bluuebunny/crossref_metadata_2025_split huggingface dataset:
The COVID‐19 vaccine ChAdOx1 is opsonized by anti‐vector antibodies that activate complement and promote viral vector phagocytosis
Authors: Nissilä Eija , Starck Leo , Aho Elias , Venerandi Erika , Jalkanen Pinja , Leskinen Katarzyna , Uvarov Pavel , Saavalainen Päivi , Julkunen Ilkka , Kotimaa Juha , Haapasalo Karita , Meri Seppo 
Published: February 2025

AbstractThe ChAdOx1 nCoV‐19 vaccine has been in large‐scale use during the COVID‐19 pandemic. Limited efficacy compared to mRNA vaccines and certain potential side effects raise the question of whether anti‐adenoviral vector antibodies influence immune responses against the vaccine. Complement activation by ChAdOx1 and leukocyte phagocytosis of ChAdOx1 in vitro were studied. Plasma IgG levels against ChAdOx1 and human adenovirus 2 (hAdV2) hexon protein were determined (n = 20) and IgGs from high‐ and low‐titre plasmas were isolated (n = 3). Complement activation was measured as cleavage of C3 by immunoblotting and generation of C3a and sC5b‐9 by ELISA. pHrodo‐labelled ChAdOx1 was opsonized with complement and IgG, and phagocytosis by isolated blood PMNs in vitro was studied by flow cytometry. The transcriptomic profile of PMN cells exposed to ChAdOx1 was analysed by RNA‐seq. ChAdOx1 activated the classical complement pathway in an anti‐adenovirus antibody‐dependent manner. Generation of the terminal complement complex sC5b‐9 in individual sera correlated with anti‐hAdV2 hexon and anti‐ChAdOx1 IgG levels. Phagocytosis of ChAdOx1 also correlated significantly with anti‐hAdV2 hexon IgG, anti‐ChAdOx1 IgG and serum sC5b‐9 levels. High‐titre anti‐hAdv2 hexon IgG increased phagocytosis in the presence of normal serum. Anti‐vector antibodies induced rapid complement activation and promoted phagocytosis of the ChAdOx1 vaccine by neutrophils. Moreover, transcriptomic analysis revealed upregulation of complement‐related genes induced by the ChAdOx1 vaccine in vitro. Anti‐adenovirus vector antibodies and complement activation may thus influence the efficacy of the ChAdOx1 vaccine against SARS‐CoV‐2 and be also involved in vaccine‐related side effects.
Here's another nice mess you've gotten us into1
Authors: Thrift Nigel 
Published: February 2025

AbstractThe British university system, like the systems in a number of other countries, is being transformed as it grows in size and function into a set of industrial combines that power a process of mass production which is both downgrading the role of academics and threatening the production of creative work. I enumerate some of the reasons why this is happening, including questionable government policies, a tangle of over‐regulation and apparent management quiescence, and consider what might be done to reinvent a system which is, quite frankly, an overly bureaucratic mess. To right the system, I pose a series of questions that urgently need constructive answers. As the creative core of the university, many of these answers need the contribution of academics—and, it might be argued, as a matter of right. But it is a measure of how far the system has gone in the wrong direction that this isn't happening. They have been supplanted by policy‐making forces for whom their interests are rarely central. That must surely change.
Impact of suture materials polydioxanone and poliglecaprone 25 on non‐infected clean orthopedic stifle procedure incisional dehiscence rates
Authors: Caiazzo Megan N. , Cortina Brittany L. , Terreros Alex , Daye R. Mark 
Published: February 2025

AbstractObjectiveTo compare dehiscence rates, and evaluate incisional outcome, between the use of polydioxanone (PDS) versus poliglecaprone 25 (Monocryl) suture for skin closure in dogs undergoing a variety of clean orthopedic procedures associated with the stifle.Study designRandomized, prospective, cross‐sectional design.AnimalsClient owned dogs with cranial cruciate disease deemed appropriate surgical candidates for tibial plateau leveling osteotomy (TPLO) or other clean orthopedic stifle procedure (N = 232).MethodsDogs undergoing a TPLO, or other clean orthopedic procedure were randomly assigned to one of three groups using different closure materials. Incisional dehiscence rate in the absence of infection was analyzed against multiple variables. Infection and dehiscence were characterized based on previously published descriptions.ResultsA total of 232 dogs were analyzed with 72 in Group 1, 85 in Group 2, and 75 in Group 3. A total of 137/232 (59.05%) of dogs received postoperative antibiotics. Overall, 22/232 (9.48%) of dogs showed dehiscence without evidence of infection during the follow up period. Postoperative antibiotic use (p = .023) and signs of infection (p < .001) were statistically different between the healed and dehisced groups. The mean weight, body condition score, and incision length were not different between groups.ConclusionThere is no difference in dehiscence rate in the absence of infection following a clean orthopedic procedure when comparing skin closure with PDS versus Monocryl.Clinical significanceEither PDS or Monocryl may be used for skin closure following a clean orthopedic procedure.
Increased muscle satellite cell content and preserved telomere length in response to combined exercise training in patients with FSHD
Authors: Horwath Oscar , Montiel‐Rojas Diego , Ponsot Elodie , Féasson Léonard , Kadi Fawzi 
Published: February 2025

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is an inherited muscle disease characterized by weakness and muscle wasting. In the absence of available treatments, exercise training has emerged as a potential strategy to attenuate muscle tissue deterioration. However, little is known about the impact of chronic exercise on degenerative events and regenerative capacity in FSHD muscle. Muscle biopsies were obtained from 16 FSHD patients before and after a 24 week training program combining aerobic‐, strength‐ and high‐intensity exercise (Control; n = 8, Training; n = 8). Histochemical and immunohistochemical approaches were applied to assess histopathological signs, markers of regeneration, inflammatory infiltrates and satellite cell content. Muscle telomere length was measured as an indicator of the remaining regenerative capacity. The proportion of muscle fibres expressing developmental myosins and centralized myonuclei was not exacerbated after the intervention. Similarly, no alterations were observed in the number of inflammatory infiltrates (CD68+ cells). Alongside muscle hypertrophy in slow (P = 0.022) and fast fibres (P = 0.022 and P = 0.008), satellite cell content increased specifically in fast fibres (+75 %, P = 0.015), indicating a functional satellite cell pool in FSHD muscle. Importantly, exercise training was not associated with a shortening of muscle telomere length, suggesting that muscle cell turnover was not accelerated despite an expansion of the satellite cell pool. Our findings suggest that combined exercise training elicits beneficial muscular adaptations without impairing important indicators of skeletal muscle regenerative capacity in patients with FSHD.
imageKey points
A 24 week combined exercise training program is a safe and well‐tolerated strategy to attenuate skeletal muscle deterioration in facioscapulohumeral muscular dystrophy (FSHD) patients.
Markers of histopathology, muscle fibre regeneration and inflammatory infiltrates were not exacerbated following exercise training in FSHD muscle.
Here, we show novel data that exercise training in FSHD patients induced muscle fibre hypertrophy and triggered an expansion of the satellite cell pool specifically in fast fibres.
Exercise training in these patients is not associated with a shortening of muscle telomere length thereby indicating a preserved capacity for muscle regeneration.
Exploring the Connection Between Brain Strain and Cognitive Changes: A Protocol Study
Authors: Menghani Ritika Raj , Bardall Clayton , Tanaka Martin L. , Kraft Reuben H. 
Published: February 2025

Abstract
Given the rise of head injury in the youth, much focus has been directed toward predicting brain injury using simulation tools such as finite element analysis. Various brain strain measures are proposed as indicators of concussion. However, the clinical connection between brain strain and cognitive changes has not been fully established. In this study, we develop a framework to compare strains and other metrics obtained from finite element brain simulations with sideline cognitive testing results. We conducted a preliminary study for ten college football players. The players were equipped with custom fit mouthguards and were monitored for one season. A total of 2185 impacts were collected, and eight cognitive tests were conducted that were triggered when acceleration measurement exceed a threshold of 30Gs. Axonal injury metrics were examined while considering cognitive scores. This study represents a protocol investigation with preliminary findings, as it explores the correlation between brain strain metrics and cognitive deficits in a sample of ten football players over one season.
Benchmarking $$\mathbf {\Lambda }$$NN three-body forces and first predictions for $$A=3-5$$ hypernuclei
Authors: Le Hoai , Haidenbauer Johann , Kamada Hiroyuki , Kohno Michio , Meißner Ulf-G. , Miyagawa Kazuya , Nogga Andreas 
Published: February 2025

Abstract
Explicit expressions for the leading chiral hyperon-nucleon-nucleon three-body forces have been derived by Petschauer et al (Phys Rev C93:014001, 2016). An important prerequisite for including these three-body forces in few- and many-body calculations is the accuracy and efficiency of their partial-wave decomposition. A careful benchmark of the

$$\Lambda $$

Λ

NN potential matrix elements, computed using two robust and efficient partial-wave decomposition methods, is presented. In addition, results of a first quantitative assessment for the contributions of

$${\Lambda }$$

Λ

NN forces to the separation energies in

$$A=3-5$$

A
=
3
-
5

hypernuclei are reported.
In Search of Representative Translational Cancer Model Systems
Authors: Trembath Hannah E. , Spanheimer Philip M. 
Published: February 2025

Racial disparities in cancer outcomes are well documented across tumor types. For patients with breast cancer, Black women are more likely to present with more aggressive molecular features and more likely to die from disease, even after accounting for those features. Recent efforts have been aimed at developing translational model systems for precision medicine strategies, and a major focus has been on patient-derived organoids. Organoids allow for robust in vitro experimental platforms, including drug and CRISPR screens while maintaining more complex cancer and tumor microenvironment subpopulations than cell lines. For results that are broadly translationally relevant, it is important that cancer models are derived from the spectrum of human disease and humans with disease. In this issue of Cancer Research, Madorsky Rowdo and colleagues derive breast cancer organoids from patients with African ancestry and use CRISPR-Cas9 screens to identify novel therapeutic vulnerabilities. These findings demonstrate the promise of representative cancer model systems to facilitate discoveries that are most likely to translate to improved therapy for all patients.
See related article by Madorsky Rowdo et al., p. 551
Abstract A019: CRISPR-based investigation of CHIP mutations reveals their role in CAR-T therapy-related inflammatory toxicities
Authors: Wang Xiuli , Goldsmith Scott R. , Rhee June-Wha , Forman Stephen J. , Zhang Chunyan , Armenian Saro 
Published: February 2025

Abstract
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by somatic mutations (e.g. DNMT3A, TET2, and ASXL1I) in hematopoietic stem cells, and linked to age-related clonal expansions and inflammatory states. We previously showed that patients with CHIP receiving CAR-T cell therapy have a four-fold risk of developing clinically significant cytokine release syndrome (CRS) compared to those without CHIP (Transplant Cell Ther 2024). This prompted us to investigate the mechanisms through which CHIP mutations could contribute to CAR-T-related toxicities. Methods: We employed CRISPR-based gene editing to target CHIP-associated genes—DNMT3A, TET2, and ASXL1—in M1-like macrophages, which were differentiated from human monocytes in the presence of 20 ng/mL of GM-CSF. Gene perturbation was achieved with cell-penetrating phosphorothioated single-stranded DNA oligonucleotides to deliver the CRISPR-Cas9 and gRNA complex (PS-Cas9/gRNA). Editing was performed using multiple gRNAs for each gene: DNMT3A (2 gRNAs), TET2 (3 gRNAs), and ASXL1 (2 gRNAs), and decreased protein expression was confirmed post-editing. We co-cultured CS1 CAR-T cells targeting multiple myeloma (MM), MM.1S cells, and edited autologous macrophages at a 1:1:0.1 ratio for 24 hours to assess the inflammatory response. Cytokine secretion was quantified using the LEGENDplex™ Human Inflammation Panel 1 (13-plex). Results: Compared to non-edited macrophages, DNMT3A-, TET2-, and ASXL1-edited macrophages consistently secreted significantly higher levels of IL-6 (642, 920, 1338 pg/ml vs. 325 pg/ml respectively, P&lt;0.05-0.001), MCP-1(90, 122, 151 pg/ml vs. 55 pg/ml, respectively, P&lt;0.01-0.001), TNFα (2015, 1722, 1874 pg/ml vs. 1043 pg/ml, respectively P:ns - &lt; 0.001), IL-1β (75, 99, 146 pg/ml vs. 38 pg/ml, respectively, P&lt;0.05-0.001), and IL-8 (21, 19, 22 ng/ml vs. 15 ng/ml, respectively, P:ns- &lt;0.001). Conclusions: These findings suggest CHIP mutations in human macrophages may exacerbate the inflammatory response in CAR-T therapy, highlighting a potential biomarker for stratifying patients at higher risk for toxicities such as CRS and guiding more personalized prophylactic interventions.
Citation Format: Xiuli Wang, Scott R. Goldsmith, June-Wha Rhee, Stephen J. Forman, Chunyan Zhang, Saro Armenian. CRISPR-based investigation of CHIP mutations reveals their role in CAR-T therapy-related inflammatory toxicities [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr A019.
Abstract B007: Epigenetic reactivation of transposable elements as prognostic markers for PD1/PDL1 immunotherapy in cancer
Authors: Wu Yixin , Wang Ting , Liang Yonghao 
Published: February 2025

Abstract
Transposable elements (TEs), once considered as "junk" DNA, are now recognized for their epigenetic and regulatory influence, especially in cancer. Cryptic regulatory elements within TEs can be epigenetically reactivated in cancer, contributing to oncogenesis and altering gene expression patterns. This reactivation results in TE-derived transcripts, which have the potential to be translated and form neoantigens that can be presented by the human leukocyte antigens (HLA) complex and recognized by T cells, ultimately impacting the tumor immune response. In this study, we analyzed RNA-seq data from melanoma patients undergoing PD1/PDL1 immunotherapy. By identifying tumor specific TE-derived transcripts and utilizing in silico translation, we detected TE-derived neoantigens in patients with differing responses to immunotherapy. Our findings indicate that the number of TE-derived neoantigens is correlated with patients' response to immunotherapy, with a higher number of neoantigens observed in patients who responded to treatment compared to those who did not. These results imply that TE-derived neoantigens may serve as potential biomarkers for predicting the prognosis of PD1/PDL1 immunotherapy treatment. Incorporating TE-derived neoantigen profiles into clinical decision-making could enhance patient selection for immunotherapy, thereby improving treatment outcomes.
Citation Format: Yixin Wu, Ting Wang, Yonghao Liang. Epigenetic reactivation of transposable elements as prognostic markers for PD1/PDL1 immunotherapy in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B007.
Abstract B013: Gene-body DNA methylation of ONECUT2 predicts its expression status and prostate cancer aggressiveness in clinic specimens
Authors: Liang Gangning , Liang Gangning 
Published: February 2025

Abstract
ONECUT2 is a lineage plasticity driver and therapeutic target in aggressive prostate cancer (PCa). The goal of this study was to determine the role of ONECUT2 gene-body DNA methylation in regulating its expression and to evaluate its potential as a biomarker and therapeutic target for aggressive PCa. We observed a robust positive correlation between ONECUT2 expression levels and gene-body DNA methylation. This role was confirmed in prostate cancer cells through treatment with a DNA methylation inhibitor (DNMTi). Targeted bisulfite sequencing was performed to measure ONECUT2 gene-body DNA methylation in 208 needle biopsies from PCa patients, revealing a correlation between ONECUT2 gene-body hypermethylation and aggressive features. Thus, measuring ONECUT2 gene-body DNA methylation in clinical specimens can provide a predictive assessment of disease progression before surgery. Our results also suggest that downregulating ONECUT2 expression using DNMTi may be a viable therapeutic strategy for treating aggressive PCa.
Citation Format: Gangning Liang, Gangning Liang. Gene-body DNA methylation of ONECUT2 predicts its expression status and prostate cancer aggressiveness in clinic specimens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B013.
Abstract B027: Modeling age-related DNA methylation changes with intestinal organoids
Authors: Vaidya Himani , Calendo Gennaro , Pompetti Anthomy , Balch Curt , Keith Kelsey , Mazdo Jozef , Jelinek Jaroslav , Issa Jean-Pierre 
Published: February 2025

Abstract
Intestinal organoids, three-dimensional cultures from intestinal stem cells, are a potential model for studying aging. DNA methylation can serve as biological clock of aging, and we hypothesized that organoid DNA methylation could be a valuable tool for aging research. We compared DNA methylation in organoids to that seen in primary aging intestinal epithelium. Genome wide, we found very substantial DNA methylation changes during organoid establishment and culture, with 27% of total CpG sites undergoing loss of methylation (hypomethylation), and 11% gaining methylation (hypermethylation). The observed hypermethylation primarily affected CpG islands and corresponded to CpG sites susceptible to age-related methylation in-vivo (p &lt; 0.001 compared to unchanged sites). Early-passage (P0 and P2) organoids derived from 4- and 24-month-old mice, preserved aging-specific methylation patterns, with a correlation coefficient of 0.48 (p &lt; 0.001) between methylation differences in-vivo and in-vitro. Age-related hypermethylation continued to change with passage, and linear modeling indicated that organoids age at an average rate of 0.46 months per week in culture. By contrast, hypomethylation occurred predominantly in non-aging-associated genomic regions such as non-promoter, non-CpG island regions (including transposable elements), and correlated neither with differentiation nor aging in-vivo. Thus, methylation changes in organoids reflect at least two different biological processes – aging, as measured by CpG island hypermethylation, and an unexplained stochastic hypomethylation defect. Treatment with the DNA methylation inhibitor decitabine lowered the methylation age of organoids from 22 months to 10 months, showing the potential of organoids to model extrinsic effects on age-related DNA hypermethylation.
Citation Format: Himani Vaidya, Gennaro Calendo, Anthomy Pompetti, Curt Balch, Kelsey Keith, Jozef Mazdo, Jaroslav Jelinek, Jean-Pierre Issa. Modeling age-related DNA methylation changes with intestinal organoids [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B027.
Abstract IA011: Heterochromatin deregulation during hematopoietic stem progenitor cell (HSPC) aging
Authors: Hong Tingting , Guo Lei , Guzman Anna , You James , Goodell Margaret , Zhou Yubin , Huang Yun 
Published: February 2025

Abstract
Aging is one of the major negative factors affecting normal hematopoiesis. Aged hematopoietic stem and progenitor cells (HSPCs) exhibit reduced self-renewal and increased myeloid bias during lineage specification, thereby sabotaging the immune system and increasing the risk of malignant transformation. Epigenetic dysregulation is a hallmark feature of aging and significantly contributes to age-related dysfunction across multiple biological systems. DNA methylation drift is commonly observed during aging, especially within late-replicated heterochromatin. DNA methylation and demethylation are maintained by DNMT and TET enzymes. Mutations in DNMT3A and TET2 are frequently observed in age-related clonal hematopoiesis (CH) and hematological malignancies. The impact of DNMT3A or TET2 loss-of-function on heterochromatin has recently gained recognition. Although heterochromatin is generally regarded as a gene-less region, it plays an important role in maintaining genome stability. Recently, we compared the impact of aging on WT and Tet2 knockout (KO) HSPCs. We observed that aging has less impact on Tet2KO HSPCs, which retain considerable clonal expansion capability during aging. However, WT HSPCs exhibited functional decline with age. At the molecular level, we identified the spatial relocation of heterochromatin from the nuclear periphery to the intranuclear region in aged WT HSPCs, but not in Tet2KO HSPCs. This relocation resulted in the upregulation of endogenous retroviruses (ERVs) and the promotion of innate immune responses in WT HSPCs, contributing to their functional decline during aging. This study adds a new dimension to understanding the functional interplay between DNA methylation and histone modifications in maintaining heterochromatin integrity and genome stability during stem cell aging.
Citation Format: Tingting Hong, Lei Guo, Anna Guzman, James You, Margaret Goodell, Yubin Zhou, Yun Huang. Heterochromatin deregulation during hematopoietic stem progenitor cell (HSPC) aging [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA011
Abstract IA014: Clinial implications of clonal hematopoiesis - and the role of Vitamin C
Authors: Grønbæk Kirsten 
Published: February 2025

Abstract
Dr Grønbæk will discuss the management of clonal hematopoiesis (CH) in clinical practice, focusing on how people with CH are identified. She will elaborate on the importance of identifying and following high-risk individuals/patients while sparing low risk individuals unnecessary worries. The role of DNA methylation changes in CH and low risk myeloid cancer will be discussed, including how preclinical studies have fostered the first clinical trials in CH. A special focus will be on the role of ascorbic acid (vitamin C) in CH and myeloid precursor conditions. Clinical- and correlative data from a randomized placebo controlled clinical trial: NCT03682029: A randomized, placebo-controlled, blinded, parallel-group clinical phase 2 study of oral vitamin C vs Placebo in CCUS/LR-MDS (EVITA) will be presented. The importance of enrolling these individuals/patients in clinical trials will be discussed including the optimal trials designs.
Citation Format: Kirsten Grønbæk. Clinial implications of clonal hematopoiesis - and the role of Vitamin C [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA014