVID-19 [March 2019 to February 2020], during COVID-19 emergency [March 2020 to February 2021], after COVID-19 emergency [March 2021 to February 2022) and outcomes each month (fourth antenatal care visit and facility deliveries).ResultsThe study analyzed 3,204 fourth antenatal care visits and 7,369 deliveries over 36 months at both health facilities. Fourth antenatal care visits (from 947 to 920) and facility deliveries (from 2309 to 2221) decreased during COVID-19 compared to pre-COVID-19. However, maternal (from 32 to 23) and neonatal (36 to 26) deaths declined during COVID-19 compared to the pre-COVID-19 period at Koidu Government Hospital.ConclusionIn Sierra Leone, the resources and efforts directed to the post-Ebola recovery strategy were tested during and after the COVID-19 pandemic. Our study demonstrates the resilience of maternal and neonatal services in two healthcare facilities in a less-affected region of Sierra Leone, to the anticipated disruptions due to the COVID-19 pandemic.
X-Pro: A web-based tool to analyze the loss and gain of local interaction upon a point mutation on protein structures
Authors: Viswakarma Aman , Neelakanteswara Anurag , Thiyagarajan Saravanamuthu 
Published: January 2025

AbstractUnderstanding how point mutations affect protein structures is critical for understanding their impacts on a protein’s function and, eventually their role in causing diseases or biological differences. In recent decades, structural inferences of missense mutations have gained significant attention due to their importance in understanding monogenic disorders. Making point mutations in silico is one of the simple bioinformatics tasks. Existing GUI-based open-source tools like PyMOL, Chimera, Discovery Studio, etc., have simplified this task so that it can be done with a few mouse clicks. However, this continues to be a difficult task for untrained biologists. Further, understanding the loss and gain of interactions caused by such mutations remains even more challenging to them. To address this, we have developed a simple web-browser-based application namedX-Prowherein a PDB structure, chain ID, residue number, and the target mutation are taken as inputs, along with mutation information. The tool runs PyMOL and LigPlot tools in the back-end, taking the site of mutation as the ligand and returning graphical images of the structure before and after in-silico point mutation, and a table listing the loss and gain of interactions arising from this mutation. The tool is available for users at the URLhttp://bts.ibab.ac.in/X-Pro.php.