bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation
Authors: van den Bosch Aletta M. R. , van der Poel Marlijn , Fransen Nina L. , Vincenten Maria C. J. , Bobeldijk Anneleen M. , Jongejan Aldo , Engelenburg Hendrik J. , Moerland Perry D. , Smolders Joost , Huitinga Inge , Hamann Jörg 
Published: February 2024

AbstractMicroglia nodules (HLA-DR+ cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology. Compared to microglia nodules in stroke, those in MS show enhanced expression of genes previously found upregulated in MS lesions. Furthermore, genes associated with lipid metabolism, presence of T and B cells, production of immunoglobulins and cytokines, activation of the complement cascade, and metabolic stress are upregulated in microglia nodules in MS. Compared to stroke, they more frequently phagocytose oxidized phospholipids and possess a more tubular mitochondrial network. Strikingly, in MS, some microglia nodules encapsulate partially demyelinated axons. Taken together, we propose that activation of microglia nodules in MS by cytokines and immunoglobulins, together with phagocytosis of oxidized phospholipids, may lead to a microglia phenotype prone to MS lesion formation.
A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation
Authors: Wang Qian , Yang Xingyue , Yuan Ruixin , Shen Ao , Wang Pushu , Li Haoting , Zhang Jun , Tian Chao , Jiang Zhujun , Li Wenzhe , Dong Suwei 
Published: February 2024

AbstractTargeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification of suitable degraders is essential for achieving effective protein degradation. Here, we present a non-covalent degrader construction strategy, based on a modular supramolecular co-assembly system consisting of two self-assembling peptide ligands that bind cell membrane receptors and the protein of interest simultaneously, resulting in targeted protein degradation. The developed lysosome-targeting co-assemblies (LYTACAs) can induce lysosomal degradation of extracellular protein IL-17A and membrane protein PD-L1 in several scavenger receptor A-expressing cell lines. The IL-17A-degrading co-assembly has been applied in an imiquimod-induced psoriasis mouse model, where it decreases IL-17A levels in the skin lesion and alleviates psoriasis-like inflammation. Extending to asialoglycoprotein receptor-related protein degradation, LYTACAs have demonstrated the versatility and potential in streamlining degraders for extracellular and membrane proteins.
Silencing Parkinson’s risk allele Rit2 sex-specifically compromises motor function and dopamine neuron viability
Authors: Kearney Patrick J. , Zhang Yuanxi , Liang Marianna , Tan Yanglan , Kahuno Elizabeth , Conklin Tucker L. , Fagan Rita R. , Pavchinskiy Rebecca G. , Shaffer Scott A. , Yue Zhenyu , Melikian Haley E. 
Published: February 2024

AbstractParkinson’s disease (PD) is the second most prevalent neurodegenerative disease and arises from dopamine (DA) neuron death selectively in the substantia nigra pars compacta (SNc). Rit2 is a reported PD risk allele, and recent single cell transcriptomic studies identified a major RIT2 cluster in PD DA neurons, potentially linking Rit2 expression loss to a PD patient cohort. However, it is still unknown whether Rit2 loss itself impacts DA neuron function and/or viability. Here we report that conditional Rit2 silencing in mouse DA neurons drove motor dysfunction that occurred earlier in males than females and was rescued at early stages by either inhibiting the DA transporter (DAT) or with L-DOPA treatment. Motor dysfunction was accompanied by decreased DA release, striatal DA content, phenotypic DAergic markers, DA neurons, and DAergic terminals, with increased pSer129-alpha synuclein and pSer935-LRRK2 expression. These results provide clear evidence that Rit2 loss is causal for SNc cell death and motor dysfunction, and reveal key sex-specific differences in the response to Rit2 loss.
Tandem catalysis enables chlorine-containing waste as chlorination reagents
Authors: Liu Mingyang , Wu Xinbang , Dyson Paul J. 
Published: February 2024

AbstractChlorinated compounds are ubiquitous. However, accumulation of chlorine-containing waste has a negative impact on human health and the environment due to the inapplicability of common disposal methods, such as landfill and incineration. Here we report a sustainable approach to valorize chlorine-containing hydrocarbon waste, including solids (chlorinated polymers) and liquids (chlorinated solvents), based on copper and palladium catalysts with a NaNO3 promoter. In the process, waste is oxidized to release the chlorine in the presence of N-directing arenes to afford valuable aryl chlorides, such as the FDA-approved drug vismodegib. The remaining hydrocarbon component is mineralized to afford CO, CO2 and H2O. Moreover, the CO and CO2 generated could be further utilized directly. Thus, chlorine-containing hydrocarbon waste, including mixed waste, can serve as chlorination reagents that neither generate hazardous by-products nor involve specialty chlorination reagents. This tandem catalytic approach represents a promising method for the viable management of a wide and diverse range of chlorine-containing hydrocarbon wastes.
Chromosome-level genome assembly and annotation of the Yunling cattle with PacBio and Hi-C sequencing data
Authors: Wei Zaichao , Zhang Lilian , Gao Lutao , Chen Jian , Peng Lin , Yang Linnan 
Published: February 2024

AbstractYunling cattle is a new breed of beef cattle bred in Yunnan Province, China. It is bred by crossing the Brahman, the Murray Grey and the Yunnan Yellow cattle. Yunling cattle can adapt to the tropical and subtropical climate environment, and has good reproductive ability and growth speed under high temperature and high humidity conditions, it also has strong resistance to internal and external parasites and with good beef performance. In this study, we generated a high-quality chromosome-level genome assembly of a male Yunling cattle using a combination of short reads sequencing, PacBio HiFi sequencing and Hi-C scaffolding technologies. The genome assembly(3.09 Gb) is anchored to 31 chromosomes(29 autosomes plus one X and Y), with a contig N50 of 35.97 Mb and a scaffold N50 of 112.01 Mb. It contains 1.62 Gb of repetitive sequences and 20,660 protein-coding genes. This first construction of the Yunling cattle genome provides a valuable genetic resource that will facilitate further study of the genetic diversity of bovine species and accelerate Yunling cattle breeding efforts.
Quantitative description of six fish species’ gut contents and prey abundances in the Baltic Sea (1968–1978)
Authors: Gauzens Benoit , Kalinkat Gregor , Antunes Ana Carolina , Boy Thomas , O’Gorman Eoin J. , Jacob Ute , Jochum Malte , Kortsch Susanne , Rosenbaum Benjamin , Figueiredo Ludmilla , Brose Ulrich 
Published: February 2024

AbstractThe dataset presents a compilation of stomach contents from six demersal fish species from two functional groups inhabiting the Baltic Sea. It includes detailed information on prey identities, body masses, and biomasses recovered from both the fish’s digestive systems and their surrounding environment. Environmental parameters, such as salinity and temperature levels, have been integrated to enrich this dataset. The juxtaposition of information on prey found in stomachs and in the environment provides an opportunity to quantify trophic interactions across different environmental contexts and investigate how fish foraging behaviour adapts to changes in their environment, such as an increase in temperature. The compilation of body mass and taxonomic information for all species allows approaching these new questions using either a taxonomic (based on species identity) or functional trait (based on body mass) approach.
Speech emotion recognition via graph-based representations
Authors: Pentari Anastasia , Kafentzis George , Tsiknakis Manolis 
Published: February 2024

AbstractSpeech emotion recognition (SER) has gained an increased interest during the last decades as part of enriched affective computing. As a consequence, a variety of engineering approaches have been developed addressing the challenge of the SER problem, exploiting different features, learning algorithms, and datasets. In this paper, we propose the application of the graph theory for classifying emotionally-colored speech signals. Graph theory provides tools for extracting statistical as well as structural information from any time series. We propose to use the mentioned information as a novel feature set. Furthermore, we suggest setting a unique feature-based identity for each emotion belonging to each speaker. The emotion classification is performed by a Random Forest classifier in a Leave-One-Speaker-Out Cross Validation (LOSO-CV) scheme. The proposed method is compared with two state-of-the-art approaches involving well known hand-crafted features as well as deep learning architectures operating on mel-spectrograms. Experimental results on three datasets, EMODB (German, acted) and AESDD (Greek, acted), and DEMoS (Italian, in-the-wild), reveal that our proposed method outperforms the comparative methods in these datasets. Specifically, we observe an average UAR increase of almost $$18\%$$

18
%

, $$8\%$$

8
%

and $$13\%$$

13
%

, respectively.
Development of renewable energy fed three-level hybrid active filter for EV charging station load using Jaya grey wolf optimization
Authors: Srilakshmi Koganti , Santosh D. Teja , Ramadevi Alapati , Balachandran Praveen Kumar , Reddy Ganesh Prasad , Palanivelu Aravindhababu , Colak Ilhami , Dhanamjayulu C. , Chinthaginjala Ravi Kumar , Khan Baseem 
Published: February 2024

AbstractThis work develops a hybrid active power filter (HAPF) in this article to operate in conjunction with the energy storage system (ESS), wind power generation system (WPGS), and solar energy system (SES). It employs three level shunt voltage source converters (VSC) connected to the DC-bus. Optimization of the gain values of the fractional-order proportional integral derivative controller (FOPIDC) and parameter values of the HAPF is achieved using the Jaya grey wolf hybrid algorithm (GWJA). The primary objectives of this study, aimed at enhancing power quality (PQ), include: (1) ensuring swift stabilization of DC link capacitor voltage (DCLCV); (2) reducing harmonics and improving power factor (PF); (3) maintaining satisfactory performance under different combinations of loads like EV charging load, non linear load and solar irradiation conditions. The proposed controller's performance is evaluated through three test scenarios featuring different load configurations and irradiation levels. Additionally, the HAPF is subjected to design using other optimization algorithms such as genetic algorithm (GA), particle swarm optimization (PSO), and ant colony optimization (ACO) to assess their respective contributions to PQ improvement.
Metabolomic associations of impaired awareness of hypoglycaemia in type 1 diabetes
Authors: Varkevisser R. D. M. , Cecil A. , Prehn C. , Mul D. , Aanstoot H. J. , Paterson A. D. , Wolffenbuttel B. H. R. , van der Klauw M. M. 
Published: February 2024

AbstractThis study investigates impaired awareness of hypoglycaemia (IAH), a complication of insulin therapy affecting 20–40% of individuals with type 1 diabetes. The exact pathophysiology is unclear, therefore we sought to identify metabolic signatures in IAH to elucidate potential pathophysiological pathways. Plasma samples from 578 individuals of the Dutch type 1 diabetes biomarker cohort, 67 with IAH and 108 without IAH (NAH) were analysed using the targeted metabolomics Biocrates AbsoluteIDQ p180 assay. Eleven metabolites were significantly associated with IAH. Genome-wide association studies of these 11 metabolites identified significant single nucleotide polymorphisms (SNPs) in C22:1-OH and phosphatidylcholine diacyl C36:6. After adjusting for the SNPs, 11 sphingomyelins and phosphatidylcholines were significantly higher in the IAH group in comparison to NAH. These metabolites are important components of the cell membrane and have been implicated to play a role in cell signalling in diabetes. These findings demonstrate the potential role of phosphatidylcholine and sphingomyelins in IAH.
Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer
Authors: Chen Dan-yang , Zhang Yang-yang , Nie Hai-hang , Wang Hai-zhou , Qiu Pei-shan , Wang Fan , Peng Ya-nan , Xu Fei , Zhao Qiu , Zhang Meng 
Published: February 2024

AbstractAs the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What’s more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.
Prolonged culturing of colonic epithelial organoids derived from healthy individuals and ulcerative colitis patients results in the decrease of LINE-1 methylation level
Authors: Inciuraite Ruta , Steponaitiene Ruta , Raudze Odeta , Kulokiene Ugne , Kiudelis Vytautas , Lukosevicius Rokas , Ugenskiene Rasa , Adamonis Kestutis , Kiudelis Gediminas , Jonaitis Laimas Virginijus , Kupcinskas Juozas , Skieceviciene Jurgita 
Published: February 2024

AbstractPatient-derived human intestinal organoids are becoming an indispensable tool for the research of digestive system in health and disease. However, very little is still known about the long-term culturing effect on global genomic methylation level in colonic epithelial organoids derived from healthy individuals as well as active and quiescent ulcerative colitis (UC) patients. In this study, we aimed to evaluate the epigenetic stability of these organoids by assessing the methylation level of LINE-1 during prolonged culturing. We found that LINE-1 region of both healthy control and UC patient colon tissues as well as corresponding epithelial organoids is highly methylated (exceeding 60%). We also showed that long-term culturing of colonic epithelial organoids generated from stem cells of healthy and diseased (both active and quiescent UC) individuals results in decrease of LINE-1 (up to 8%) methylation level, when compared to tissue of origin and short-term cultures. Moreover, we revealed that LINE-1 methylation level in sub-cultured organoids decreases at different pace depending on the patient diagnosis (healthy control, active or quiescent UC). Therefore, we propose LINE-1 as a potential and convenient biomarker for reliable assessment of global methylation status of patient-derived intestinal epithelial organoids in routine testing of ex vivo cultures.
UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120)
Authors: Margue Gaëlle , Ferrer Loïc , Etchepare Guillaume , Bigot Pierre , Bensalah Karim , Mejean Arnaud , Roupret Morgan , Doumerc Nicolas , Ingels Alexandre , Boissier Romain , Pignot Géraldine , Parier Bastien , Paparel Philippe , Waeckel Thibaut , Colin Thierry , Bernhard Jean-Christophe 
Published: February 2024

AbstractRenal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95% 0.77–0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95% 0.74–0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.
Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity
Authors: Wold Christian Winther , Christopoulos Panagiotis F. , Arias Maykel A. , Dzovor Deborah Elikplim , Øynebråten Inger , Corthay Alexandre , Inngjerdingen Kari Tvete 
Published: February 2024

AbstractFungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate β-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages.
Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice
Authors: Jiang Shan , Xie Weixin , Knapstein Paul Richard , Donat Antonia , Albertsen Lilly-Charlotte , Sevecke Jan , Erdmann Cordula , Appelt Jessika , Fuchs Melanie , Hildebrandt Alexander , Maleitzke Tazio , Frosch Karl-Heinz , Baranowsky Anke , Keller Johannes 
Published: February 2024

AbstractOsteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP−/− and CALCA−/− mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA−/− mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP−/− and WT mice. Osteophyte formation is reduced to the same extent in CALCA−/− and αCGRP−/− mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.
In-silico testing of new pharmacology for restoring inhibition and human cortical function in depression
Authors: Guet-McCreight Alexandre , Chameh Homeira Moradi , Mazza Frank , Prevot Thomas D. , Valiante Taufik A. , Sibille Etienne , Hay Etay 
Published: February 2024

AbstractReduced inhibition by somatostatin-expressing interneurons is associated with depression. Administration of positive allosteric modulators of α5 subunit-containing GABAA receptor (α5-PAM) that selectively target this lost inhibition exhibit antidepressant and pro-cognitive effects in rodent models of chronic stress. However, the functional effects of α5-PAM on the human brain in vivo are unknown, and currently cannot be assessed experimentally. We modeled the effects of α5-PAM on tonic inhibition as measured in human neurons, and tested in silico α5-PAM effects on detailed models of human cortical microcircuits in health and depression. We found that α5-PAM effectively recovered impaired cortical processing as quantified by stimulus detection metrics, and also recovered the power spectral density profile of the microcircuit EEG signals. We performed an α5-PAM dose-response and identified simulated EEG biomarker candidates. Our results serve to de-risk and facilitate α5-PAM translation and provide biomarkers in non-invasive brain signals for monitoring target engagement and drug efficacy.