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Localizing the 'multiple-demand' frontoparietal network in individual subjects [article]

Sneha Shashidhara, Floortje S. Spronkers, Yaara Erez
2019 bioRxiv   pre-print
Acknowledgements This work was funded by a Royal Society Dorothy Hodgkin Research Fellowship (UK) to Yaara Erez (DH130100).  ...  and Duncan 2015; Shashidhara and Erez 2019 ).  ...  and Duncan 2015; Blank et al. 2014; Blank and Fedorenko 2017; Woolgar and Zopf 2017; Mineroff et al. 2018; Shashidhara and Erez 2019) .  ... 
doi:10.1101/661934 fatcat:j35wlkap35hdlfxfewgnmsrgp4

Reward motivation modulates representation of behaviorally-relevant information across the frontoparietal cortex [article]

Sneha Shashidhara, Yaara Erez
2019 bioRxiv   pre-print
Motivation has been shown to improve behavioral performance across multiple cognitive tasks, yet the underlying neural mechanisms that link motivation and control processes remain unclear. Here, we used functional magnetic resonance imaging (fMRI) in 24 human volunteers (13 females) to test whether reward motivation enhances the representation of task-relevant content across the cognitive control frontoparietal network. In a cued-detection categorization task, participants detected whether an
more » ... ject from a cued visual category was present in a subsequent display. Some of the objects could serve as targets depending on the cued category, therefore highly competed for attention, while others were never cued. Half of all trials offered the possibility of a substantial reward. Multivariate pattern analysis (MVPA) showed a competition-contingent enhancement effect of reward across the MD network. Reward increased the discrimination between highly competing task-relevant categories, but not between less conflicting distinctions. This selective effect was not driven by visual differences. In contrast, Reward did not modulate task-related category distinctions in the high visual region, the lateral occipital complex (LOC). These findings provide evidence that reward leads to selective enhancement of task-relevant information representation across the MD network, suggesting a facilitative effect of reward motivation on efficient allocation of attentional resources.
doi:10.1101/609537 fatcat:ymxnsk7a6jeqfoydhv4kzol3au

Same Story, Different Story

Yaara Yeshurun, Stephen Swanson, Erez Simony, Janice Chen, Christina Lazaridi, Christopher J. Honey, Uri Hasson
2017 Psychological Science  
doi:10.1177/0956797616682029 pmid:28099068 pmcid:PMC5348256 fatcat:tihdgsgrvneyndzcaoo6aa75wy

Prefrontal neural dynamics for behavioral decisions and attentional control [article]

Yaara Erez, Mikiko Kadohisa, Philippe Petrov, Natasha Sigala, Mark J. Buckley, Makoto Kusunoki, John Duncan
2020 bioRxiv   pre-print
Complex neural dynamics in the prefrontal cortex contribute to context-dependent decisions and attentional competition. To analyze these dynamics, we apply demixed principal component analysis to activity of a primate prefrontal cell sample recorded in a cued target detection task. The results track dynamics of cue and object coding, feeding into movements along a target present-absent decision axis in a low-dimensional subspace of population activity. For a single stimulus, object and cue
more » ... g are seen mainly in the contralateral hemisphere. Later, a developing decision code in both hemispheres may reflect interhemispheric communication. With a target in one hemifield and a competing distractor in the other, each hemisphere initially encodes the contralateral object, but finally, decision coding is dominated by the task-relevant target. Tracking complex neural events in a low-dimensional activity subspace illuminates information flow towards task-appropriate behavior, unravelling mechanisms of prefrontal computation.
doi:10.1101/2020.05.06.080325 fatcat:6zbwr4yvnzeptedt7rak5tupyu

An Integrated Neural Framework for Dynamic and Static Face Processing

Michal Bernstein, Yaara Erez, Idan Blank, Galit Yovel
2018 Scientific Reports  
Faces convey rich information including identity, gender and expression. Current neural models of face processing suggest a dissociation between the processing of invariant facial aspects such as identity and gender, that engage the fusiform face area (FFA) and the processing of changeable aspects, such as expression and eye gaze, that engage the posterior superior temporal sulcus face area (pSTS-FA). Recent studies report a second dissociation within this network such that the pSTS-FA, but not
more » ... the FFA, shows much stronger response to dynamic than static faces. The aim of the current study was to test a unified model that accounts for these two functional characteristics of the neural face network. In an fMRI experiment, we presented static and dynamic faces while subjects judged an invariant (gender) or a changeable facial aspect (expression). We found that the pSTS-FA was more engaged in processing dynamic than static faces and changeable than invariant aspects, whereas the OFA and FFA showed similar response across all four conditions. These findings support an integrated neural model of face processing in which the ventral areas extract form information from both invariant and changeable facial aspects whereas the dorsal face areas are sensitive to dynamic and changeable facial aspects. Faces generate highly selective responses in high-level visual cortex. In particular, three face-selective areas are typically revealed, the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus face area (pSTS-FA) 1 . The functional characterization of these areas has been the focus of investigation of numerous studies 2,3 . According to the current dominant model 1,4 the FFA is primarily engaged with the processing of invariant facial aspects (e.g., identity) whereas the pSTS-FA is primarily engaged with the processing of changeable facial aspects (e.g., expression, see Fig. 1a ). Whereas this model is primarily based on studies that presented static faces, recent studies that used dynamic stimuli (i.e. moving faces) revealed that the pSTS-FA and the inferior frontal gyrus face area (IFG-FA), but not the OFA and FFA, show higher response to dynamic (motion) than static (form) faces 5-7 . These findings are consistent with a model suggested by O'toole and colleagues 8 , which highlights the role of the pSTS-FA in the processing of dynamic faces (Fig. 1b) . To integrate these two related functional characterizations of the face network, we have recently proposed a comprehensive neural model of face processing 2,9 (Fig. 2) according to which the dorsal face areas, including the pSTS-FA and IFG-FA, are engaged in the processing of facial motion and also in the processing of changeable facial aspects. This suggestion is based on behavioral studies showing that expression processing benefits from dynamic information more than identity processing 10-13 . In contrast, the ventral face areas, including the OFA and FFA, are engaged in the processing of facial form, and thus are recruited when processing both changeable and invariant facial aspects for both dynamic and static faces. Additionally, based on previous findings of structural and functional connectivity among the face areas 14-16 we suggested that the OFA is primarily connected to the FFA but not to the pSTS-FA. Here, we provide the first direct test of this model. We used a factorial design that crossed task requirements for processing either an invariant (i.e., gender) or a changeable facial aspect (i.e., expression) with face stimuli that either contained motion information in them or did not (Fig. 3) . We assessed the fMRI responses to these different tasks and stimuli classes in the ventral and dorsal face areas, as well as the motion area, MT. This design allowed us to test the following three hypotheses regarding the division of labor between the dorsal and ventral face-processing pathways (see Fig. 4 ): (i) if the primary division of labor is to changeable vs. invariant facial Published: xx xx xxxx OPEN 2 SCientifiC REPORTS | (2018) 8:7036 |
doi:10.1038/s41598-018-25405-9 pmid:29728577 pmcid:PMC5935689 fatcat:gykqjcvkcbedvdm7am3rtvp65a

Generalized framework for stimulus artifact removal

Yaara Erez, Hadass Tischler, Anan Moran, Izhar Bar-Gad
2010 Journal of Neuroscience Methods  
Full details of the experimental protocol appear elsewhere (Erez et al., 2009) .  ...  ., 2000; Erez et al., 2009) to electrical macro-stimulation (Hashimoto et al., 2003; Carlson et al., 2010) and magnetic stimulation (Moliadze et al., 2003; Strafella et al., 2004) .  ... 
doi:10.1016/j.jneumeth.2010.06.005 pmid:20542059 fatcat:7woj6cd3azeujbrltbimzws43e

Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years [article]

Noa Eliakim Raz, Amos Stemmer, Yaara Leibovici-Weissman, Asaf Ness, Muhammad Awwad, Nassem Ghantous, Noam Erez, Avital Bareket-Samish, Adva Levy-Barda, Haim Ben-Zvi, Neta Moskovits, Erez Bar-Haim (+1 others)
2021 medRxiv   pre-print
BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were
more » ... d using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.
doi:10.1101/2021.12.25.21268336 fatcat:d2fujinzvvcodokfzxxldua3om

The processing of dynamic faces in the human brain: Support for an integrated neural framework of face processing [article]

Michal Bernstein, Yaara Erez, Idan Blank, Galit Yovel
2017 bioRxiv   pre-print
Faces convey rich information including identity, gender and expression. Current neural models of face processing suggest a dissociation between the processing of invariant facial aspects such as identity and gender, that engage the fusiform face area (FFA) and the processing of changeable aspects, such as expression and eye gaze, that engage the posterior superior temporal sulcus face area (pSTS-FA). Recent studies report a second dissociation within this network such that the pSTS-FA, but not
more » ... the FFA, shows much stronger response to dynamic than static faces. The aim of the current study was to test a unified model that accounts for these two major functional characteristics of the neural face network. In an fMRI experiment, we presented static and dynamic faces while subjects judged an invariant (gender) or a changeable facial aspect (expression). We found that the pSTS-FA was more engaged in processing dynamic than static faces and changeable than invariant facial aspects, whereas the OFA and FFA showed similar response across all four conditions. Our results reveal no dissociation between the processing of changeable and invariant facial aspects, but higher sensitivity to the processing of changeable facial aspects by the motion-sensitive face area in the superior temporal sulcus.
doi:10.1101/140939 fatcat:guu72qnhfbflfg6ithkrg2h5qy

Bacterial gasdermins reveal an ancient mechanism of cell death [article]

Alex G Johnson, Tana Wein, Megan L Mayer, Brianna Duncan-Lowey, Erez Yirmiya, Yaara Oppenheimer-Shaanan, Gil Amitai, Rotem Sorek, Philip J Kranzusch
2021 bioRxiv   pre-print
Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. Here we discover gasdermin homologs encoded in bacteria that execute prokaryotic cell death. Structures of bacterial gasdermins reveal a conserved pore-forming domain that is stabilized in the inactive state with a buried
more » ... d modification. We demonstrate that bacterial gasdermins are activated by dedicated caspase-like proteases that catalyze site-specific cleavage and removal of an inhibitory C-terminal peptide. Release of autoinhibition induces the assembly of >200 Å pores that form a mesh-like structure and disrupt membrane integrity. These results demonstrate that caspase-mediated activation of gasdermins is an ancient form of regulated cell death shared between bacteria and animals.
doi:10.1101/2021.06.07.447441 fatcat:the3tpb56nf6njnzdegjgcv5wm

Dynamic reconfiguration of the default mode network during narrative comprehension

Erez Simony, Christopher J Honey, Janice Chen, Olga Lositsky, Yaara Yeshurun, Ami Wiesel, Uri Hasson
2016 Nature Communications  
Supplementary Figure 1 | ISFC filters out non-neuronal correlations. During both rest and task conditions, ISFC is unaffected by the three major non-neuronal sources of noise: heart rate 1,2 , respiration 1,3 and head motion 4 . Previous studies have shown that heart rate (HR) and slow changes in breathing depth and rate over time, known as the respiratory variation (RV), could account for significant variance in the gray matter signal during rest 5 . Here we measured the breathing and heart
more » ... e, and used the RVHRCORR model 1 to extract the low-frequency RV and HR during rest and while 9 subjects listened to the intact story (for details see Methods, "Low frequency respiratory and heart rate variation"). In agreement with previous reports, RV correlated with many brain areas within individuals during rest and during the story condition. (A) Cross-correlation (r~=0.5) between the RV and BOLD signal in the precuneus for one individual subject during rest. (B) The correlation between the RV and BOLD signal within the brain of an individual subject during rest is high. (C, D) The RV signals were uncorrelated across the 9 subjects during both the rest condition (r=-0.004, p>0.2) and the story condition (r=-0.02, p>0.18), validating our assumption that these non-neuronal artifacts can influence the FC analysis but not the ISFC analysis. Interestingly, by regressing out the RV signal from the precuneus timecourse and from early auditory areas (A1), we got a 20% increase in the intersubject correlation (ISC) in both areas. This suggests that by filtering out physiological noise for each subject during the preprocessing stage, we can better expose the stimulus-induced signal that is shared across subjects and revealed by the ISFC method. (E,F) Similarly, we found that the HR signals and head-motion trajectories were not correlated across subjects during rest (r< 0.04, p>0.26) or the story condition (r< 0.02, p>0.3). Together, these results provide empirical evidence for our hypothesis that the intrinsic neuronal signal and non-neuronal noise can induce high FC values within a brain, but no ISFC across subjects. This finding supports the ISFC equation in Figure 1D , where the ISFC correlation approaches zero in cases where I and N dominate the signal and 1 S and 2 S  are set to zero.
doi:10.1038/ncomms12141 pmid:27424918 pmcid:PMC4960303 fatcat:ye66i3jrerdqnhq7m4v4esc7ve

Assessment of neuropsychological function during early treatment of diffuse glioma [article]

Mallory Owen, Rafael Romero-Garcia, Alexa McDonald, Emma Woodberry, Pedro Coelho, Rob C Morris, Stephen J Price, Tom Santarius, John Suckling, Yaara Erez, Michael G Hart
2020 medRxiv   pre-print
Cognitive function in patients with diffuse glioma is frequently impaired and can have a profound impact on quality of life. Accurate, reproducible and accessible tools to assess cognition are mandatory to understand the effects of the tumour and treatment. Our hypothesis was that an app-based assessment would be complementary to traditional neuropsychological testing, thereby aiding in defining cognitive profiles and trajectories during early treatment of diffuse glioma. Methods: Seventeen
more » ... ects with diffuse low-grade gliomas completed a traditional neuropsychological assessment battery before and after surgery. In addition an app-based tablet assessment (OCS-Bridge) was administered pre- and post-operatively as well as longitudinally at 3- and 12-month follow-up. Deficit rates, mean performance, and changes over time were compared using standardized z-scores between the two testing methods. Unsupervised k-means clustering was performed on individual cognitive tests in each battery. Results: Preoperative testing showed an average of 2.88 deficits and 1.18 deficits per patient on neuropsychological testing and the tablet-based OCS-Bridge assessment, respectively. Digit span testing demonstrated agreement between testing modalities, but otherwise there was no significant correlation (Pearson's correlation: p=0.7723, r-value = 0.0758, df = 16). Longitudinal assessment revealed dynamic changes in attention and nonverbal skills. Traditional assessment was more sensitive to memory deficits, showing 22 preoperative deficits within the cohort vs. 1 for the app-based assessment, while app-based assessment was more sensitive to nonverbal skills, showing 8 deficits preoperatively vs. none in the traditional assessment. Clustering analysis did not create clusters along the predetermined domains, indicating that certain individual tests may test more than one cognitive function. Conclusions: These data suggest app-based assessment is reliable and complementary to data obtained from traditional neuropsychological testing. Advantages include efficiency, facilitation of longitudinal testing, and increased sensitivity in domains of non-verbal skills and attention. Patients with diffuse glioma show subtle neuropsychological impairments, unique cognitive profiles, and discrete trajectories during early treatment, therefore judicious assessment is imperative.
doi:10.1101/2020.06.03.20119255 fatcat:y6pyz4oevzgwtj5cpizdhybcfq

Brain network disruption predicts memory and attention deficits after surgical resection of glioma [article]

Rafael Romero-Garcia, Michael G Hart, Mallory Owen, Moataz Assem, Pedro Coelho, Alexa McDonald, Emma Woodberry, Stephen J Price, Amos GA Burke, Thomas Santarius, Yaara Erez, John Suckling
2019 medRxiv   pre-print
Surgical resection with adjuvant chemotherapy and radiotherapy are effective treatments to delay brain tumour progression and improve survival. Nevertheless, a large proportion of patients have treatment-induced cognitive deficits that dramatically reduce their life quality. A major problem in basic and clinical neuroscience is that the dispersed and interlocking nature of cognitive circuits makes predicting functional impairments challenging. Here we investigated tumour interactions with brain
more » ... networks in relation to cognitive recovery after surgical resection and during chemo-radiotherapy treatment. 17 patients with low- and high-grade glioma (aged 22-56 years) were longitudinally MRI-scanned and cognitively assessed using a tablet-based screening tool before and after surgery, and during a 12-months recovery period. Using structural MRI and Neurite Orientation Dispersion and Density Imaging (NODDI) derived from diffusion-weighted images, we respectively estimated tumour overlap and Neurite Density (as an in-vivo proxy measure of axon and dendrite concentration) with brain networks and functional maps derived from normative data in healthy participants. We found that neither total lesion volume nor tumour location based on traditional lobular divisions were associated with memory or attention deficits. However, tumour and lesion overlap with the Default Mode Network (DMN), Attention Network and attention-related regions located in frontal and parietal cortex was associated with memory and attention deficits. This association was above and beyond the contributions of preoperative cognitive status and tumour volume (Linear Mixed Model, Pfdr<0.05). On the other hand, Neurite Density derived was reduced not only within the tumour, but also beyond the tumour boundary, revealing a distal effect that can have global consequences on brain networks. High preoperative Neurite Density outside the tumour, but within the Frontoparietal Network was associated with better memory and attention recovery. Moreover, postoperative and follow-up Neurite Density within the DMN, Frontoparietal and Attention Networks was also associated with memory and attention improvements (Pfdr<0.05). We conclude that gliomas located on brain networks that are fundamental for cognitive processing mediate cognitive deficits in patients with brain tumours and that, despite being focal lesions, they exert a distal effect on Neurite Density in these networks that is also associated with cognitive recovery. Our work provides insights into the brain reorganisation that occurs due to the presence of a tumour and its potential capability to predict treatment-induced cognitive deficits. A better understanding of the impact of treatment on these brain circuits would contribute to designing multimodal biomarkers for enhancing patient stratification and tailored rehabilitation to better preserve cognitive function.
doi:10.1101/19008581 fatcat:wdqzett2hbgrhn4gmlznfnazcm

Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation

Anujan Poologaindran, Mike Hart, Tom Santarius, Stephen Price, Rohit Sinha, Mike Sughrue, Yaara Erez, Rafael Romero-Garcia, John Suckling
2021 Neuro-Oncology  
Aims Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the "mesoscale" architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following
more » ... ims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (&gt;1 year). Method With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, & 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories. Results Controlling for age and sex, the MD system's multi-scale architecture in health was positively associated with higher-order cognition (Catell's fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity. Conclusion This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.
doi:10.1093/neuonc/noab195.015 fatcat:7az6wjpwcbcdzkoos3plcn6sje

Progressive Recruitment of the Frontoparietal Multiple-demand System with Increased Task Complexity, Time Pressure, and Reward

Sneha Shashidhara, Daniel J. Mitchell, Yaara Erez, John Duncan
2019 Journal of Cognitive Neuroscience  
Yaara Erez was supported by a Royal Society Dorothy Hodgkin Research Fellowship, UK (DH130100).  ... 
doi:10.1162/jocn_a_01440 pmid:31274390 fatcat:5rrzd7fcczbe7ednxbos4h36le

Dispersed Activity during Passive Movement in the Globus Pallidus of the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Treated Primate

Yaara Erez, Hadass Tischler, Katya Belelovsky, Izhar Bar-Gad, Ted M. Dawson
2011 PLoS ONE  
Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons
more » ... from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease.
doi:10.1371/journal.pone.0016293 pmid:21267415 pmcid:PMC3022810 fatcat:fvxcawjpibc6zltmvlbspurozu
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