Miracle-dz/UniFAR-FTUs huggingface dataset:
Storage of carbon reserves in spruce trees is prioritized over growth in the face of carbon limitation

Significance Forest decline due to climate change is increasing worldwide. Accurate forecasting of forest dynamics requires a mechanistic understanding of carbon allocation strategies that can link molecular process regulation to whole-tree responses. However, dedicated transdisciplinary investigations spanning these scales are lacking. Here we used a unique experimental platform to manipulate the whole-tree carbon balance and combine metabolic flux measurements with transcriptional information to reveal tree resource allocation priorities under reduced carbon supply. In contrast to current understanding and model implementations, we show that trees prioritize carbon allocation to storage and mobilization of storage to support respiration rather than growth to ensure immediate and future survival under negative carbon balance that may occur during critical periods of stress. Climate change is expected to pose a global threat to forest health by intensifying extreme events like drought and insect attacks. Carbon allocation is a fundamental process that determines the adaptive responses of long-lived late-maturing organisms like trees to such stresses. However, our mechanistic understanding of how trees coordinate and set allocation priorities among different sinks (e.g., growth and storage) under severe source limitation remains limited. Using flux measurements, isotopic tracing, targeted metabolomics, and transcriptomics, we investigated how limitation of source supply influences sink activity, particularly growth and carbon storage, and their relative regulation in Norway spruce (Picea abies) clones. During photosynthetic deprivation, absolute rates of respiration, growth, and allocation to storage all decline. When trees approach neutral carbon balance, i.e., daytime net carbon gain equals nighttime carbon loss, genes encoding major enzymes of metabolic pathways remain relatively unaffected. However, under negative carbon balance, photosynthesis and growth are down-regulated while sucrose and starch biosynthesis pathways are up-regulated, indicating that trees prioritize carbon allocation to storage over growth. Moreover, trees under negative carbon balance actively increase the turnover rate of starch, lipids, and amino acids, most likely to support respiration and mitigate stress. Our study provides molecular evidence that trees faced with severe photosynthetic limitation strategically regulate storage allocation and consumption at the expense of growth. Understanding such allocation strategies is crucial for predicting how trees may respond to extreme events involving steep declines in photosynthesis, like severe drought, or defoliation by heat waves, late frost, or insect attack.
Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

AIMS The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion. CONCLUSIONS The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.
Fears about COVID‐19 and perceived risk among people with rheumatoid arthritis or ankylosing spondylitis following the initial lockdown in Aotearoa New Zealand

Abstract Background The COVID‐19 pandemic has disrupted all aspects of life and may raise particular fears for people with rheumatic disease. There is a need for research on fears and perceived risk of SARS‐CoV‐2 so as to understand the impact on wellbeing and inform service provision. Objectives The aim of this study was to examine the correlates of COVID‐19 fears and perceived risk of SARS‐CoV‐2 among people with rheumatoid arthritis or ankylosing spondylitis. Design A cross‐sectional survey design was applied in Aotearoa New Zealand in the period after initial nationwide lockdowns. Method An online survey was completed from July to September 2020 by 126 individuals with rheumatoid arthritis (n = 96) or ankylosing spondylitis (n = 30) who had previously been recruited to the Patient Opinion Real‐Time Anonymous Liaison (PORTAL) study in 2015 or 2018. The survey included demographics and health information as well as measures of COVID‐19 fears and experiences, functional disability and fatigue‐related disability. Results Fears about COVID‐19 were higher among younger participants, those who had been tested for SARS‐CoV‐2, and those who experienced more flares over the initial lockdown. Perceived risk of SARS‐CoV‐2 infection was also higher among individual who had been tested for SARS‐CoV‐2 and those taking biologic medications. Conclusion Fears about COVID‐19 and perceived risk of infection are related to age, health and medications among individuals with rheumatoid arthritis or ankylosing spondylitis. These findings inform how health professionals can help address the concerns of particular groups of people with rheumatic disease by providing relevant information about the ongoing effects of the pandemic.
A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation

Wang et al provide insight into how epigenetic regulation of the transcriptome can rewire cell fate decisions by mapping the RNA-editing landscape during hematopoiesis. They report that adenosine-to-inosine RNA editing of antizyme inhibitor 1 (Azin1) is a novel regulator of hematopoietic cell fate, capable of influencing self-renewal and differentiation of hematopoietic stem cells. This work sets the scene for developing RNA editing–targeted therapeutics for stem cell expansion and modulating AZIN1-induced cancer stem cell generation.
Highly Accurate Real-Time Decomposition of Single Channel Intramuscular EMG

Objective: Real-time intramuscular electromyography (iEMG) decomposition, as an identification procedure of individual motor neuron (MN) discharge timings from a streaming iEMG recording, has the potential to be used in human-machine interfacing. However, for these applications, the decomposition accuracy and speed of current approaches need to be improved. Methods: In our previous work, a real-time decomposition algorithm based on a Hidden Markov Model of EMG, using GPU-implemented Bayesian filter to estimate the spike trains of motor units (MU) and their action potentials (MUAPs), was proposed. In this paper, a substantially extended version of this algorithm that boosts the accuracy while maintaining real-time implementation, is introduced. Specifically, multiple heuristics that aim at resolving the problems leading to performance degradation, are applied to the original model. In addition, the recursive maximum likelihood (RML) estimator previously used to estimate the statistical parameters of the spike trains, is replaced by a linear regression (LR) estimator, which is computationally more efficient, in order to ensure real-time decomposition with the new heuristics. Results: The algorithm was validated using twenty-one experimental iEMG signals acquired from the tibialis anterior muscle of five subjects by fine wire electrodes. All signals were decomposed in real time. The decomposition accuracy depended on the level of muscle activation and was $>90\%$ when less than 10 MUs were identified, substantially exceeding previous real-time results. Conclusion: Single channel iEMG signals can be very accurately decomposed in real time with the proposed algorithm. Significance: The proposed highly accurate algorithm for single-channel iEMG decomposition has the potential of providing neural information on motor tasks for human interfacing.
Hierarchical self-assembly of polydisperse colloidal bananas into a two-dimensional vortex phase

Significance Hierarchically self-assembled materials—structures with order at multiple length scales—can be found everywhere. Examples range from collagen structures in human bones to engineered photonic materials. These structures usually assemble from monodisperse microscopic building blocks that interact via complex directional interactions. In this work, we show that hierarchical materials can, in fact, also be assembled from polydisperse building blocks and by entropic interactions alone. Our simple yet powerful assembly mechanism opens up avenues toward rationally exploiting the often undesired polydispersity of colloidal building blocks for programming entropy-driven self-assembly of hierarchical materials. Self-assembly of microscopic building blocks into highly ordered and functional structures is ubiquitous in nature and found at all length scales. Hierarchical structures formed by colloidal building blocks are typically assembled from monodisperse particles interacting via engineered directional interactions. Here, we show that polydisperse colloidal bananas self-assemble into a complex and hierarchical quasi–two-dimensional structure, called the vortex phase, only due to excluded volume interactions and polydispersity in the particle curvature. Using confocal microscopy, we uncover the remarkable formation mechanism of the vortex phase and characterize its exotic structure and dynamics at the single-particle level. These results demonstrate that hierarchical self-assembly of complex materials can be solely driven by entropy and shape polydispersity of the constituting particles.
Evolutionary perspectives on African North American genetic diversity: Origins and prospects for future investigations

African‐descended peoples of the Americas represent an amalgamation of West, Central, and Southeast African regional and ethnic groups with modest gene flow from specific non‐African populations. Despite 16+ generations of residence in the Americas, there is a deficit of evolutionary knowledge about these populations. Focusing on Legacy African American, the African North American descendants of survivors of the transatlantic trade in enslaved Africans, we report on emic evolutionary perspectives of their self‐identity gleaned from our interviews of 600 individuals collected over 2 years. Gullah‐Geechee peoples of Carolina Coastal regions are a model case study due to their historical antiquity, substantial African retentions, relative geospatial isolation, and proposed progenitor status to other Legacy African American microethnic groups. We identify salient research questions for future studies that will begin to bridge the evolutionary gaps in our knowledge of these diverse peoples and the historical evidence for specific evolutionary processes.
Ecology drives the evolution of diverse social strategies in Pseudomonas aeruginosa

Bacteria often cooperate by secreting molecules that can be shared as public goods between cells. Because the production of public goods is subject to cheating by mutants that exploit the good without contributing to it, there has been great interest in elucidating the evolutionary forces that maintain cooperation. However, little is known about how bacterial cooperation evolves under conditions where cheating is unlikely to be of importance. Here we use experimental evolution to follow changes in the production of a model public good, the iron‐scavenging siderophore pyoverdine, of the bacterium Pseudomonas aeruginosa. After 1200 generations of evolution in nine different environments, we observed that cheaters only reached high frequency in liquid medium with low iron availability. Conversely, when adding iron to reduce the cost of producing pyoverdine, we observed selection for pyoverdine hyperproducers. Similarly, hyperproducers also spread in populations evolved in highly viscous media, where relatedness between interacting individuals is increased. Whole‐genome sequencing of evolved clones revealed that hyperproduction is associated with mutations involving genes encoding quorum‐sensing communication systems, while cheater clones had mutations in the iron‐starvation sigma factor or in pyoverdine biosynthesis genes. Our findings demonstrate that bacterial social traits can evolve rapidly in divergent directions, with particularly strong selection for increased levels of cooperation occurring in environments where individual dispersal is reduced, as predicted by social evolution theory. Moreover, we establish a regulatory link between pyoverdine production and quorum‐sensing, showing that increased cooperation with respect to one trait (pyoverdine) can be associated with the loss (quorum‐sensing) of another social trait.
ProFit‐1D—A 1D fitting software and open‐source validation data sets

Accurate and precise MRS fitting is crucial for metabolite concentration quantification of 1H‐MRS spectra. LCModel, a spectral fitting software, has shown to have certain limitations to perform advanced spectral fitting by previous literature. Herein, we propose an open‐source spectral fitting algorithm with adaptive spectral baseline determination and more complex cost functions.
From clinical trials to clinical practice: How long are drugs tested and then used by patients?

Abstract Objective Evidence is scarce regarding the safety of long-term drug use, especially for drugs treating chronic diseases. To bridge this knowledge gap, this research investigated the differences in drug exposure between clinical trials and clinical practice. Materials and Methods We extracted drug follow-up times from clinical trials in ClinicalTrials.gov and compared the difference between clinical trials and real-world usage data for 914 drugs taken by 96 645 927 patients. Results A total of 17.5% of drugs had longer median exposure in practice than in trials, 6% of patients had extended exposure to at least 1 drug, and drugs treating nervous system disorders and cardiovascular diseases were the most common among drugs with high rates of extended exposure. Conclusions For most of patients, the drug use length is shorter than the tested length in clinical trials. Still, a remarkable number of patients experienced extended drug exposure, particularly for drugs treating nervous system disorders or cardiovascular disorders.
Re‐calibrating pure risk integrating individual data from two‐phase studies with external summary statistics

Accurate risk assessment is critical in clinical decision‐making. It entails the projected risk based on a risk prediction model agreeing with the observed risk in the target cohort. However, the model often over‐ or under‐estimates the risk. Building a new model for the target cohort would be ideal but costly. It is therefore of great interest to recalibrate an existing model for the target cohort. Existing methods have been proposed to recalibrate the model by leveraging the disease incidence rates from the target cohort. However, they assume the same covariate distribution across cohorts and when the assumption is violated, the recalibrated model can be substantially biased. Further, recalibration is also complicated by the two‐phase sampling design that is commonly used for developing risk prediction models. In this paper, we develop a weighted estimating‐equation approach accounting for the two‐phase design and combine it with a weighted empirical likelihood that leverages the summary information on both disease incidence rates and covariates from the target cohort. We provide a resampling‐based inference procedure. Our extensive simulation results show that using the summary information from the target population, the proposed recalibration method yields nearly unbiased risk estimates under a wide range of scenarios. An application to a colorectal cancer study also illustrates that the proposed method yields a well‐calibrated model in the target cohort.
Tear Neuromediator and Corneal Denervation Following SMILE.

PURPOSE To investigate the changes in tear neuromediators and corneal subbasal nerve plexus following small incision lenticule extraction (SMILE) and to study its association with different refractive power of corrections. METHODS Thirty patients were included for tear neuromediator analysis (40 eyes) and corneal nerve analysis using in vivo confocal microscopy scans (20 eyes). Tear samples were collected preoperatively and 1 week and 1, 3, 6, and 12 months postoperatively and analyzed for the substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) concentrations using the enzyme-linked immunosor-bent assay (ELISA). RESULTS Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) decreased significantly postoperatively, then gradually increased from 3 months onward, but did not recover to the baseline levels at 12 months. Tear substance P and CGRP levels remained stable over 12 months. Tear NGF levels demonstrated a small peak at 1 week before decreasing significantly compared to preoperative levels at 6 months (P = .03) and 12 months (P = .007). The 1-month reduction in CNFL, tear substance P, and CGRP concentrations were significantly correlated with the corrected spherical equivalent (SE) (r = 0.71 for CNFL; r = -0.33 to -0.52 at different time points for substance P and CGRP, respectively, all P < .05). Compared to the low to moderate myopia group, the high myopia group (corrected SE greater than -6.00 diopters) had a significantly greater decrease in CNFD, significantly higher tear substance P concentrations at 1 week, 1 month, and 6 months, and significantly higher tear CGRP concentrations at 1 and 6 months. CONCLUSIONS These results provide new insight into the neurobiological responses and their potential implications in corneal nerve damage and recovery after SMILE. High myopia treatment was associated with greater corneal denervation and neuroinflammation. [J Refract Surg. 2021;37(8):516-523. ].
Cell-Intrinsic Mechanisms of Drug Tolerance to Systemic Therapies in Cancer

In patients with cancer with metastatic disease, the rate of complete tumor response to systemic therapies is low, and residual lesions persist in the majority of patients due to early molecular adaptation in cancer cells. A growing body of evidence suggests that a subpopulation of drug-tolerant persister cells—a reversible phenotype characterized by reduced drug sensitivity and decreased cell proliferation—maintains residual disease and may serve as a reservoir for resistant phenotypes. The survival of these residual tumor cells can be caused by reactivation of specific signaling pathways, phenotypic plasticity (i.e., transdifferentiation), epigenetic or metabolic reprogramming, downregulation of apoptosis as well as transcriptional remodeling. In this review, we discuss the molecular mechanisms that enable adaptive survival in drug-tolerant cells. We describe the main characteristics and dynamic nature of this persistent state, and highlight the current therapeutic strategies that may be used to interfere with the establishment of drug-tolerant cells, as an alternative to improve objective response to systemic therapies and delay the emergence of resistance to improve long-term survival.
Metal-organic Frameworks as Novel Adsorbents: A Preview

Adsorption processes are among the most patronized applications of Metal-Organic Frameworks. Through adsorption MOFs have found usefulness in diverse sectors of human endeavors such as; removal of noxious and harmful substances (dyes and heavy metals from liquid/gaseous media discharged from industries), storage and sequestration of gases (carbon dioxide, methane and hydrogen), separation and purification of gases/petroleum products, catalytic processes and drug delivery. Functionalized MOFs can indeed show spectacular effects owing to the introduction of more active functional groups. Therefore, the performance and applicability of MOFs as sorbents in industrial processes depends on the degree of introduced functionality, high surface area and enhanced porosity.
A physical model of mantis shrimp for exploring the dynamics of ultrafast systems

Significance Many small organisms produce ultrafast movements by storing elastic energy and mediating its storage and rapid release through a latching mechanism. The mantis shrimp in particular imparts extreme accelerations on rotating appendages to strike their prey. Biologists have hypothesized, but not tested, that there exists a geometric latching mechanism which mediates the actuation of the appendage. Inspired by the anatomy of the mantis shrimp striking appendage, we develop a centimeter-scale robot which emulates the linkage dynamics in the mantis shrimp and study how the underlying geometric latch is able to control rapid striking motions. Our physical and analytical models could also be extended to other behaviors such as throwing or jumping in which high power over short duration is required. Efficient and effective generation of high-acceleration movement in biology requires a process to control energy flow and amplify mechanical power from power density–limited muscle. Until recently, this ability was exclusive to ultrafast, small organisms, and this process was largely ascribed to the high mechanical power density of small elastic recoil mechanisms. In several ultrafast organisms, linkages suddenly initiate rotation when they overcenter and reverse torque; this process mediates the release of stored elastic energy and enhances the mechanical power output of extremely fast, spring-actuated systems. Here we report the discovery of linkage dynamics and geometric latching that reveals how organisms and synthetic systems generate extremely high-acceleration, short-duration movements. Through synergistic analyses of mantis shrimp strikes, a synthetic mantis shrimp robot, and a dynamic mathematical model, we discover that linkages can exhibit distinct dynamic phases that control energy transfer from stored elastic energy to ultrafast movement. These design principles are embodied in a 1.5-g mantis shrimp scale mechanism capable of striking velocities over 26 m s−1 in air and 5 m s−1 in water. The physical, mathematical, and biological datasets establish latching mechanics with four temporal phases and identify a nondimensional performance metric to analyze potential energy transfer. These temporal phases enable control of an extreme cascade of mechanical power amplification. Linkage dynamics and temporal phase characteristics are easily adjusted through linkage design in robotic and mathematical systems and provide a framework to understand the function of linkages and latches in biological systems.