bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-based Gene Expression Diagnosis of Mild and Moderate T-cell-mediated Rejection to Guide Therapy in Kidney Transplants
Authors: Kumar Dhiren , Raju Nihar , Tanriover Bekir , Azzouz Louiza , Moinuddin Irfan , Philogene Mary , Kamal Layla , McDougan Felecia , Massey Hugh Davis , Muthusamy Selvaraj , Lee Inkoo , Halloran Philip , Gupta Gaurav 
Published: December 2024

Background.
Mild histologic lesions of tubulo-interstitial inflammation could represent a “response-to-wounding” rather than allorecognition. Tissue gene expression may complement histopathology for T-cell-mediated rejection (TCMR) diagnostics.

Methods.
We report on the incorporation of tissue gene expression testing using a Molecular Microscope Diagnostic System into the management of kidney transplant biopsies with suspected TCMR. Patients (N = 209) were divided into 3 groups based upon diagnosis and TCMR therapy (with high-dose steroids and/or anti-thymocyte globulin): Group 1: Untreated histologic TCMR with molecular quiescence (H+M–); Group 2: Treated histologic and molecular TCMR (H+M+); and Group 3: Controls, with no histologic or molecular (H–M–) rejection.

Results.
At biopsy, estimated glomerular filtration rate was worse (P = 0.006) in H+M+ (N = 35; 33 ± 22 mL/min/1.73 m2) and H+M– (N = 30; 40 ± 18 mL/min/1.73 m2) groups; compared with H–M– (N = 144; 47 ± 24 mL/min/1.73 m2) group. In H+M– biopsies, mean molecular acute kidney injury scores (0.33 versus 0.10; P = 0.03) were higher than in H–M–; while molecular TCMR was lower compared with H+M+ (0.04 versus 0.54; P < 0.001). At 12 m postbiopsy estimated glomerular filtration rate remained low (P < 0.001) in H+M+ (38 ± 22 mL/min/1.73 m2) but improved in untreated H+M– (44 ± 22 mL/min/1.73 m2) and H–M– (50 ± 23 mL/min/1.73 m2) groups. At a mean follow-up of 2.1 ± 1.2 y post-index biopsy, death-censored graft survival was lower in H+M+ (74%) than in H+M– (90%) and H–M– (92%; P = 0.001). H+M+ cases had numerically higher rejection on follow-up biopsy (20%) than H+M– (7%) (P = 0.12) and de novo donor-specific antibody formation (H+M+ 24%; H+M– 10%; P = 0.13).

Conclusions.
In this large single-center study, biopsies with untreated histological TCMR and molecular quiescence had comparable clinical outcomes to cases with no rejection, whereas those with histologic and tissue gene expression confirmed TCMR had inferior outcomes.
Divergent effects of cytomegalovirus and rheumatoid arthritis on senescent CD4+T cells
Authors: Williams Lea , Saber Ali O. , Xu Ruozhang , Jung Hannah , Awad Silina , Shahane Anupama , Baker Joshua F. , Su Laura F. 
Published: December 2024

AbstractCD4+T cell senescence has been linked to repeated antigen stimulation. However, how different types of chronic antigenic exposures impact T cell differentiation and function remains incompletely understood. Using rheumatoid arthritis (RA) and cytomegalovirus (CMV) as models for persistent stimulation in autoimmunity and chronic viral infection, we performed high-dimensional mass cytometry analyses to examine their effects on CD4+T cell differentiation. We found that CMV seropositive adults have a significant population of highly differentiated CD27-CD28-CD4+T cells that exhibited common features of senescence, including CD57 and cytotoxic granule expression. In contrast, CD27-CD28-CD4+T cells were rare in RA patients and Epstein-Barr virus (EBV) or Herpes simplex virus (HSV) seropositive individuals. The few that were present exhibited a predominantly non-cytotoxic profile, with higher expression of TCF1, CD127, and Ki67. Among CMV seropositive individuals, RA was associated with reduced degranulation of cytotoxic granules and lower cytokine production by senescent CD4+T cells. We did not find an association with age, sex, clinical characteristics, or medication usage by univariate linear regression analyses. However,in vitrotofacitinib treatment reduced T cell functional activity, suggesting contributions from both the disease and RA treatment. These data uncovered distinct influences from CMV and RA, and their combined impact on senescent CD4+T cell differentiation and function.
Harnessing Environmental DNA (eDNA) to Explore Frugivorous Interactions: A Case Study in Papaya (Carica papaya) and Pineapple (Ananas comosus)
Authors: Banerjee Pritam , Maity Jyoti Prakash , Chatterjee Nalonda , Weber Sven , Dey Gobinda , Sharma Raju Kumar , Chen Chien-Yen 
Published: December 2024

AbstractPlant-animal interactions (PAIs) are critical in ecosystem function, mediating energy flow and species interactions. Traditional methods of tracking PAIs, such as morphological identification and camera trapping, are limited in speed and scalability, posing challenges for comprehensive biodiversity monitoring. Recently, environmental DNA (eDNA) metabarcoding has emerged as a promising technique for detecting species interactions non-destructively. This pilot study explores the application of eDNA metabarcoding to investigate interactions involving partially consumed and intact fruits ofCarica papayaandAnanas comosus. eDNA metabarcoding were performed from of 36 partially consumed and 6 intact fruit samples. Metabarcoding of mitochondrial COI gene fragments revealed a diverse range of taxa, with Arthropoda, particularly insects, being the most abundant. Results indicated significant differences in taxonomic composition between pineapple and papaya samples, where both the fruit hold some unique as well as shared taxa. Furthermore, the diversity also differed between consumed and intact fruits, suggesting that partially consumed fruits serve as rich eDNA sources, capturing interactions with various frugivores and decomposers. Signal from various organisms detected through eDNA metabarcoding from consumed and damaged fruits allowed us to capture a wide array of taxa, revealing insights into species composition and ecological relationships. The unique ASVs associated with each fruit type suggest that certain taxa may showing preferences based on fruit characteristics such as sugar content, texture, or chemical profile. Present work highlighted the importance of eDNA based methods in unraveling the taxonomic composition of fruit-associated plant-animal interactions. This method needs limited taxonomic expertise, less labors, fast and effective, which can be implemented in monitoring ecological and economical species interactions.
Extrachromosomal DNA-mediated glutamine synthetase 2 (GS2) amplification enables glufosinate resistance inAmaranthus palmeri
Authors: Noguera Matheus M , Albert Patrice S , Saski Christopher A , Birchler James A , Porri Aimone , Meiners Ingo , Lerchl Jens , Roma-Burgos Nilda 
Published: December 2024

AbstractBackgroundPalmer amaranth achieves resistance to glufosinate by overproducing the chloroplastic glutamine synthetase (GS2) protein, a result of the amplification and overexpression of its nuclear coding gene. This study examined how amplifiedGS2copies are inherited, identified their physical location in the cell, and investigated the mechanism ofGS2amplification.ResultsSegregation analysis revealed that inheritance of amplifiedGS2copies deviates from classical Mendelian patterns, with poor correlation between plant level resistance andGS2amplification. Fluorescencein situhybridization revealed chromosomal insertions ofGS2and potential extrachromosomal circular DNA (eccDNA), and variability inGS2amplification both among individual plants and within cells (not all cells in plants with highGS2copy number showed GS2 amplification). The unpredictable inheritance patterns and distribution ofGS2copies across multiple chromosomes suggest a role for eccDNA inGS2amplification. This was confirmed through eccDNA sequencing, which also identified multiple isoforms ofGS2.ConclusionThis is the second documented case of herbicide resistance conferred by eccDNA-mediated target-site gene amplification in Palmer amaranth.
Natural monoclonal autoantibodies against HERV-K102 Envelope-TM from SLE patients selectively eliminate autoreactive immune cells and cancer cells
Authors: Gong Qinyuan , Li Mengyuan , Zheng Shuwen , Wu Zhaoxing , Wang Ping , Zhang Xuzhao , Liang Yun , Qian Wenbin , Xu Rongzhen 
Published: December 2024

AbstractIn sharp contrast to immune dysfunction in cancer, autoimmune diseases such as systemic lupus erythematosus (SLE) exhibit excessive immune reactions characterized by high titers of autoantibodies to HERV-K102-envelope (HERV-K102-Env) neoantigens, which are frequently found in cancer patients but seldom elicit a strong immune response. Here we aim to address whether anti-HERV-K102-Env autoantibodies in SLE can effectively eliminate autoreactive immune cells and cancer cells expressing HERV-K102-Env neoantigens. We established world-first fully human autoantibody phage display library with 3.67x108cfu using peripheral blood mononuclear cells (PBMCs) from SLE patients. Through high-throughput screening, we identified nineteen monoclonal autoantibodies (mAbs) targeting the conserved HERV-K102 Env-TM subunit. The EC50 values of these autoantibodies binding to the HERV-K102 Env-TM subunit ranged from 0.002436 μg/ml to 1.798 μg/ml. Remarkably, eleven of these mAbs not only recognized the HERV-K102 Env-TM glycoprotein on the cell surface but also effectively eliminated autoreactive B, T, and natural killer (NK) cells in SLE, as well as cancer cells. Our findings provide a conceptually new immunotherapy target HERV-K102 Env-TM subunit and open the era of using natural human autoantibodies to treat autoimmune disease and cancers.Several of these monoclonal autoantibodies show promise as potential diagnostic and therapeutic agents, paving the way for innovative approaches to treating SLE and various malignancies.
Enabling Hydrogel Coating on Silicone Breast Implants with Poly(Vinyl Acetate) Primer Layer
Authors: Stanger Katrin , Bajrami Dardan , Wahl Peter , Moriarty Fintan , Gautier Emanuel , Dommann Alex , Wei Kongchang 
Published: December 2024

AbstractImplant-associated infection is a major cause for breast implant re-operation. A practical method to reduce this risk is yet to be established. Hydrogel coating represents one promising approach. However, the adhesion of the hydrogel layer onto the silicone implant surface presents a significant challenge due to the intrinsic hydrophobicity of silicone surfaces. In this study, we described a surface-priming strategy involving poly(vinyl acetate) (PVAc) polymers to facilitate hydrogel adhesion to silicone implant surfaces. Miniature silicone implants with identical surface properties to clinical implants were custom-made for this study. We demonstrated that a PVAc primer layer can easily be deposited on the implant surface via a dip-coating procedure. The wettability of the implant surface was increased by this primer layer, as confirmed by contact angle measurements. The improved wettability allowed the application of a model hydrogel precursor solution (alginate) on the primed implant surface. The effectiveness of such a priming strategy in facilitating hydrogel coating was validated by testing two commercially available hydrogels on the silicone implant surface. Specifically, DAC (Defensive Antibacterial Coating) and Coseal hydrogels, representing paintable and sprayable hydrogels respectively, were successfully coated on the primed surface, as confirmed by ATR-FTIR analysis. Our surface priming strategy, which avoids surface treatments like chemical reactions and plasma irradiation that are impractical for clinical use, opens up new opportunities for exploring intraoperative hydrogel applications on silicone implants.
Blood-borne immune cells carry low biomass DNA remnants of microbes in patients with colorectal cancer or inflammatory bowel disease
Authors: Morsy Y. , Walberg Å. , Wawrzyniak P. , Hubeli B. , Truscello L. , Mamie C. , Niechcial A. , Gueguen E. , Manzini R. , Gottier C. , Lang S. , Scharl S. , Blümel S. , Biedermann L. , Rogler G. , Turina M. , Ramser M. , Petrowsky H. , Arnold I. C. , Zeissig S. , Zamboni N. , Egli A. , Niess J. H. , Hruz P. , Knuth A. , Fritsch R. , Manz M. G. , Wawrzyniak M. , Scharl M. 
Published: December 2024

AbstractThe involvement of the human intestinal microbiome in the regulation of immune cell homeostasis, as well as in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC), are well-established1–4. Bacteria interact with immune cells at the sites of intestinal inflammation, but also in the CRC tumor microenvironment1–6. Indeed, bacterial remnants have recently been detected in human intestinal tissue in patients with IBD, at primary tumor sites and in the metastases of patients with CRC, and in whole blood3,7,8. A defective intestinal epithelial barrier is thought to promote bacterial remnant translocation and disease progression6. However, it is unknown, how bacterial remnants translocate from the intestine to sites of metastasis or into the circulation. We hypothesized that bacterial remnants translocate within peripheral blood immune cells into the circulation. Here, we thus explored the composition of the detectable microbiome in peripheral blood mononuclear cells (PBMCs) of patients with CRC or IBD compared to healthy controls. The PBMC microbiome profiles partially align with the tumor- and metastasis-derived or intestinal tissue-derived microbiome signatures obtained from the same patients with CRC or IBD, respectively. Our metagenomics data, supported by 16S-rRNA-FISH-Flow, imaging flow cytometry and species-specific qPCR, reveal the presence of translocated bacterial genetic sequences in the patients with CRC and IBD, likely due to an intestinal barrier defect. Pathway and serum metabolomics analysis connected to the metabolic potential of the PBMC-derived microbiome sequences support the onset of microbial translocation in such patients. Thus, our data suggest that in patients with intestinal barrier leakage, such as those with CRC or IBD, there is the potential for the translocation of bacterial remnants into the circulation via peripheral immune cells.
Investigating BPDE-induced embryonic toxicity employing hiPSC-based models
Authors: Meira de Amorim Vanessa Cristina , Szepanowski Leon , Lofrano Alessia , Loerch Christiane , Wruck Wasco , Graffmann Nina , Adjaye James 
Published: December 2024

AbstractBenzo[a]pyrene diol epoxide (BPDE) is a metabolite of the environmental contaminant Benzo[a]pyrene- a byproduct of incomplete combustion of organic matter. BPDE reacts with DNA to form BPDE-DNA bulky adducts which if not removed can lead to mutations due to DNA base-pair substitutions. While the effects of BPDE on somatic cells are fairly well described, its effects on early human development are currently unknown. In this study, we investigated for the first time the effect of BPDE on human induced pluripotent stem cells (hiPSCs) and their differentiated neuroprogenitor cells (NPCs) as a model for early embryonic development. Furthermore, we compared hiPSCs and NPCs derived from cells of patients suffering from Nijmegen Breakage Syndrome (NBS), which is a chromosomal instability disorder characterized by defective DNA repair and increased risk of malignancies. Transcriptome analysis, coupled with protein content analysis employing immunostaining and Western blots, revealed that hiPSCs are more sensitive to BPDE exposure when compared to NPCs with an enhanced expression of several genes associated with p53-mediated DNA damage response, including DNA repair by lesion bypass, cell cycle checkpoints and extrinsic apoptosis. We also identified that cells from NBS patients showed less apoptotic response and a distinct p53 response than their healthy counterparts. This iPSC-based study enhances our meagre knowledge of the effects of BPDE on early human development in both healthy individuals and NBS patients. Furthermore, our model conforms with the 3Rs principle.
Astrocytic Signatures in Neuronal Activity: A Machine Learning-Based Identification Approach
Authors: Pirola João Pedro , DeForest Paige , Protachevicz Paulo R , Fontenas Laura , Ferreira Ricardo F , Pena Rodrigo FO 
Published: December 2024

AbstractThis study investigates the expanding role of astrocytes, the predominant glial cells, in brain function, focusing on whether and how their presence influences neuronal network activity. We focus on particular network activities identified as synchronous and asynchronous. Using computational modeling to generate synthetic data, we examine these network states and find that astrocytes significantly affect synaptic communication, mainly in synchronous states. We use different methods of extracting data from a network and compare which is best for identifying glial cells, with mean firing rate emerging with higher accuracy. To reach the aforementioned conclusions, we applied various machine learning techniques, including Decision Trees, Random Forests, Bagging, Gradient Boosting, and Feedforward Neural Networks, the latter outperforming other models. Our findings reveal that glial cells play a crucial role in modulating synaptic activity, especially in synchronous networks, highlighting potential avenues for their detection with machine learning models through experimental accessible measures.
Classifying Domains, Benchmarking GPT-4, A Portuguese Dataset for Medical AI Q&A
Authors: Matsuoka Felipe Akio , Onaga Henrique Nunes 
Published: December 2024

ABSTRACTArtificial Intelligence (AI), particularly large language models (LLMs), has demonstrated remarkable capabilities in addressing complex tasks, including professional-level medical question answering. While standardized benchmarks like the USMLE have been widely used for evaluating LLM performance in English, there is a significant gap in evaluating these models in other languages, such as Portuguese. To address this, we present a curated dataset derived from the Teste de Progresso (TP), a widely adopted Brazilian progress test used to assess medical knowledge across six key domains: Basic Sciences, Internal Medicine, Surgery, Obstetrics and Gynecology, Public Health, and Pediatrics. The dataset consists of 720 multiple-choice questions spanning five years (2019–2023). We demonstrate two primary applications of this dataset. First, we benchmark the performance of GPT-4, which achieved an overall accuracy of 90% across the six medical domains, with the highest performance in Internal Medicine (10%) and the lowest in Public Health (80%). Second, we develop a classification model based on BERTimbau, achieving an overall accuracy of 94% in categorizing questions into their respective medical domains. Our results highlight the utility of the dataset for both benchmarking AI models and automating medical question classification. This work emphasizes the importance of creating domain-specific datasets in underrepresented languages, like Portuguese, to advance AI-driven medical applications, ensure equitable access to AI technologies, and address linguistic and cultural gaps in healthcare education.
Silent reservoirs are shaping disease emergence: the case of Usutu virus in the Netherlands
Authors: de Wit M.M. , Beaunée G. , Dellar M. , Münger E. , Krol L. , Atama N. , van Irsel J. , van der Jeugd H. , Koopmans M. , de Jong M.C.M. , Sikkema R. S. , ten Bosch Q. 
Published: December 2024

AbstractDisentangling contributions of different hosts to disease emergence and spread is highly complex, but critical for improving predictions, surveillance, and response. This is particularly challenging in wildlife, with pathogens often infecting multiple species and data collection being difficult. Using the emergence of Usutu virus (USUV) in the Netherlands as a case study, we demonstrate the use of an Approximate Bayesian Computation framework on diverse data sources to uncover hidden drivers of spatio-temporal wildlife disease emergence. We calibrated single- and multi-host mechanistic transmission models to five types of wildlife surveillance and research data, describing molecular and serological evidence of USUV in wild birds. Although Eurasian blackbirds, the primary sentinel species, were the most severely affected species, our models indicated that USUV could not persist in blackbirds alone. Our data-model framework provided statistical support for additional bird species to have contributed to transmission. This population of bird species is characterised by limited infection mortality, a longer lifespan, and likely further dispersal than blackbirds. Immunity in this reservoir population appears to have protected blackbirds from further USUV-related population decline. Continued surveillance could help identify these reservoir species. Our results underscore the importance of considering multiple host populations to understand outbreak dynamics. Neglecting the multi-host context of disease transmission can impact the reliability of future predictions and the projected impact of intervention strategies.Significance statementUnderstanding which species contribute to disease transmission is critical for improving predictions, surveillance, and response. However, disentangling these contributions is difficult, especially for wildlife diseases where pathogens often infect multiple species and data collection is notoriously difficult. Using Usutu virus (USUV) in the Netherlands as an example, we show how a computational framework can integrate diverse wildlife data sources to uncover hidden contributors to transmission. Our findings show that blackbirds, the most severely affected species, cannot sustain USUV transmission alone. Additional bird species, characterised by lower infection mortality and longer lifespans, are important for transmission and may protect more vulnerable species. This work emphasizes that studying transmission in a multi-host context is crucial for accurate outbreak predictions and effective interventions.
A comprehensive benchmark for multiple highly efficient base editors with broad targeting scope
Authors: Wang Xiaofeng , Cheng Xiaolong , Li Zexu , Ma Shixin , Zhang Han , Chen Zhisong , Yao Yingjia , Li Zihan , Zhong Chunge , Li You , Zhang Yunhan , Menon Vipin , Chao Lumen , Li Wei , Fei Teng 
Published: December 2024

AbstractAs the toolbox of base editors (BEs) expands, selecting appropriate BE and guide RNA (gRNA) to achieve optimal editing efficiency and outcome for a given target becomes challenging. Here, we construct a set of 10 adenine and cytosine BEs with high activity and broad targeting scope, and comprehensively evaluate their editing profiles and properties head-to-head with 34,040 BE-gRNA-target combinations using genomically integrated long targets and tiling gRNA strategies. Interestingly, we observe widespread non-canonical protospacer adjacent motifs (PAMs) for these BEs. Using this large-scale benchmark data, we build a deep learning model, named BEEP (BaseEditingEfficiencyPredictor), for predicting the editing efficiency and outcome of these BEs. Guided by BEEP, we experimentally test and validate the installment of 3,558 disease-associated single nucleotide variants (SNVs) via BEs, including 20.1% of target sites that would be generally considered as “uneditable”, due to the lack of canonical PAMs. We further predict candidate BE-gRNA-target combinations for modeling 1,752,651 ClinVar SNVs. We also identify several cancer-associated SNVs that drive the resistance to BRAF inhibitors in melanoma. These efforts benchmark the performance and illuminate the capabilities of multiple highly useful BEs for interrogating functional SNVs. A practical webserver (http://beep.weililab.org/) is freely accessible to guide the selection of optimal BEs and gRNAs for a given target.