bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scene context and attention independently facilitate MEG decoding of object category
Authors: Leticevscaia Olga , Brandman Talia , Peelen Marius V. 
Published: July 2024

AbstractMany of the objects we encounter in our everyday environments would be hard to recognize without any expectations about these objects. For example, a distant silhouette may be perceived as a car because we expect objects of that size, positioned on a road, to be cars. Reflecting the influence of such expectations on visual processing, neuroimaging studies have shown that when objects are poorly visible, expectations derived from scene context facilitate the representations of these objects in visual cortex from around 300 ms after scene onset. The current magnetoencephalography (MEG) study tested whether this facilitation occurs independently of attention and task relevance. Participants viewed degraded objects alone or within their original scene context while they either attended the scenes (attended condition) or the fixation cross (unattended condition), temporally directing attention away from the scenes. Results showed that at 300 ms after stimulus onset, multivariate classifiers trained to distinguish clearly visible animate vs inanimate objects generalized to distinguish degraded objects in scenes better than degraded objects alone, despite the added clutter of the scene background. Attention also modulated object representations at this latency, with better category decoding in the attended than the unattended condition. The modulatory effects of context and attention were independent of each other. Finally, data from the current study and a previous study were combined (N=51) to provide a more detailed temporal characterization of contextual facilitation. These results extend previous work by showing that facilitatory scene-object interactions are independent of the specific task performed on the visual input.
PTEN Regulates Myofibroblast Activation in Valvular Interstitial Cells based on Subcellular Localization
Authors: Batan Dilara , Tseropoulos Georgios , Kirkpatrick Bruce E. , Bera Kaustav , Khang Alex , Weiser-Evans Mary , Anseth Kristi S. 
Published: July 2024

AbstractAortic valve stenosis (AVS) is characterized by altered mechanics of the valve leaflets, which disrupts blood flow through the aorta and can cause left ventricle hypotrophy. These changes in the valve tissue result in activation of resident valvular interstitial cells (VICs) into myofibroblasts, which have increased levels of αSMA in their stress fibers. The persistence of VIC myofibroblast activation is a hallmark of AVS. In recent years, the tumor suppressor gene phosphatase and tensin homolog (PTEN) has emerged as an important player in the regulation of fibrosis in various tissues (e.g., lung, skin), which motivated us to investigate PTEN as a potential protective factor against matrix-induced myofibroblast activation in VICs. In aortic valve samples from humans, we found high levels of PTEN in healthy tissue and low levels of PTEN in diseased tissue. Then, using pharmacological inducers to treat VIC cultures, we observed PTEN overexpression prevented stiffness-induced myofibroblast activation, whereas genetic and pharmacological inhibition of PTEN further activated myofibroblasts. We also observed increased nuclear PTEN localization in VICs cultured on stiff matrices, and nuclear PTEN also correlated with smaller nuclei, altered expression of histones and a quiescent fibroblast phenotype. Together, these results suggest that PTEN not only suppresses VIC activation, but functions to promote quiescence, and could serve as a potential pharmacological target for the treatment of AVS.
Tissue-specific immune transcriptional signatures in the bordering tissues of the mouse brain and retina
Authors: Etebar Fazeleh , Whatmore Paul , Harkin Damien G. , Dando Samantha J. 
Published: July 2024

AbstractBackgroundBordering the central nervous system (CNS) parenchyma are the pia mater (the innermost layer of the meninges enveloping the brain) and the choroid (underlying the retina). While near the neural parenchyma, the pia mater and choroid are external to the immune privileged environment of the brain and retina and thus are distinct immune compartments. This study aimed to characterise the transcriptomic signatures of immune cells within the pia mater and choroid bordering the healthy adult mouse CNS.MethodsBrains and eyes were obtained from 7-week-old female C57Bl/6J mice. Pia mater-enriched tissue and choroid were dissected and processed for fluorescence activated cell sorting of CD45+immune cells and single cell RNA-sequencing. Additionally, single cell RNA-sequencing was performed on immune cells isolated from choroid obtained from human donor eye tissue. Immunostaining and confocal microscopy of wholemount tissue were used to validate selected immune cell populationsin situ.ResultsA total of 3,606 cells were sequenced from mouse tissues, including 1,481 CD45+cells from pia mater-enriched tissue and 2,125 CD45+cells from choroid. Clustering and differential gene expression analysis revealed heterogeneous subtypes of monocytes/macrophages, dendritic cells, T cells and B cells. While some clusters were common to both pia mater and choroid, others exhibited tissue-specific gene expression profiles and potential functional specialisations. Analysis of 6,501 CD45+ cells sequenced from human choroid identified similar immune cell populations to mouse choroid.ConclusionsThis study provides a detailed characterisation of the molecular signatures of immune cells within the vascular connective tissues bordering the healthy brain and retina, and their potential roles in immune protection.
Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer
Authors: He Yinghao , Liu Fuqiang , Jiang Zheng 
Published: July 2024

AbstractColon cancer, as a highly prevalent malignant tumor globally, poses a significant threat to human health. In recent years, ferroptosis and cuproptosis, as two novel forms of cell death, have attracted widespread attention for their potential roles in the development and treatment of colon cancer. However, the investigation into the subtypes and their impact on the survival of colon cancer patients remains understudied. In this study, utilizing data from TCGA and GEO databases, we examined the expression differences of ferroptosis and cuproptosis-related genes in colon cancer and identified two subtypes. Through functional analysis and bioinformatics methods, we elucidated pathway differences and biological characteristics between these two subtypes. By leveraging differential genes between the two subtypes, we constructed a prognostic model using univariate Cox regression and multivariate Cox regression analysis as well as LASSO regression analysis. Further survival analysis and receiver operating characteristic curve analysis demonstrated the model’s high accuracy. To enhance its clinical utility, we evaluated the clinical significance of the model and constructed a nomogram, significantly improving the predictive ability of the model and providing a new tool for prognostic assessment of colon cancer patients. Subsequently, through immune-related analysis, we revealed differences in immune cell infiltration and immune function between high- and low-risk groups. Further analysis of the relationship between the model and immune cells and functions revealed potential therapeutic targets. Drug sensitivity analysis revealed associations between the expression of model-related genes and drug sensitivity, suggesting their involvement in tumor resistance through certain mechanisms. AZD8055_1059, Bortezomib_1191, Dihydrorotenone_1827, and MG-132_1862 were more sensitive in the high-risk group. Finally, we analyzed differential expression of model-related genes between tumor tissues and normal tissues, validated through real-time quantitative PCR. In summary, our study provides a relatively accurate prognostic tool for colon cancer patients, offering guidance for treatment selection and indicating the potential of immunotherapy in colon cancer.
Geometry based gene expression signatures detect cancer treatment responders in clinical trials
Authors: Chachólski Wojciech , Ramanujam Ryan 
Published: July 2024

AbstractAimThe overall aim of this project is to determine if gene expression signatures of tumors, constructed from geometrical attributes of data, could be used to predict patient treatment response by detecting subgroups of responders. This is tested in Pfizer clinical trial data and compared with standard clustering methods (n= 726).ResultsGeometrical gene expression signature analysis demonstrated high utility to detect sub-groups with enhanced treatment response. In the Pfizer trial, gene expression signatures were able to detect three subgroups of responders (p= 0.012), containing 52.9% of patients and accounting for nearly all the observed treatment effect. Standard techniques following a similar methodology were able to partition a single subgroup containing 21.3% of patients.ConclusionsGene expression based geometrical signatures yielded vastly superior performance over standard clustering techniques, as demonstrated in Pfizer’s Phase III clinical trial data. These can be used to determine subgroups of enhanced treatment response in oncology clinical trials, and might lead to personalized treatment recommendations in the future.
Social predation by a nudibranch mollusc
Authors: Otter Kate , Gomidova Saida , Katz Paul S. 
Published: July 2024

AbstractSocial predation is a common strategy used by predators to subdue and consume prey. Animals that use this strategy have many ways of finding each other, organizing behaviors and consuming prey. There is wide variation in the extent to which these behaviors are coordinated and the stability of individual roles. This study characterizes social predation by the nudibranch mollusc,Berghia stephanieae, which is a specialist predator that eats only the sea anemone,Exaiptasia diaphana. A combination of experimental and modeling approaches showed thatB. stephanieaedoes predate uponE. diaphanain groups. The extent of social feeding was not altered by length of food deprivation, suggesting that animals are not shifting strategies based on internal state. It was unclear what cues the individualBerghiaused to find each other; choice assays testing whether they followed slime trails, were attracted to injured anemones, or preferred conspecifics feeding did not reveal any cues. Individuals did not exhibit stable roles, such as leader or follower, rather the population exhibited fission-fusion dynamics with temporary roles during predation. Thus, theBerghiaprovides an example of a specialist predator of dangerous prey that loosely organizes social feeding, which persists across hunger states and uses temporary individual roles; however, the cues that it uses for aggregation are unknown.Significance StatementSocial predation is a strategy to hunt dangerous prey and minimize injury. Many nudibranchs specialize as predators of cnidarians, which are dangerous to them. Although nudibranchs are typically characterized as solitary hunters, we provide evidence that social predation strategies may be used by a species that specializes on one species of sea anemone. The study showed that the individual sea slugs assumed temporary roles for establishing groups and that the group dynamics were unstable. However, the cues that the nudibranchs use to aggregate remain elusive.
Speciation completion rates have limited impact on macroevolutionary diversification
Authors: Veron Pierre , Andréoletti Jérémy , Giraud Tatiana , Morlon Hélène 
Published: July 2024

AbstractStandard birth-death processes used in macroevolutionary studies assume instantaneous speciation, an unrealistic premise that limits the interpretation of speciation and extinction rates. The protracted birth-death (PBD) model instead assumes that speciation involves two steps: initiation and completion. In order to understand their respective influence on macroevolutionary speciation rates, we compute a standard time-varying birth-death scenario that is “equivalent” to the PBD model in terms of speciation and extinction probabilities. First, we find a sharp decline in the equivalent birth rate near the present, indicating that rates estimated at the tips of phylogenies may not accurately reflect the underlying speciation process. Second, the completion rate controls the timing of the decay rather than the asymptotic equivalent rates. The equivalent birth rate in the past scales with the speciation initiation rate, with a scaling factor depending mostly on the population extinction rate. Our results suggest that the rates of population formation and extinction may often play a larger role than the speed of accumulation of reproductive isolation in modulating speciation rates. Our study establishes a theoretical framework for understanding how microevolutionary processes combine to explain the diversification of species on macroevolutionary time scales.
Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization
Authors: Saito Junichi , Dave Jui M. , Gallardo-Vara Eunate , Kabir Inamul , Tellides George , Riemer Robert K. , Urban Zsolt , Hla Timothy , Greif Daniel M. 
Published: July 2024

AbstractDefective elastin and smooth muscle cell (SMC) accumulation characterize both arterial diseases (e.g., atherosclerosis, restenosis and supravalvular aortic stenosis [SVAS]), and physiological ductus arteriosus (DA) closure. Elastin deficiency induces SMC hyperproliferation; however, mechanisms underlying this effect are not well elucidated. Elastin (ELN) is expressed from embryonic day (E) 14 in the mouse aorta. Immunostains ofEln(+/+)andEln(-/-)aortas indicate that SMCs of theElnnull aorta are first hyperproliferative at E15.5, prior to morphological differences. Bulk RNA-seq reveals that sphingosine kinase 1 (Sphk1) is the most upregulated transcript inEln(-/-)aortic SMCs at E15.5. Reduced ELN increases levels of transcription factor early growth response 1 (EGR1), resulting in increased SPHK1 levels in cultured human aortic SMCs and in the mouse aorta at E15.5 and P0.5. Aortic tissue from Williams-Beuren Syndrome patients, who have elastin insufficiency and SVAS, also has upregulated SPHK1 expression. SMC-specificSphk1deletion or pharmacological inhibition of SPHK1 attenuates SMC proliferation and mitigates aortic disease, leading to extended survival ofEln(-/-)mice. In addition, EGR1 and SPHK1 are increased in the wild-type mouse DA compared to adjacent descending aorta. Treatment with a SPHK1 inhibitor attenuates SMC proliferation and reduces SMC accumulation, leading to DA patency. In sum, SPHK1 is a key node in elastin deficiency-induced hypermuscularization, and inhibiting this kinase may be a therapeutic strategy for SVAS and select congenital heart diseases in which a patent DA maintains circulation.One Sentence SummarySphingosine kinase 1-induced by defective elastin promotes muscularization in pathological aortic stenosis and physiological ductus arteriosus occlusion.
Development of a Deep Learning model Tailored for HER2 Detection in Breast Cancer to aid pathologists in interpreting HER2-Low cases
Authors: Bannier Pierre-Antoine , Broeckx Glenn , Herpin Loïc , Dubois Rémy , Praet Lydwine Van , Maussion Charles , Deman Frederik , Amonoo Ellen , Mera Anca , Timbres Jasmine , Gillett Cheryl , Sawyer Elinor , Gazińska Patrycja , Ziolkowski Piotr , Lacroix-Triki Magali , Salgado Roberto , Irshad Sheeba 
Published: July 2024

AbstractIntroductionOver 50% of breast cancer cases are "Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC)", characterized by HER2 immunohistochemistry (IHC) scores of 1+ or 2+ alongside no amplification on fluorescence in situ hybridization (FISH) testing. The development of new anti-HER2 antibody-drug conjugates (ADCs) for treating HER2-low breast cancers illustrates the importance of accurately assessing HER2 status, particularly HER2-low breast cancer. In this study, we evaluated the performance of a deep learning (DL) model for the assessment of HER2, including an assessment of the causes of discordances of HER2-Null between a pathologist and the DL model. We specifically focussed on aligning the DL model rules with the ASCO/CAP guidelines, including stained cells’ staining intensity and completeness of membrane staining.MethodsWe trained a DL model on a multi-centric cohort of breast cancer cases with HER2- immunohistochemistry scores (n=299). The model was validated on 2 independent multi- centric validation cohorts (n=369 and n=92), with all cases reviewed by 3 senior breast pathologists. All cases underwent a thorough review by three senior breast pathologists, with the ground truth determined by a majority consensus on the final HER2 score among the pathologists. In total, 760 breast cancer cases were utilized throughout the training and validation phases of the study.ResultsThe model’s concordance with the ground truth (ICC = 0.77 [0.68 - 0.83]; Fisher P = 1.32e-10) is higher than the average agreement among the 3 senior pathologists (ICC = 0.45 [0.17 - 0.65]; Fisher P = 2e-3). In the two validation cohorts, the DL model identifies 95% [93%- 98%] and 97% [91% - 100%] of HER2-low and HER2-positive tumors respectively. Discordant results were characterized by morphological features such as extended fibrosis, a high number of tumor-infiltrating lymphocytes, and necrosis, whilst some artifacts such as non- specific background cytoplasmic stain in the cytoplasm of tumor cells also cause discrepancy.ConclusionDeep learning can support pathologists’ interpretation of difficult HER2-low cases. Morphological variables and some specific artifacts can cause discrepant HER2-scores between the pathologist and the DL Model.
Cognitive neuropsychological and neuroanatomic predictors of naturalistic action performance in left hemisphere stroke: a retrospective analysis
Authors: Thibault Simon , Wong Aaron L. , Buxbaum Laurel J. 
Published: July 2024

AbstractIndividuals who have experienced a left hemisphere cerebrovascular accident (LCVA) have been shown to make errors in naturalistic action tasks designed to assess the ability to perform everyday activities such as preparing a cup of coffee. Naturalistic action errors in this population are often attributed to limb apraxia, a common deficit in the representation and performance of object-related actions. However, naturalistic action impairments are also observed in right hemisphere stroke and traumatic brain injury, populations infrequently associated with apraxia, and errors across all these populations are influenced by overall severity. Based on these and other data, an alternative (though not mutually exclusive) account is that naturalistic action errors in individuals with LCVA are also a consequence of deficits in general attentional resource availability or allocation. In this study, we conducted a retrospective analysis of data from a group of 51 individuals with LCVA who had completed a test of naturalistic action, along with a battery of tests assessing praxis, attention allocation and control, reasoning, and language abilities to determine which of these capacities contribute uniquely to naturalistic action impairments. Using a regularized regression method, we found that naturalistic action impairments are predicted by both praxis deficits (hand posture sequencing and gesture recognition), as well as attention allocation and control deficits (orienting and dividing attention), along with language comprehension ability and age. Using support vector regression-lesion symptom mapping, we demonstrated that naturalistic action impairments are associated with lesions to posterior middle temporal gyrus and anterior inferior parietal lobule regions known to be implicated in praxis; as well the middle frontal gyrus that has been implicated in both praxis and attention allocation and control. Together, these findings support the hypothesis that naturalistic action impairments in people with LCVA are a consequence of apraxia as well as deficits in attention allocation and control.
Fgf23 expression increases atherosclerotic plaque burden in maleApoEdeficient mice
Authors: Lindberg Karolina , Ovchinnikova Olga , Moor Matthias B. , Pirault John , Ketelhuth Daniel FJ , Olauson Hannes , Hansson Göran K. , Larsson Tobias E. 
Published: July 2024

AbstractIntroductionComponents of both the innate and adaptive immune system impact on arterial walls in atherosclerosis. Fibroblast growth factor-23 (FGF23) is a phosphate regulating hormone linked to cardiovascular disease (CVD) in patients with and without chronic renal disease. However, it remains controversial whether FGF23 is merely a biomarker or contributes to CVD. Here, we overexpressed FGF23 inApoE-/-mice to delineate the role of FGF23 in atherogenesis.Methods and Results10-week oldApoE-/-mice received a hydrodynamic tail vein with a plasmid encoding for Fgf23, and were sacrificed 10 weeks later. Fgf23 concentrations increased more than 400-fold in the Fgf23 treated group, remaining high throughout the experiment. Mice in the Fgf23 group developed hypophosphatemia, secondary hyperparathyroidism and a moderate increase in plasma creatinine concentrations. MaleApoE-/-mice exposed to high Fgf23 developed larger atherosclerotic lesions compared to controls, in two different locations of aorta, whereas no differences in plaque burden were seen between femaleApoE-/-mice and controls. Serum IL-6 concentrations were increased in the Fgf23 group, associated with a vascular inflammatory response of recruited macrophages and neutrophils, and with a shift of CD4+ T effector cells from Th1 to Th17 and migration of lymphocytes to the spleen.ConclusionFgf23 increases the atherosclerotic burden in maleApoE-/-mice and alters both the innate immune system and T cell subpopulations, generating an inflammatory environment that may promote adverse clinical outcomes associated with Fgf23 excess.