Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic functional connections determine how curiosity and prediction errors enhance memory

Individuals differ in the way they seek information, acquire knowledge, and form memories. Neural finger-prints of intrinsic functional connectivity distinguish between individuals and predict inter-individual differences in task performance. Both curiosity – the desire to acquire new information – and information prediction errors (IPEs) – the mismatch between information and previous expectations – enhance memory but differ considerably between individuals. The present study assessed whether inter-individual differences in functional connectivity measured using resting-state fMRI determine the extent to which individuals benefit from memory-enhancing effects of curiosity and IPEs. We found a double dissociation between individual differences in mesolimbic functional connectivity, which accounted for curiosity-driven but not IPE-related memory enhancements, and individual differences in cingulo-hippocampal functional connectivity, which predicted IPE-driven but not curiosity-related memory enhancements. These novel findings on how inter-individual differences in dissociable intrinsic functional networks determine memory enhancements stress the need to account for these differences in theoretical frameworks of curiosity and memory.
Intestinal transit amplifying cells require METTL3 for growth factor signaling, KRAS expression, and cell survival

Intestinal epithelial transit amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite their critical roles in intestinal homeostasis and disease, few studies have described genes that are essential to transit amplifying cell function. We report that the RNA methyltransferase, METTL3, is required for survival of transit amplifying cells in the murine small intestine. Transit amplifying cell death after METTL3 deletion was associated with crypt and villus atrophy, loss of absorptive enterocytes, and uniform wasting and death in METTL3-depleted mice. Ribosome profiling and sequencing of methylated RNAs in enteroids and in vivo demonstrated decreased translation of hundreds of unique methylated transcripts after METTL3 deletion, particularly transcripts involved in growth factor signal transduction such as Kras. Further investigation confirmed a novel relationship between METTL3 and Kras methylation and protein levels in vivo. Our study identifies METTL3 as an essential factor supporting the homeostasis of small intestinal tissue via direct maintenance of transit amplifying cell survival. We highlight the crucial role of RNA modifications in regulating growth factor signaling in the intestine, with important implications for both homeostatic tissue renewal and epithelial regeneration.
A core Nrf2 gene set defined through comprehensive transcriptomic analysis predicts drug resistance and poor multi-cancer prognosis

The NRF2-KEAP1 pathway plays an important role in the cellular response to oxidative stress but may also contribute to metabolic changes and drug resistance in cancer. We investigated the activation of NRF2 in human cancers and fibroblast cells through KEAP1 inhibition and cancer associated KEAP1/NRF2 mutations. We define a core set of 14 upregulated NRF2 target genes from seven RNA-Sequencing databases that we generated and analyzed, which we validated this gene set through analyses of published databases and gene sets. An NRF2 activity score based on expression of these core target genes correlates with resistance to drugs such as PX-12 and necrosulfonamide but not to paclitaxel or bardoxolone methyl. We validated these findings and also found NRF2 activation led to radioresistance in cancer cell lines. Finally, our NRF2 score is prognostic for cancer survival and validated in additional independent cohorts for novel cancers types not associated with NRF2-KEAP1 mutations. These analyses define a core NRF2 gene set that is robust, versatile, and useful as a NRF2 biomarker and for predicting drug resistance and cancer prognosis.
Isoform-specific translational control is evolutionarily conserved in primates

Alternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total cytosolic and polyribosome-associated mRNA from human, chimpanzee, and orangutan induced pluripotent stem cells (iPSCs), revealing thousands of transcripts with splicing differences between subcellular fractions. We found both conserved and species-specific polyribosome association patterns for orthologous splicing events. Intriguingly, alternative exons with similar polyribosome profiles between species have stronger sequence conservation than exons with lineage-specific ribosome association. These data suggest that sequence variation underlies differences in the polyribosome association. Accordingly, single nucleotide substitutions in luciferase reporters designed to model exons with divergent polyribosome profiles are sufficient to regulate translational efficiency. We used position specific weight matrixes to interpret exons with species-specific polyribosome association profiles, finding that polymorphic sites frequently alter recognition motifs for trans-acting RNA binding proteins. Together, our results show that AS can regulate translation by remodeling the cis-regulatory landscape of mRNA isoforms.
Mutualism at the leading edge: Insights into the eco-evolutionary dynamics of host-symbiont communities during range expansion

The evolution of mutualism between host and symbiont communities plays an essential role in maintaining ecosystem function and should therefore have a pro-found effect on their range expansion dynamics. In particular, the presence of mutualistic symbionts at the leading edge of a host-symbiont community should enhance its propagation in space. We develop a theoretical framework that captures the eco-evolutionary dynamics of host-symbiont communities, to investigate how the evolution of resource exchange may shape community structure during range expansion. We consider a community with symbionts that are mutualistic or parasitic to various degrees, where parasitic symbionts receive the same amount of resource from the host as mutualistic symbionts, but at lower cost. The selective advantage of parasitic symbionts over mutualistic ones is strengthened with resource availability (i.e. with host density), promoting mutualism at the range edges, where host density is low, and parasitism in the population core, where host density is higher. This spatial selection also influences the speed of spread. We find that the host growth rate (which depends on the average benefit provided by the symbionts) is maximal at the range edges, where symbionts are more mutualistic, and that host-symbiont communities with high symbiont density at their core (e.g. resulting from more mutualistic hosts) spread faster into new territories. These results indicate that the expansion of host-symbiont communities is pulled by the hosts but pushed by the symbionts, in a unique push-pull dynamic where both the host and symbionts are active and tightly-linked players.
Public participation in marine spatial planning in Iceland

Introduction Marine Spatial Planning (MSP) aims at ecosystem-based management of ocean resources that brings different stakeholders and the public together to discuss their conflicts of interest and forge a sustainable path forward. Public participation is a crucial element of MSP to make it democratically legitimate and sustainable in the long-term. MSP was formally introduced by law in Iceland in 2018 and two projects were initiated in the Westfjords and Eastfjords in 2019, with one further planned in Skjálfandi Bay. Methods To assess the scope and depth of public participation in those MSP projects, data was collected through semi-structured interviews (n=80), conversations, observations and document analysis during the data gathering and proposal stages of the planning processes. Results The results show that a limited group of people including institutional actors and formal stakeholders had been engaged in the information gathering stages of the process, but in the later phases of decision-making, local community members were notably absent. Discussion/Conclusion This lack of public participation highlights the need for more in-depth communication about the MSP process and marine issues in the adjacent communities as well as an urgent need for inclusion of the public into marine decision-making and MSP.
Mirror-terminated Mach-Zehnder interferometer based on SiNOI slot and strip waveguides for sensing applications using visible light

In this work, a highly sensitive sensor based on silicon nitride (SiN) waveguide is proposed that can be used for gas sensing using visible light. The whole sensor waveguide uses a silicon dioxide (SiO2) cladding while the sensing arm uses a fluidic cladding such as water. The proposed device is based on loop-mirror terminated (LMT) Mach-Zehnder interferometer (MZI), where the reference arm is exposed to the reference SiO2 medium, while the sensing arm is exposed to the sensing medium leading to a change in the refractive index of the waveguide cladding. The sensor performance is overall optimized by optimizing the design performance of all the components of the structure one by one. The waveguide sensitivity of both strip and slot types is analyzed for gaseous medium in order to compare their sensitivities and select the dimensions of the waveguide that results in the highest device sensitivity. Transverse-electric (TE) polarization is considered in this study for strip waveguide, where a higher sensitivity is founded with respect to the transverse-magnetic (TM) polarization. The field confinement in the slot waveguide in the sensing region is investigated and verified with a mode solver, where the optimum dimensions are obtained using finite difference eigenmode and finite difference time domain solvers. With a sensing arm length of 150 μm only, the proposed sensor achieves a device sensitivity of about 1,320 nm/RIU and a figure-of-merit (FOM) as high as 641 RIU−1 at the wavelength of 650 nm, which is the highest reported FOM up to the author’s knowledge. Higher values of the FOM are possible by employing a longer sensing arm.
A cost analysis of robotic vs. video-assisted thoracic surgery: The impact of the learning curve and the COVID-19 pandemic

Introduction Robot-assisted thoracoscopic surgery (RATS) is an alternative to video-assessed thoracoscopic surgery (VATS) for the treatment of lung cancer but concern exists regarding the high associated costs. The COVID-19 pandemic added further financial pressure to healthcare systems. This study investigated the impact of the learning curve on the cost-effectiveness of RATS lung resection and the financial impact of the COVID-19 pandemic on a RATS program. Methods Patients undergoing RATS lung resection between January 2017 and December 2020 were prospectively followed. A matched cohort of VATS cases were analyzed in parallel. The first 100 and most recent 100 RATS cases performed at our institution were compared to assess the learning curve. Cases performed before and after March 2020 were compared to assess the impact of the COVID-19 pandemic. A comprehensive cost analysis of multiple theatre and postoperative data points was performed using Stata statistics package (v14.2). Results 365 RATS cases were included. Median cost per procedure was £7,167 and theatre cost accounted for 70%. Major contributing factors to overall cost were operative time and postoperative length of stay. Cost per case was £640 less after passing the learning curve (p < 0.001) largely due to reduced operative time. Comparison of a post-learning curve RATS subgroup matched to 101 VATS cases revealed no significant difference in theatre costs between the two techniques. Overall cost of RATS lung resections performed before and during the COVID-19 pandemic were not significantly different. However, theatre costs were significantly cheaper (£620/case; p < 0.001) and postoperative costs were significantly more expensive (£1,221/case; p = 0.018) during the pandemic. Discussion Passing the learning curve is associated with a significant reduction in the theatre costs associated with RATS lung resection and is comparable with the cost of VATS. This study may underestimate the true cost benefit of passing the learning curve due to the effect of the COVID-19 pandemic on theatre costs. The COVID-19 pandemic made RATS lung resection more expensive due to prolonged hospital stay and increased readmission rate. The present study offers some evidence that the initial increased costs associated with RATS lung resection may be gradually offset as a program progresses.
A remote sensing based method for assessing the impact of O3 on the net primary productivity of terrestrial ecosystems in China

O3 pollution in China has been increasing in recent years, but the process of O3 impact on net primary productivity of terrestrial ecosystems remains unclear. We attempts to explore a remote sensing-based method to assess the impact of O3 on NPP of China’s terrestrial ecosystems by combining MODIS NPP and the latest ground observation data of O3 concentration. By comparing the NPP data of MODIS image pixels with the 6-year average AOT40 data of corresponding pixels, we extracted the signal data that highlighted the effects of O3 on NPP and established the response relationships between AOT40 and NPP. It was found that NPP was significantly negatively correlated with AOT40 in farmland and grassland ecosystems in China (farmland: r = 0.8674, p < 0.003, grassland: r = 0.7181, p < 0.03). Then the response relationships were adopted to evaluate the effect in China in 2014. The results showed that the estimated percentage of O3-induced NPP decline was in the range of 5%–35%. Among them, the most significant declines were found in farmland ecosystems, with the vast majority of declines in 10%–35%. The decrease rate of evergreen coniferous forests ranked second, mostly in the range of 15%–20%. The grassland ecosystems declined at a lower rate, almost between 5% and 15%. And the evergreen broad-leaved forests has the lowest decline rate, most distributed in 0%–5%. The highest percentage decreases were mainly found in the Beijing-Tianjin-Hebei region and Shandong Province. And the decline rate of farmland ecosystems was significantly higher than other ecosystem types.
Simulation test for impartment of use-dependent plasticity by inactivation of axonal potassium channels on hippocampal mossy fibers

Modification of axonal excitability directly impacts information transfer through the neuronal networks in the brain. However, the functional significance of modulation of axonal excitability by the preceding neuronal activity largely remains elusive. One remarkable exception is the activity-dependent broadening of action potential (AP) propagating along the hippocampal mossy fibers. The duration of AP is progressively prolonged during repetitive stimuli and facilitated presynaptic Ca2+ entry and subsequent transmitter release. As an underlying mechanism, accumulated inactivation of axonal K+ channels during AP train has been postulated. As the inactivation of axonal K+ channels proceeds on a timescale of several tens of milliseconds slower than the millisecond scale of AP, the contribution of K+ channel inactivation in AP broadening needs to be tested and evaluated quantitatively. Using the computer simulation approach, this study aimed to explore the effects of the removal of the inactivation process of axonal K+ channels in the simple but sufficiently realistic model of hippocampal mossy fibers and found that the use-dependent AP broadening was completely abolished in the model replaced with non-inactivating K+ channels. The results demonstrated the critical roles of K+ channel inactivation in the activity-dependent regulation of axonal excitability during repetitive action potentials, which critically imparts additional mechanisms for robust use-dependent short-term plasticity characteristics for this particular synapse.
Depression and anxiety among Macau residents during the COVID-19 outbreak: A network analysis perspective

Background The 2019 novel coronavirus disease (COVID-19) outbreak affected people’s lifestyles and increased their risk for depressive and anxiety symptoms (depression and anxiety, respectively hereafter). We assessed depression and anxiety in residents of Macau during “the 6.18 COVID-19 outbreak” period and explored inter-connections of different symptoms from the perspective of network analysis. Methods In this cross-sectional study, 1,008 Macau residents completed an online survey comprising the nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalized Anxiety Disorder Scale (GAD-7) to measure depression and anxiety, respectively. Central and bridge symptoms of the depression-anxiety network model were evaluated based on Expected Influence (EI) statistics, while a bootstrap procedure was used to test the stability and accuracy of the network model. Results Descriptive analyses indicated the prevalence of depression was 62.5% [95% confidence interval (CI) = 59.47–65.44%], the prevalence of anxiety was 50.2% [95%CI = 47.12–53.28%], and 45.1% [95%CI = 42.09–48.22%] of participants experienced comorbid depression and anxiety. “Nervousness-Uncontrollable worry” (GADC) (EI = 1.15), “Irritability” (GAD6) (EI = 1.03), and “Excessive worry” (GAD3) (EI = 1.02) were the most central symptoms, while “Irritability” (GAD6) (bridge EI = 0.43), “restlessness” (GAD5) (bridge EI = 0.35), and “Sad Mood” (PHQ2) (bridge EI = 0.30) were key bridge symptoms that emerged in the network model. Conclusion Nearly half of residents in Macau experienced comorbid depression and anxiety during the 6.18 COVID-19 outbreak. Central and bridge symptoms identified in this network analysis are plausible, specific targets for treatment and prevention of comorbid depression and anxiety related to this outbreak.
Endovascular thrombectomy is cost-effective in acute basilar artery occlusion stroke

Objective Endovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness. Methods A Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product per capita, as recommended by the World Health Organization. Results Endovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure. Conclusion Endovascular treatment is cost-effective in patients with aBAO stroke.
We like to move it, move it: A perspective on performing passive leg movement as a non-invasive assessment of vascular function in pediatric populations

The passive leg movement (PLM) technique is a non-invasive assessment of lower-limb vascular function. PLM is methodologically simple to perform and utilizes Doppler ultrasound to determine leg blood flow (LBF) through the common femoral artery at rest and in response to passive movement of the lower leg. LBF responses to PLM have been reported to be mostly nitric oxide (NO)-mediated when performed in young adults. Moreover, PLM-induced LBF responses, as well as the NO contribution to PLM-induced LBF responses, are reduced with age and in various diseased populations, demonstrating the clinical utility of this non-invasive test. However, no PLM studies to date have included children or adolescents. Since its conception in 2015, our laboratory has performed PLM on hundreds of individuals including a large cohort of children and adolescents. Thus, the purpose of this perspective article is threefold: 1) to uniquely discuss the feasibility of performing PLM in children and adolescents, 2) to report PLM-induced LBF values from our laboratory in 7–17-year-olds, and 3) to discuss considerations for making comparisons among pediatric populations. Based on our experiences performing PLM in children and adolescents (among various other age groups), it is our perspective that PLM can feasibly be performed in this population. Further, data from our laboratory may be used to provide context for typical PLM-induced LBF values that could be observed in children and adolescents, as well as across the lifespan.
Conservation and divergence of expression of GA2-oxidase homeologs in apple (Malus x domestica Borkh.)

In domesticated apple (Malus x domestica Borkh.) and other woody perennials, floral initiation can be repressed by gibberellins (GAs). The associated mechanism is a major unanswered question in plant physiology, and understanding organismal aspects of GA signaling in apple has important commercial applications. In plants, the major mechanism for elimination of GAs and resetting of GA signaling is through catabolism by GA2-oxidases (GA2ox). We found that the GA2ox gene family in apple comprises 16 genes representing eight, clearly defined homeologous pairs, which were named as MdGA2ox1A/1B to MdGA2ox8A/8B. Expression of the genes was analyzed in the various structures of the spur, where flowers are initiated, as well as in various structures of seedlings over one diurnal cycle and in response to water-deficit and salt stress. Among the results, we found that MdGA2ox2A/2B dominated expression in the shoot apex and were strongly upregulated in the apex after treatment with exogenous GA3, suggesting potential involvement in repression of flowering. Several MdGA2ox genes also showed preferential expression in the leaf petiole, fruit pedicel, and the seed coat of developing seeds, potentially representing mechanisms to limit diffusion of GAs across these structures. In all contexts studied, we documented both concerted and distinct expression of individual homeologs. This work introduces an accessible woody plant model for studies of GA signaling, GA2ox gene regulation, and conservation/divergence of expression of homeologous genes, and should find application in development of new cultivars of apple and other tree fruits.