bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder
Authors: Sala-Gaston Joan , Pérez-Villegas Eva M. , Armengol José A. , Rawlins Lettie E. , Baple Emma L. , Crosby Andrew H. , Ventura Francesc , Rosa Jose Luis 
Published: April 2024

AbstractSequence variants in the HERC2 gene are associated with a significant reduction in HERC2 protein levels and cause a neurodevelopmental disorder known as the HERC2-related disorder, which shares clinical features with Angelman syndrome, including global developmental delay, intellectual disability, autism, and movement disorders. Remarkably, the HERC2 gene is commonly deleted in individuals with Angelman syndrome, suggesting a potential contribution of HERC2 to the pathophysiology of this disease. Given the known critical role of autophagy in brain development and its implication in neurodevelopmental diseases, we undertook different experimental approaches to monitor autophagy in fibroblasts derived from individuals affected by the HERC2-related disorder. Our findings reveal alterations in the levels of the autophagy-related protein LC3. Furthermore, experiments with lysosomal inhibitors provide confirmation of an upregulation of the autophagy pathway in these patient-derived cells. Mechanistically, we corroborate an interaction between HERC2 and the deubiquitylating enzyme USP20; and demonstrate that HERC2 deficiency leads to increased USP20 protein levels. Notably, USP20 upregulation correlates with enhanced stability of the autophagy initiating kinase ULK1, highlighting the role of HERC2 as an autophagy regulator factor through the USP20-ULK1 axis. Moreover, we show that p38 acts as a modulator of this pathway, since p38 activation disrupts HERC2-USP20 interaction, leading to increased USP20 and LC3-II protein levels. Together, these findings uncover a previously unknown role for HERC2 in autophagy regulation and provide insights into the pathomolecular mechanisms underlying the HERC2-related disorder and Angelman syndrome.
RedOx regulation of LRRK2 kinase activity by active site cysteines
Authors: Trilling Chiara R. , Weng Jui-Hung , Sharma Pallavi Kaila , Nolte Viktoria , Wu Jian , Ma Wen , Boassa Daniela , Taylor Susan S. , Herberg Friedrich W. 
Published: April 2024

AbstractMutations of the human leucine-rich repeat kinase 2 (LRRK2) have been associated with both, idiopathic and familial Parkinson’s disease (PD). Most of these pathogenic mutations are located in the kinase domain (KD) or GTPase domain of LRRK2. In this study we describe a mechanism in which protein kinase activity can be modulated by reversible oxidation or reduction, involving a unique pair of adjacent cysteines, the “CC” motif. Among all human protein kinases, only LRRK2 contains this “CC” motif (C2024 and C2025) in the Activation Segment (AS) of the kinase domain. In an approach combining site-directed mutagenesis, biochemical analyses, cell-based assays, and Gaussian accelerated Molecular Dynamics (GaMD) simulations we could attribute a role for each of those cysteines. We employed reducing and oxidizing agents with potential clinical relevance to investigate effects on kinase activity and microtubule docking. We find that each cysteine gives a distinct contribution: the first cysteine, C2024, is essential for LRRK2 protein kinase activity, while the adjacent cysteine, C2025, contributes significantly to redox sensitivity. Implementing thiolates (R-S-) in GaMD simulations allowed us to analyse how each of the cysteines in the “CC” motif interacts with its surrounding residues depending on its oxidation state. From our studies we conclude that oxidizing agents can downregulate kinase activity of hyperactive LRRK2 PD mutations and may provide promising tools for therapeutic strategies.
A two-way street – cellular metabolism and myofibroblast contraction
Authors: Noom Anne , Sawitzki Birgit , Knaus Petra , Duda Georg N. 
Published: April 2024

AbstractTissue fibrosis is characterised by the high-energy consumption associated with myofibroblast contraction. Although myofibroblast contraction relies on ATP production, the role of cellular metabolism in myofibroblast contraction has not yet been elucidated. Studies have so far only focused on myofibroblast contraction regulators, such as integrin receptors, TGF-β and their shared transcription factor YAP/TAZ, in a fibroblast-myofibroblast transition setting. Additionally, the influence of the regulators on metabolism and vice versa have been described in this context. However, this has so far not yet been connected to myofibroblast contraction. This review focuses on the known and unknown of how cellular metabolism influences the processes leading to myofibroblast contraction and vice versa. We elucidate the signalling cascades responsible for myofibroblast contraction by looking at FMT regulators, mechanical cues, biochemical signalling, ECM properties and how they can influence and be influenced by cellular metabolism. By reviewing the existing knowledge on the link between cellular metabolism and the regulation of myofibroblast contraction, we aim to pinpoint gaps of knowledge and eventually help identify potential research targets to identify strategies that would allow switching tissue fibrosis towards tissue regeneration.
Registered multi-device/staining histology image dataset for domain-agnostic machine learning models
Authors: Ochi Mieko , Komura Daisuke , Onoyama Takumi , Shinbo Koki , Endo Haruya , Odaka Hiroto , Kakiuchi Miwako , Katoh Hiroto , Ushiku Tetsuo , Ishikawa Shumpei 
Published: April 2024

AbstractVariations in color and texture of histopathology images are caused by differences in staining conditions and imaging devices between hospitals. These biases decrease the robustness of machine learning models exposed to out-of-domain data. To address this issue, we introduce a comprehensive histopathology image dataset named PathoLogy Images of Scanners and Mobile phones (PLISM). The dataset consisted of 46 human tissue types stained using 13 hematoxylin and eosin conditions and captured using 13 imaging devices. Precisely aligned image patches from different domains allowed for an accurate evaluation of color and texture properties in each domain. Variation in PLISM was assessed and found to be significantly diverse across various domains, particularly between whole-slide images and smartphones. Furthermore, we assessed the improvement in domain shift using a convolutional neural network pre-trained on PLISM. PLISM is a valuable resource that facilitates the precise evaluation of domain shifts in digital pathology and makes significant contributions towards the development of robust machine learning models that can effectively address challenges of domain shift in histological image analysis.
Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis
Authors: Nascimento-Carvalho Bruno , da Silva Bruno Durante , da Silva Maikon Barbosa , Dos-Santos Adriano , Ribeiro Thayna Fabiana , da Silva Dias Danielle , de Souza Leandro Eziquiel , Dutra Marina Rascio Henriques , Catanozi Sergio , Caldini Elia G. , De Angelis Kátia , Scapini Katia Bilhar , Sanches Iris Callado , Irigoyen Maria Claudia 
Published: April 2024

AbstractCardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.
ANN: adversarial news net for robust fake news classification
Authors: Maham Shiza , Tariq Abdullah , Khan Muhammad Usman Ghani , Alamri Faten S. , Rehman Amjad , Saba Tanzila 
Published: April 2024

AbstractWith easy access to social media platforms, spreading fake news has become a growing concern today. Classifying fake news is essential, as it can help prevent its negative impact on individuals and society. In this regard, an end-to-end framework for fake news detection is developed by utilizing the power of adversarial training to make the model more robust and resilient. The framework is named "ANN: Adversarial News Net," emoticons have been extracted from the datasets to understand their meanings concerning fake news. This information is then fed into the model, which helps to improve its performance in classifying fake news. The performance of the ANN framework is evaluated using four publicly available datasets, and it is found to outperform baseline methods and previous studies after adversarial training. Experiments show that Adversarial Training improved the performance by 2.1% over the Random Forest baseline and 2.4% over the BERT baseline method in terms of accuracy. The proposed framework can be used to detect fake news in real-time, thereby mitigating its harmful effects on society.
HD-tDCS mitigates the executive vigilance decrement only under high cognitive demands
Authors: Hemmerich Klara , Lupiáñez Juan , Martín-Arévalo Elisa 
Published: April 2024

AbstractMaintaining vigilance is essential for many everyday tasks, but over time, our ability to sustain it inevitably decreases, potentially entailing severe consequences. High-definition transcranial direct current stimulation (HD-tDCS) has proven to be useful for studying and improving vigilance. This study explores if/how cognitive load affects the mitigatory effects of HD-tDCS on the vigilance decrement. Participants (N = 120) completed a modified ANTI-Vea task (single or dual load) while receiving either sham or anodal HD-tDCS over the right posterior parietal cortex (rPPC). This data was compared with data from prior studies (N = 120), where participants completed the standard ANTI-Vea task (triple load task), combined with the same HD-tDCS protocol. Against our hypotheses, both the single and dual load conditions showed a significant executive vigilance (EV) decrement, which was not affected by the application of rPPC HD-tDCS. On the contrary, the most cognitively demanding task (triple task) showed the greatest EV decrement; importantly, it was also with the triple task that a significant mitigatory effect of the HD-tDCS intervention was observed. The present study contributes to a more nuanced understanding of the specific effects of HD-tDCS on the vigilance decrement considering cognitive demands. This can ultimately contribute to reconciling heterogeneous effects observed in past research and fine-tuning its future clinical application.
Experience shapes non-linearities between team behavioral interdependence, team collaboration, and performance in massively multiplayer online games
Authors: Carrasco-Farré Carlos , Hakobjanyan Nancy 
Published: April 2024

AbstractThis paper examines quantitative predictors of team performance in Massively Multiplayer Online Games (MMOGs) based on team management literature. Analyzing data from more than 140,000 squad-mode matches involving over 500,000 players, we replicate and extend existing research by confirming a curvilinear association between behavioral interdependence and team performance and introduce the moderating effect of experience. For less experienced teams, behavioral interdependence follows an inverted U-shaped pattern showing that excessive collaboration may be counterproductive. However, this is not the case for experienced teams, where the relationship is fairly linear. Additionally, we observe that riskier teams tend to perform worse. Moreover, our research also highlights the potential of e-sports data in advancing behavioral science and management research. The digital nature of e-sports datasets, characterized by size and granularity, mitigates concerns related to reproducibility, replicability, and generalizability in social science research, offering a cost-effective platform for scholars with diverse backgrounds.
SU-101 for the removal of pharmaceutical active compounds by the combination of adsorption/photocatalytic processes
Authors: Chacón-García Antonio J. , Rojas Sara , Grape Erik Svensson , Salles Fabrice , Willhammar Tom , Inge A. Ken , Pérez Yolanda , Horcajada Patricia 
Published: April 2024

AbstractPharmaceutical active compounds (PhACs) are some of the most recalcitrant water pollutants causing undesired environmental and human effects. In absence of adapted decontamination technologies, there is an urgent need to develop efficient and sustainable alternatives for water remediation. Metal–organic frameworks (MOFs) have recently emerged as promising candidates for adsorbing contaminants as well as providing photoactive sites, as they possess exceptional porosity and chemical versatility. To date, the reported studies using MOFs in water remediation have been mainly focused on the removal of a single type of PhACs and rarely on the combined elimination of PhACs mixtures. Herein, the eco-friendly bismuth-based MOF, SU-101, has been originally proposed as an efficient adsorbent-photocatalyst for the elimination of a mixture of three challenging persistent PhACs, frequently detected in wastewater and surface water in ng L−1 to mg·L−1 concentrations: the antibiotic sulfamethazine (SMT), the anti-inflammatory diclofenac (DCF), and the antihypertensive atenolol (At). Adsorption experiments of the mixture revealed that SU-101 exhibited a great adsorption capacity towards At, resulting in an almost complete removal (94.1 ± 0.8% for combined adsorption) in only 5 h. Also, SU-101 demonstrated a remarkable photocatalytic activity under visible light to simultaneously degrade DCF and SMT (99.6 ± 0.4% and 89.2 ± 1.4%, respectively). In addition, MOF-contaminant interactions, the photocatalytic mechanism and degradation pathways were investigated, also assessing the toxicity of the resulting degradation products. Even further, recycling and regeneration studies were performed, demonstrating its efficient reuse for 4 consecutive cycles without further treatment, and its subsequent successful regeneration by simply washing the material with a NaCl solution.
Regional reef fish assemblage maps provide baseline biogeography for tropicalization monitoring
Authors: Walker Brian K. , Fisco Becker Dana , Williams Gareth J. , Kilfoyle Audie K. , Smith Steven G. , Kozachuk Allie 
Published: April 2024

AbstractThe Anthropocene rise in global temperatures is facilitating the expansion of tropical species into historically non-native subtropical locales, including coral reef fish. This redistribution of species, known as tropicalization, has serious consequences for economic development, livelihoods, food security, human health, and culture. Measuring the tropicalization of subtropical reef fish assemblages is difficult due to expansive species ranges, temporal distribution shifts with the movement of isotherms, and many dynamic density-dependent factors affecting occurrence and density. Therefore, in locales where tropical and subtropical species co-occur, detecting tropicalization changes relies on regional analyses of the relative densities and occurrence of species. This study provides a baseline for monitoring reef fish tropicalization by utilizing extensive monitoring data from a pivotal location in southeast Florida along a known transition between tropical and subtropical ecotones to define regional reef fish assemblages and use benthic habitat maps to spatially represent their zoogeography. Assemblages varied significantly by ecoregion, habitat depth, habitat type, and topographic relief. Generally, the southern assemblages had higher occurrences and densities of tropical species, whereas the northern assemblages had a higher occurrence and density of subtropical species. A total of 108 species were exclusive to regions south of the Bahamas Fracture Zone (BFZ) (South Palm Beach, Deerfield, Broward-Miami) and 35 were exclusive to the north (North Palm Beach, Martin), supporting the BFZ as a pivotal location that affects the coastal biogeographic extent of tropical marine species in eastern North America. Future tropicalization of reef fish assemblages are expected to be evident in temporal deviance of percent occurrence and/or relative species densities between baseline assemblages, where the poleward expansion of tropical species is expected to show the homogenization of assemblage regions as adjacent regions become more similar or the regional boundaries expand poleward. Ecoregions, habitat depth, habitat type, and relief should be incorporated into the stratification and analyses of reef fish surveys to statistically determine assemblage differences across the seascape, including those from tropicalization.
Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice
Authors: Yamagishi-Kimura Reiko , Honjo Megumi , Aihara Makoto 
Published: April 2024

AbstractRipasudil–brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited reduced EVP until 60 min after instillation. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes, whereas brimonidine did not. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, and the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow; K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.
Human health risk of nitrate in groundwater of Tehran–Karaj plain, Iran
Authors: Alizadeh Maedeh , Noori Roohollah , Omidvar Babak , Nohegar Ahmad , Pistre Severin 
Published: April 2024

AbstractGroundwater pollution by nitrate has is a major concern in the Tehran–Karaj aquifer, Iran, where the wells provide up to 80% of the water supply for a population of more than 18 million—yet detailed human health risks associated with nitrate are unknown due to the lack of accessible data to adequately cover the aquifer in both place and time. Here, using a rich dataset measured annually in more than 75 wells, we mapped the non-carcinogenic risk of nitrate in the aquifer between 2007 and 2018, a window with the most extensive anthropogenic activities in this region. Nitrate concentration varied from ~ 6 to ~ 150 mg/L, around three times greater than the standard level for drinking use, i.e. 50 mg/L. Samples with a non-carcinogenic risk of nitrate, which mainly located in the eastern parts of the study region, threatened children’s health, the most vulnerable age group, in almost all of the years during the study period. Our findings revealed that the number of samples with a positive risk of nitrate for adults decreased in the aquifer from 2007 (17 wells) to 2018 (6 wells). Although we hypothesized that unsustainable agricultural practices, the growing population, and increased industrial activities could have increased the nitrate level in the Tehran-Karaj aquifer, improved sanitation infrastructures helped to prevent the intensification of nitrate pollution in the aquifer during the study period. Our compilation of annually mapped non-carcinogenic risks of nitrate is beneficial for local authorities to understand the high-risk zones in the aquifer and for the formulation of policy actions to protect the human health of people who use groundwater for drinking and other purposes in this densely populated region.
Classifying early infant feeding status from clinical notes using natural language processing and machine learning
Authors: Lemas Dominick J. , Du Xinsong , Rouhizadeh Masoud , Lewis Braeden , Frank Simon , Wright Lauren , Spirache Alex , Gonzalez Lisa , Cheves Ryan , Magalhães Marina , Zapata Ruben , Reddy Rahul , Xu Ke , Parker Leslie , Harle Chris , Young Bridget , Louis-Jaques Adetola , Zhang Bouri , Thompson Lindsay , Hogan William R. , Modave François 
Published: April 2024

AbstractThe objective of this study is to develop and evaluate natural language processing (NLP) and machine learning models to predict infant feeding status from clinical notes in the Epic electronic health records system. The primary outcome was the classification of infant feeding status from clinical notes using Medical Subject Headings (MeSH) terms. Annotation of notes was completed using TeamTat to uniquely classify clinical notes according to infant feeding status. We trained 6 machine learning models to classify infant feeding status: logistic regression, random forest, XGBoost gradient descent, k-nearest neighbors, and support-vector classifier. Model comparison was evaluated based on overall accuracy, precision, recall, and F1 score. Our modeling corpus included an even number of clinical notes that was a balanced sample across each class. We manually reviewed 999 notes that represented 746 mother-infant dyads with a mean gestational age of 38.9 weeks and a mean maternal age of 26.6 years. The most frequent feeding status classification present for this study was exclusive breastfeeding [n = 183 (18.3%)], followed by exclusive formula bottle feeding [n = 146 (14.6%)], and exclusive feeding of expressed mother’s milk [n = 102 (10.2%)], with mixed feeding being the least frequent [n = 23 (2.3%)]. Our final analysis evaluated the classification of clinical notes as breast, formula/bottle, and missing. The machine learning models were trained on these three classes after performing balancing and down sampling. The XGBoost model outperformed all others by achieving an accuracy of 90.1%, a macro-averaged precision of 90.3%, a macro-averaged recall of 90.1%, and a macro-averaged F1 score of 90.1%. Our results demonstrate that natural language processing can be applied to clinical notes stored in the electronic health records to classify infant feeding status. Early identification of breastfeeding status using NLP on unstructured electronic health records data can be used to inform precision public health interventions focused on improving lactation support for postpartum patients.