bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study
Authors: Estrela Tais , Stiebel-Kalish Hadas , Rettenmaier Leigh , Henderson Amanda D. , Sotirchos Elias , Said Yana , Ahmadi Gelareh , Tajfirouz Deena A. , Flanagan Eoin P. , Tisavipat Nanthaya , Gise Ryan , Chwalisz Bart K. , Chen John J. 
Published: July 2024

Background:
Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning.

Methods:
This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC.

Results:
Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = −0.60 and R = −0.64, respectively), inversely moderate in patients with MOGAD (R = −0.34 and R = −0.40, respectively), and weak in patients with NMOSD (R = −0.03 and R = −0.17, respectively).

Conclusions:
Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.
Investigating Combined Hypoxia and Stemness Indices for Prognostic Transcripts in Gastric Cancer: Machine Learning and Network Analysis Approaches
Authors: Mahmoudian-Hamedani Sharareh , Lotfi-Shahreza Maryam , Nikpour Parvaneh 
Published: July 2024

AbstractIntroductionGastric cancer (GC) is among the deadliest malignancies globally, characterized by hypoxia-driven pathways that promote cancer progression, including mechanisms associated with stemness facilitating invasion and metastasis. This study aimed to develop a prognostic decision tree using genes implicated in hypoxia and stemness pathways to predict outcomes in GC patients.Material and MethodsGC RNA-seq data from The Cancer Genome Atlas (TCGA) were utilized to compute hypoxia and stemness scores via Gene Set Variation Analysis (GSVA) and mRNA expression-based stemness index (mRNAsi). Hierarchical clustering based on these scores identified clusters with distinct survival outcomes, and differentially expressed genes (DEGs) between these clusters were identified. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify modules and hub genes associated with clinical traits. Hub genes overlapping with DEGs were extracted, followed by functional enrichment, protein-protein interaction (PPI) network analysis, and survival analysis of shared genes. A prognostic decision tree was constructed using survival-associated genes.ResultsHierarchical clustering identified six clusters among 375 TCGA GC patients, showing significant differences in survival outcomes between cluster 1 (with low hypoxia and high stemness) and cluster 4 (high hypoxia and stemness). Validation in the GSE62254 dataset corroborated these findings. WGCNA revealed modules correlating with clinical traits and survival. Functional enrichment highlighted pathways such as cell adhesion and calcium signaling. The decision tree based on survival-related genes includingAKAP6,GLRB,LINC00578,LINC00968,MIR145,NBEA,NEGR1andRUNX1T1and achieved an area under the curve (AUC) of 0.81 (training) and 0.67 (test), demonstrating the utility of combined scores in patient stratification.ConclusionThis study introduces a novel hypoxia-stemness-based prognostic decision tree for GC. The identified genes show promise as prognostic biomarkers for GC, warranting further validation in clinical settings.
C-terminal CDC42 variants in autoinflammatory patients specifically trigger actin defects and NF-κB hyperactivation
Authors: Iannuzzo Alberto , Mertz Philippe , Delafontaine Selket , Tacine Rachida , Boursier Guilaine , Hentgen Véronique , Georgin-Lavialle Sophie , Meyts Isabelle , Delon Jérôme 
Published: July 2024

BackgroundCDC42 belongs to the RHO GTPases family. Recently, four variants were identified in autoinflammatory patients. One variant affects the N-terminal part of the protein while the three others are located in the C-terminal region. To date, most of the functional defects were only reported for the C-terminal R186C variant. The other three variants are far less characterized at the functional level.ObjectivesWe aimed to investigate whether all four CDC42 variants share common signaling alterations.MethodsWe performed in depth imaging analysis of actin cytoskeleton and NF-κB nuclear translocation, coupled to flow cytometry in cells from patients or in the monocytic THP-1 cell line.ResultsWe show that the N-terminal Y64C CDC42 variant localizes normally in cells and does not exhibit any defect in actin filaments formation or NF-κB activation. By contrast, all three C-terminal CDC42 variants have aberrant subcellular localizations and share common functional alterations. They exhibit a strong reduction or complete block in their abilities to polymerize actin filaments. They also show more NF-κB nuclear translocation and phosphorylation. However, we suggest that there is no causal relationship between these two events. Artificial reduction in cellular actin content using specific pharmacologic drugs is indeed not sufficient to hyperactivate NF-κB.ConclusionsThis study further extends the spectrum of defects observed in autoinflammatory CDC42 patients, and pinpoints a functional heterogeneity between N- and C-terminal CDC42 variants. We also show that CDC42 patients should not be necessarily classified among actinopathies. Altogether, the functional defects we report here can lead the way towards more personalized therapeutic interventions.
Validation of morphological ear classification devised by principal component analysis using three-dimensional images for human identification
Authors: Biwasaka Hitoshi , Usui Akihito , Takamiya Masataka , Angelakopoulos Nikolaos , Cameriere Roberto , Kumagai Akiko 
Published: July 2024

AbstractThis study attempts to classify ear morphology for human identification in forensic investigations by distinguishing between the upper auricle and lobule areas. A three-dimensional homologous model of the ear was created using 414 ear images of males aged 17–93 years reconstructed from computed tomography scans of forensic autopsy cases. Morphological changes were visualized using principal component analysis and areas of significant individual differences within the entire ear were identified. The classification criterion images for the upper auricle (ten images) and lobule (12 images) were developed by combining multiple principal component values: components 1–5 for the upper auricle and 1–6 for the lobule. Three-dimensional ear images of the upper auricle and lobule areas from 414 subjects were categorized using a measurement method based on the minimum distance between 5,507 corresponding points. The results indicate the applicability of the criterion images for the morphological classification of ears in this study.
Circadian clock disruption engages the DREAM complex in suppressing cellular health
Authors: Valentim Isabela Santos , Romero-Expósito Francisco Javier , Schwab Katjana , Bayar Melike , Riege Konstantin , Fischer Martin , Olmedo María , Hoffmann Steve , Ermolaeva Maria A. 
Published: July 2024

AbstractCircadian clock disruption and lack of sleep impair health of cells and organs, but mechanisms remain elusive. Here, we used multi-omics, molecular and functional assays in three model systems (C. elegans, human retinal cells and mouse brain) to identify the DREAM complex as a ubiquitous health repressor acting downstream of clock impairment. We show that clock dysfunction aberrantly activates DREAM leading to simultaneous de-regulation of multiple cellular processes. The affected activities including translation, stress responses and OXPHOS are basic and ubiquitous, explaining pan-cellular decline induced by impaired clock and sleep. Accordingly, inhibition of DREAM restores healthy homeostasis and alleviates de-regulation of adaptive mechanisms in clock-impaired nematodes and human cells. This restorative effect occurs amid persisting clock dysfunction, suggesting that DREAM ablation uniquely uncouples circadian clock impairments from their negative effects on health. Our study coins DREAM as a new therapeutic target for preserving organismal fitness under re-current circadian dysfunction.
Hornworts reveal a spatial model for pyrenoid-based CO2-concentrating mechanisms in land plants
Authors: Robison Tanner A. , Oh Zhen Guo , Lafferty Declan , Xu Xia , A. Villarreal Juan Carlos , Gunn Laura H. , Li Fay-Wei 
Published: July 2024

ABSTRACTPyrenoid-based CO2-concentrating mechanisms (pCCMs) turbocharge photosynthesis by saturating CO2around Rubisco. Hornworts are the only land plants with a pCCM. Owing to their closer relationship to crops, hornworts could offer greater translational potential compared to the green alga Chlamydomonas, the traditional model for studying pCCM. Here we report the first thorough investigation of a hornwort pCCM using the emerging modelAnthoceros agrestis. The pyrenoids inA. agrestisexhibit liquid-like properties similar to Chlamydomonas, but differ by lacking starch sheaths and being enclosed by multiple thylakoids. We found that the core pCCM components in Chlamydomonas, including BST, LCIB, and CAH3, are conserved inA. agrestisand likely have similar functions based on their subcellular localizations. Therefore, the underlying chassis for concentrating CO2might be shared between hornworts and Chlamydomonas, and ancestral to land plants. Our study presents the first spatial model for pCCM in a land plant, paving the way for future biochemical and genetic investigations.
Ultra-fast variant effect prediction using biophysical transcription factor binding models
Authors: Hosseini Rezwan , Balci Ali Tugrul , Kostka Dennis , Chikina Maria 
Published: July 2024

AbstractSequence variation within TF binding sites can significantly affect TF-DNA interactions, influencing gene expression and contributing to disease susceptibility or phenotypic traits. Despite recent progress in deep sequence-to-function models that predict functional output from sequence data, these methods perform inadequately on some variant effect prediction tasks, especially with common genetic variants. This limitation underscores the importance of leveraging biophysical models of TF binding to enhance interpretability of variant effect scores and facilitate mechanistic insights.We introducemotifDiff, a novel computational tool designed to quantify variant effects using mono and dinucleotide position weight matrices.motifDiffoffers several key advantages, including scalability to score millions of variants within minutes, implementation of various normalization strategies for optimal performance, and support for both dinucleotide and mononucleotide models. We demonstratemotifDiff‘s efficacy by evaluating it across diverse ground truth datasets that quantify the effects of common variants in vivo, thereby establishing robust benchmarks for the predictive value of variant effect calculations.motifDiffis available as a standalone Python application athttps://github.com/rezwanhosseini/MotifDiff.
Lethal Disruption of the Symbiotic Gut Community in Eastern Subterranean Termite Caused by Boric Acid
Authors: Ashbrook Aaron R. , Schwarz Melbert , Schal Coby , Mikaelyan Aram 
Published: July 2024

AbstractThe Eastern subterranean termite,Reticulitermes flavipes(Kollar), is a significant pest, causing extensive damage to structures that amount to substantial economic losses. Traditional termite control methods have utilized boric acid, known for its broad-spectrum insecticidal properties, yet its impact on termite gut microbiomes and the implications of such effects remain understudied. Our study evaluates the dose-dependent mortality ofR. flavipesupon being provided boric acid treated filter papers and investigates the resulting dysbiosis within the termite gut microbiome. Consistent with reports from other insects, mortality increased in a dose-dependent manner, with the highest boric acid concentration (203.7 µg/cm2of filter paper) significantly reducing termite survival. 16S rRNA gene sequencing of the gut microbiome revealed notable shifts in composition, indicating boric acid-induced dysbiosis. Aside from an overall decrease in microbial diversity, the relative abundance of some symbionts essential for termite nutrition decreased in response to higher boric acid concentrations, while several putative pathogens increased. Our findings extend the understanding of boric acid’s mode of action in termites, emphasizing its effect beyond direct toxicity to include significant microbiome modulation that can have dire effects on termite biology. Considering its potential to induce dysbiosis and potentially augment the effectiveness of entomopathogens, our study supports the continued use of boric acid and related compounds for termite-resistant treatments for wood.
Loss of neurofibromin accelerates uveal and dermal melanoma formation driven by GNAQ
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D. 
Published: July 2024

ABSTRACTNeurofibromin is a very large and complex tumor suppressor, whose loss can synergize with other MAPK pathway mutations to promote melanoma in the skin. In this paper, we investigated whetherNF1loss has a role in other melanomas, such as those that form in the dermis or eye (uveal tract). We found that heterozygous 17q11.2 loss that includes theNF1locus is an uncommon, but recurrent phenomenon in human dermal and uveal melanomas described previously. We studied the effects ofNf1haploinsufficiency in mice expressing oncogenic GNAQQ209Lin melanocytes and Schwann cells of peripheral nerves using thePlp1-creERTtransgene, with tamoxifen given at 5 weeks of age.Nf1haploinsufficiency accelerated dermal and uveal melanoma formation. We studied the effects ofNf1loss in these melanomas using RNAseq. Many of the differentially expressed genes were homologous to genes whose expression correlates with prognosis in human uveal melanoma. Of particular interest was the up-regulation of cAMP signaling and its connection to protein kinase A, which is mutant in malignant melanotic nerve sheath tumors (MMNSTs). An unexpected finding was that oncogenic GNAQ was sufficient by itself to drive peripheral nerve sheath-like neoplasms in the mice. Hence, these studies reveal new insight into both melanocyte and Schwann cell transformation.
Dual roles of idling moments in past and future memories
Authors: Ghandour Khaled , Haga Tatsuya , Ohkawa Noriaki , Fung Chi Chung Alan , Nomoto Masanori , Fayed Mostafa R. , Asai Hirotaka , Sato Masaaki , Fukai Tomoki , Inokuchi Kaoru 
Published: July 2024

AbstractEvery day, we experience new daily episodes and store new memories. Although memories are stored in corresponding engram cells, how different sets of engram cells are selected for current and next episodes, and how they create their memories, remains unclear. We report that in mice, hippocampal CA1 neurons show an organized synchronous activity in prelearning home cage sleep that correlates with the learning ensembles only in engram cells, termed preconfigured ensembles. Moreover, after learning, a subset of nonengram cells develops population activity, which is constructed during postlearning offline periods through synaptic depression and scaling, and then emerges to represent engram cells for new learning. Together, our findings indicate that during offline periods there are two parallel processes occurring: conserving of past memories through reactivation, and preparation for upcoming ones through offline synaptic plasticity mechanisms.
LINC01432binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy
Authors: Mishra Richa , Thunuguntla Prasanth , Perkin Alani , Duraiyan Dhanusha , Bagwill Katelyn , Gonzales Savannah , Brizuela Vanessa , Daly Steve , Chang Yoon Jae , Abebe Mahdote , Rajana Yash , Wichmann Kelly , Bolick Catheryn , King Jaiyana , Fiala Mark , Fortier Julie , Jayasinghe Reyka , Schroeder Mark , Ding Li , Vij Ravi , Silva-Fisher Jessica 
Published: July 2024

AbstractMultiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression- free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA,LINC01432. We investigatedLINC01432overexpression and CRISPR/Cas9 knockdown in MM cell lines to show thatLINC01432overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show thatLINC01432directly interacts with the RNA binding protein, CELF2. Lastly, we showed thatLINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterizedLINC01432,which inhibits apoptosis.Key points:lncRNA expression was found to be dysregulated in patients with short PFS to standard multiple myeloma therapy.LINC01432-bound CELF2 inhibits apoptosis.
Network for Knowledge Organization (NEKO): an AI knowledge mining workflow for synthetic biology research
Authors: Xiao Zhengyang , Pakrasi Himadri B. , Chen Yixin , Tang Yinjie J. 
Published: July 2024

AbstractLarge language models (LLMs) can complete general scientific question-and-answer, yet they are constrained by their pretraining cut-off dates and lack the ability to provide specific, cited scientific knowledge. Here, we introduceNetwork forKnowledgeOrganization (NEKO), a workflow that uses LLM Qwen to extract knowledge through scientific literature text mining. When user inputs a keyword of interest, NEKO can generate knowledge graphs and comprehensive summaries from PubMed search. NEKO has immediate applications in daily academic tasks such as education of young scientists, literature review, paper writing, experiment planning/troubleshooting, and new hypothesis generation. We exemplified this workflow’s applicability through several case studies on yeast fermentation and cyanobacterial biorefinery. NEKO’s output is more informative, specific, and actionable than GPT-4’s zero-shot Q&A. NEKO offers flexible, lightweight local deployment options. NEKO democratizes artificial intelligence (AI) tools, making scientific foundation model more accessible to researchers without excessive computational power.
Eruptive insect outbreaks from endemic populations under climate change
Authors: Brush Micah , Lewis Mark A. 
Published: July 2024

AbstractInsects, especially forest pests, are frequently characterized by eruptive dynamics. These types of species can stay at low, endemic population densities for extended periods of time before erupting in large-scale outbreaks. We here present a mechanistic model of these dynamics for mountain pine beetle. This extends a recent model that describes key aspects of mountain pine beetle biology coupled with a forest growth model by additionally including a fraction of low-vigor trees. These low-vigor trees, which may represent hosts with weakened defenses from drought, disease, other bark beetles, or other stressors, give rise to an endemic equilibrium in biologically plausible parameter ranges. The mechanistic nature of the model allows us to study how each model parameter affects the existence and size of the endemic equilibrium. We then show that under certain parameter shifts that are more likely under climate change, the endemic equilibrium can disappear entirely, leading to an outbreak.
Development and validation of the Emotion Regulation Questionnaire – Positive/Negative (ERQ-PN): Does the target of emotion regulation matter?
Authors: De Jesús-Romero Robinson , Chimelis-Santiago José R. , Rutter Lauren A. , Lorenzo-Luaces Lorenzo 
Published: July 2024

AbstractThe Emotion Regulation Questionnaire (ERQ) assesses emotion regulation strategies, particularly expressive suppression and cognitive reappraisal. However, the ERQ does not discern between regulating positive vs. negative emotions. Recent research suggests that suppression and reappraisal can impact mental health differently when targeting positive vs negative emotions. We developed and validated the Emotion Regulation Questionnaire - Positive/Negative (ERQ-PN), designed to measure positive and negative forms of suppression and reappraisal strategies. We recruited 963 participants (female = 478) through Prolific.com and administered the ERQ-PN. Participants had an average age of 45 years and were predominantly White (74%) and heterosexual (84%). Structural validity was assessed through confirmatory factor analyses. Model fit was estimated using the comparative fit index and the root-mean-square error of approximation. We also used the Bayesian information criterion to compare the fit of different models. Overall, participants used reappraisal more often to decrease negative emotions (vs. increasing positive) and leaned toward using suppression more for negative (vs. positive) emotions. These analyses revealed that the four-factor model (Model 2) delineating four latent variables (positive reappraisal, negative reappraisal, positive suppression, and negative suppression) had a good fit (RMSEA = 0.07, CFI = 0. 97, TLI = 0.96,χ2(98) = 531.28,p< 0.001). An incremental validity assessment revealed that positive and negative reappraisal correlated similarly with related mental health constructs. By contrast, suppression of negative vs. positive emotions was differentially associated to the validators tested. The ERQ-PN represents a valid measure of emotion regulation that accounts for both positive and negative emotions.