Miracle-dz/UniFAR-FTUs huggingface dataset:
Action planning and control under uncertainty emerge through a desirability-driven competition between parallel encoding motor plans

Living in an uncertain world, nearly all of our decisions are made with some degree of uncertainty about the consequences of actions selected. Although a significant progress has been made in understanding how the sensorimotor system incorporates uncertainty into the decision-making process, the preponderance of studies focus on tasks in which selection and action are two separate processes. First people select among alternative options and then initiate an action to implement the choice. However, we often make decisions during ongoing actions in which the value and availability of the alternatives can change with time and previous actions. The current study aims to decipher how the brain deals with uncertainty in decisions that evolve while acting. To address this question, we trained individuals to perform rapid reaching movements towards two potential targets, where the true target location was revealed only after the movement initiation. We found that reaction time and initial approach direction are correlated, where initial movements towards intermediate locations have longer reaction times than movements that aim directly to the target locations. Interestingly, the association between reaction time and approach direction was independent of the target probability. By modeling the task within a recently proposed neurodynamical framework, we showed that action planning and control under uncertainty emerge through a desirability-driven competition between motor plans that are encoded in parallel.
A longitudinal study of cognition, functional outcome and quality of life in bipolar disorder and major depression

Abstract Objective Cognitive impairments are known to be a frequent cause of disability in bipolar disorder (BD) and major depression (MDD). Yet there is no consensus regarding the particular cognitive functions whose impairments can lead to disability in each domain of functioning. The aim of this study was to perform a longitudinal evaluation of working memory, inhibition, cognitive flexibility and attention in BD and MDD, investigate the relationship of these cognitive functions to disability and quality of life, and evaluate the impact of variables related to cognitive reserve (education and daily cognitive stimulation) on cognitive performance. Method 31 participants (MDD = 12; BD = 19) were evaluated at baseline and after an average time of 2 years. Results the BD group showed improvements in attention while patients with MDD improved on measures of attention and working memory. In BD working memory performance was associated with the cognition and mobility domains of functioning, and with physical and environmental quality of life. In MDD, cognitive flexibility was related to social relationships and environmental quality of life. Conclusion working memory and cognitive flexibility may be an interesting target for interventions aiming to improve everyday functioning and quality of life in BD and MDD.
Superconducting Phase Induced by a Local Structure Transition in Amorphous Sb_{2}Se_{3} under High Pressure.

Superconductivity and Anderson localization represent two extreme cases of electronic behavior in solids. Surprisingly, these two competing scenarios can occur in the same quantum system, e.g., in an amorphous superconductor. Although the disorder-driven quantum phase transition has attracted much attention, its structural origins remain elusive. Here, we discovered an unambiguous correlation between superconductivity and density in amorphous Sb_{2}Se_{3} at high pressure. Superconductivity first emerges in the high-density amorphous (HDA) phase at about 24 GPa, where the density of glass unexpectedly exceeds its crystalline counterpart, and then shows an enhanced critical temperature when pressure induces crystallization at 51 GPa. Ab initio simulations reveal that the bcc-like local geometry motifs form in the HDA phase, arising from distinct "metavalent bonds. " Our results demonstrate that HDA phase is critical for the incipient superconductive behavior.
Disentangling the effects of male age and mating history: Contrasting effects of mating history on precopulatory mating behavior and paternity success

Many studies ask whether young or older males are better at acquiring mates. Even so, how age affects reproductive success is still poorly understood because male age and mating history are confounded in most studies: older males usually have more mating experience. To what extent does mating history rather than age explain variation in male mating success? And how do mating history and male age determine paternity when there is also postcopulatory sexual selection? Here, we experimentally manipulated the mating history of old and young males in the eastern mosquitofish (Gambusia holbrooki). We then recorded male mating behavior and share of paternity (1259 offspring from 232 potential sires) when they competed for mates and fertilizations. Old males, and males with no mating experience, spent significantly more time approaching females, and attempting to mate, than did young males and those with greater mating experience. Male age and mating history interacted to affect paternity: old males benefited from having previous mating experience, but young males did not. Our results highlight that the age‐related changes in male reproductive traits and in paternity that have been described in many taxa may be partly attributable to male mating history and not simply to age itself.
Immune checkpoint blockade sensitivity and progression-free survival associates with baseline CD8+ T cell clone size and cytotoxicity

Description The cytotoxicity and clone size of CD8+ T cell pretreatment are prognostic for immune checkpoint blockade. Baseline killers aid immune checkpoint blockade CD8+ T cells are crucial for the efficacy of immune checkpoint blockades (ICB), but it is unclear how specific T cell subsets or clones affect efficacy. Here, Watson et al. used transcriptomic approaches to phenotype the subsets and TCR clones of peripheral CD8+ T cells in eight patients with metastatic melanoma before and during ICB. They found that many of the expanded T cell clones during ICB were from a pool of cytotoxic T cell clones present pretreatment. In a larger independent clinical dataset of patients with melanoma, the authors found that the clone size and cytotoxicity of CD8+ T cells before treatment positively correlated to ICB efficacy. Together, these data suggest that targeting preexisting cytotoxic CD8+ T cell clones might improve the antitumor responses of ICB. The antitumor action of immune checkpoint blockade (ICB) is primarily mediated by CD8+ T cells. How sensitivity to ICB varies across CD8+ T cell subsets and clonotypes and the relationship of these with clinical outcome is unclear. To explore this, we used single-cell V(D)J and RNA-sequencing to track gene expression changes elicited by ICB across individual peripheral CD8+ T cell clones, identify baseline markers of CD8+ T cell clonal sensitivity, and chart how CD8+ T cell transcriptional changes vary according to phenotypic subset and clonal size. We identified seven subsets of CD8+ T cells with divergent reactivity to ICB and found that the cytotoxic effector subset showed the greatest number of differentially expressed genes while remaining stable in clonal size after ICB. At the level of CD8+ T cell clonotypes, we found a relationship between transcriptional changes and clone size, with large clones showing a greater number of differentially regulated genes enriched for pathways including T cell receptor (TCR) signaling. Cytotoxic CD8+ effector clones were more likely to persist following ICB and were more likely to correspond with public tumor-infiltrating lymphocyte clonotypes. Last, we demonstrated that individuals whose CD8+ T cell pretreatment showed low cytotoxicity and had fewer expanded clones typically had worse outcomes after ICB treatment. This work further advances understanding of the molecular determinants of ICB response, assisting in the search for peripheral prognostic biomarkers and highlighting the importance of the baseline CD8+ immune landscape in determining ICB response in metastatic melanoma.
Earth history events shaped the evolution of uneven biodiversity across tropical moist forests

Significance Tropical moist forests harbor much of the world’s biodiversity, but this diversity is not evenly distributed globally, with tropical moist forests in the Neotropics and Indomalaya generally exhibiting much greater diversity than in the Afrotropics. Here, we assess the ubiquity of this “pantropical diversity disparity” (PDD) using the present-day distributions of over 150,000 species of plants and animals, and we compare these distributions with a spatial model of diversification combined with reconstructions of plate tectonics, temperature, and aridity. Our study demonstrates that differences in paleoenvironmental dynamics between continents, including mountain building, aridification, and global temperature fluxes, can explain the PDD by shaping spatial and temporal patterns of species origination and extinction, providing a close match to observed distributions of plants and animals. Far from a uniform band, the biodiversity found across Earth’s tropical moist forests varies widely between the high diversity of the Neotropics and Indomalaya and the relatively lower diversity of the Afrotropics. Explanations for this variation across different regions, the “pantropical diversity disparity” (PDD), remain contentious, due to difficulty teasing apart the effects of contemporary climate and paleoenvironmental history. Here, we assess the ubiquity of the PDD in over 150,000 species of terrestrial plants and vertebrates and investigate the relationship between the present-day climate and patterns of species richness. We then investigate the consequences of paleoenvironmental dynamics on the emergence of biodiversity gradients using a spatially explicit model of diversification coupled with paleoenvironmental and plate tectonic reconstructions. Contemporary climate is insufficient in explaining the PDD; instead, a simple model of diversification and temperature niche evolution coupled with paleoaridity constraints is successful in reproducing the variation in species richness and phylogenetic diversity seen repeatedly among plant and animal taxa, suggesting a prevalent role of paleoenvironmental dynamics in combination with niche conservatism. The model indicates that high biodiversity in Neotropical and Indomalayan moist forests is driven by complex macroevolutionary dynamics associated with mountain uplift. In contrast, lower diversity in Afrotropical forests is associated with lower speciation rates and higher extinction rates driven by sustained aridification over the Cenozoic. Our analyses provide a mechanistic understanding of the emergence of uneven diversity in tropical moist forests across 110 Ma of Earth’s history, highlighting the importance of deep-time paleoenvironmental legacies in determining biodiversity patterns.
High resolution diffusion tensor imaging of the hippocampus across the healthy lifespan

The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown age‐related hippocampal volume changes that vary along the anterior–posterior axis. Diffusion tensor imaging (DTI) provides complementary measures related to microstructure, but there are few hippocampus DTI studies investigating change with age in healthy participants, and all have been limited by low spatial resolution. The current study uses high resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5–74 years to investigate diffusion and volume trajectories of the hippocampus (whole, head, body, and tail) and correlations with memory. Hippocampal volume showed age‐related changes that differed between head (peaking at midlife), body (no changes), and tail (decreasing across the age span). Fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD) yielded peaks or minima, respectively, at ~30–35 years in all three subregions of the hippocampus. Greater magnitude changes were observed during development than in aging. Age trajectories for both volume and DTI were similar between males and females. Correlations between tests of memory and FA and/or volume were significant in younger subjects (5–17 years), but not in 18–49 year olds or 50–74 year olds. MD was significantly correlated with memory performance in 18–49 year olds, but not in other age groups. Given the diffusion‐weighted image contrast and resolution, head digitations could be examined revealing that the majority of subjects had 3–4 (48%) or 2 (32%) bilaterally with no effect of age. One millimeter isotropic DTI yielded high quality diffusion‐weighted maps of the human hippocampus that showed regionally specific age effects and cognitive correlations along the anterior–posterior axis from 5 to 74 years.
Associations between health indicators and sleep duration of American adults: NHANES 2011-16.

BACKGROUND This study aimed to investigate associations between health indicators and sleep duration in the general population. METHODS This cross-sectional data from the National Health and Nutrition Examination Survey. Self-reported sleep duration was classified into short sleep (<7 h/day), regular sleep (7-8 h/day) and long sleep duration (>8 h/day). Health indicators included lifestyle indicators (smoking, alcohol use and physical inactivity), general health indicators (waist circumference and self-reported health condition) and chronic conditions [overweight/obesity, hypertension, diabetes, high cholesterol, chronic low back pain (CLBP) and oral health problems]. A series of multinomial logistic regression analysis were performed, controlling for confounders (age, sex, marital status, ethnic background, education level and poverty-to-income ratio). RESULTS Data of 12 835 participants were analyzed. The mean (SD) age of participants was 50.0 (±17.4) years, and 50.6% were women. After adjusting for all health indicators, current smoking (OR: 1.37; 95% CI: 1.17-1.61), a poor (OR: 1.52; 95% CI: 1.23-1.88) health condition, CLBP (OR: 1.40; 95% CI: 1.16-1.69) and oral health problems (OR: 1.28; 95% CI: 1.10-1.49) were associated with short sleep duration. No independent association with long sleep duration was observed in this study. CONCLUSIONS The results confirm that lifestyle indicators (current smoking and physical inactivity), general health indicators (self-reported health condition) and presence of some chronic conditions (CLBP and oral health problems) are associated with short sleep duration. The results did not confirm that any health indicator was associated with long sleep duration.
Adolescents' assessments of consequences of the pandemic after one year of COVID-19 restrictions.

BACKGROUND We have obtained knowledge of how the COVID-19 pandemic affected the lives of adolescents immediately after the pandemic arrived in Norway. However, we know little about adolescents' experiences from the pandemic over time, and whether sociodemographic factors and infection rates at the municipality level play a role. MATERIAL AND METHOD We used questionnaire data from 106 448 lower and upper secondary school pupils who took part in the Ungdata survey in 167 municipalities in the spring of 2021 (response rate 76 %). The adolescents' responses regarding their experiences during the pandemic were collated with statistics on infection rates at the municipality level. We performed a Chi-square test and multilevel analyses to investigate predictors of adolescents' experiences. RESULTS A total of 49 % responded that the COVID-19 pandemic affected their lives in a partly or very negative direction. Many reported negative changes in peer relationships, family relationships and mental health, but some also reported positive changes. Girls, older adolescents, those with a low socioeconomic background and those living in municipalities with a higher prevalence of infection reported more negative consequences. INTERPRETATION Most adolescents reported that the pandemic has had more negative than positive consequences. Girls, older adolescents, those with a low socioeconomic background and those living in municipalities with a higher rate of infection may be especially affected by the negative effects of the pandemic.
Multiplexed Single-Molecule Experiments Reveal Nucleosome Invasion Dynamics of the Cas9 Genome Editor

Single-molecule measurements provide detailed mechanistic insights into molecular processes, for example in genome regulation where DNA access is controlled by nucleosomes and the chromatin machinery. However, real-time single-molecule observations of nuclear factors acting on defined chromatin substrates are challenging to perform quantitatively and reproducibly. Here we present XSCAN (multiplexed single-molecule detection of chromatin association), a method to parallelize single-molecule experiments by simultaneous imaging of a nucleosome library, where each nucleosome type carries an identifiable DNA sequence within its nucleosomal DNA. Parallel experiments are subsequently spatially decoded, via the detection of specific binding of dye-labeled DNA probes. We use this method to reveal how the Cas9 nuclease overcomes the nucleosome barrier when invading chromatinized DNA as a function of PAM position.
Factors associated with COVID-19 viral and antibody test positivity and assessment of test concordance: a retrospective cohort study using electronic health records from the USA

Objectives To identify factors associated with COVID-19 test positivity and assess viral and antibody test concordance. Design Observational retrospective cohort study. Setting Optum de-identified electronic health records including over 700 hospitals and 7000 clinics in the USA. Participants There were 891 754 patients who had a COVID-19 test identified in their electronic health record between 20 February 2020 and 10 July 2020. Primary and secondary outcome measures Per cent of viral and antibody tests positive for COVID-19 (‘positivity rate’); adjusted ORs for factors associated with COVID-19 viral and antibody test positivity; and per cent concordance between positive viral and subsequent antibody test results. Results Overall positivity rate was 9% (70 472 of 771 278) and 12% (11 094 of 91 741) for viral and antibody tests, respectively. Positivity rate was inversely associated with the number of individuals tested and decreased over time across regions and race/ethnicities. Antibody test concordance among patients with an initial positive viral test was 91% (71%–95% depending on time between tests). Among tests separated by at least 2 weeks, discordant results occurred in 7% of patients and 9% of immunocompromised patients. Factors associated with increased odds of viral and antibody positivity in multivariable models included: male sex, Hispanic or non-Hispanic black or Asian race/ethnicity, uninsured or Medicaid insurance and Northeast residence. We identified a negative dose effect between the number of comorbidities and viral and antibody test positivity. Paediatric patients had reduced odds (OR=0.60, 95% CI 0.57 to 0.64) of a positive viral test but increased odds (OR=1.90, 95% CI 1.62 to 2.23) of a positive antibody test compared with those aged 18–34 years old. Conclusions This study identified sociodemographic and clinical factors associated with COVID-19 test positivity and provided real-world evidence demonstrating high antibody test concordance among viral-positive patients.
Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection

Visual Abstract Significance Statement Analyses of the incidence, relative kinetics, and spectrum of anti–SARS-CoV-2 antibodies in kidney transplant recipients are not as detailed as they are for immunocompetent controls. In this multicenter, cross-sectional study of 49 kidney transplant recipients with PCR-confirmed SARS-CoV-2 infection, we found that anti–SARS-CoV-2 IgG production is delayed but that IgM and IgA responses are similar compared with those observed in immunocompetent controls. Therefore, antiviral humoral immunity is delayed but preserved in kidney transplant recipients. This finding is important in understanding the immune response against SARS-CoV-2 in patients on chronic immunosuppression and may provide insights into devising strategies to monitor antibody responses to infection and vaccination. Background Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti–SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1–4, and IgA antibodies against five distinct viral epitopes. Results Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti–SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. Conclusions Kidney transplant recipients mount early anti–SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19. Podcast This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321. mp3