Miracle-dz/UniFAR-FTUs huggingface dataset:
Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding, with Associated Consequences for Hippocampal Spatial Memory

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology. SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.
Respirators, face masks, and their risk reductions via multiple transmission routes for first responders within an ambulance

Abstract First responders may have high SARS-CoV-2 infection risks due to working with potentially infected patients in enclosed spaces. The study objective was to estimate infection risks per transport for first responders and quantify how first responder use of N95 respirators and patient use of cloth masks can reduce these risks. A model was developed for two Scenarios: an ambulance transport with a patient actively emitting a virus in small aerosols that could lead to airborne transmission (Scenario 1) and a subsequent transport with the same respirator or mask use conditions, an uninfected patient; and remaining airborne SARS-CoV-2 and contaminated surfaces due to aerosol deposition from the previous transport (Scenario 2). A compartmental Monte Carlo simulation model was used to estimate the dispersion and deposition of SARS-CoV-2 and subsequent infection risks for first responders, accounting for variability and uncertainty in input parameters (i.e., transport duration, transfer efficiencies, SARS-CoV-2 emission rates from infected patients, etc.). Infection risk distributions and changes in concentration on hands and surfaces over time were estimated across sub-Scenarios of first responder respirator use and patient cloth mask use. For Scenario 1, predicted mean infection risks were reduced by 69%, 48%, and 85% from a baseline risk (no respirators or face masks used) of 2.9 × 10−2 ± 3.4 × 10−2 when simulated first responders wore respirators, the patient wore a cloth mask, and when first responders and the patient wore respirators or a cloth mask, respectively. For Scenario 2, infection risk reductions for these same Scenarios were 69%, 50%, and 85%, respectively (baseline risk of 7.2 × 10−3 ± 1.0 × 10−2). While aerosol transmission routes contributed more to viral dose in Scenario 1, our simulations demonstrate the ability of face masks worn by patients to additionally reduce surface transmission by reducing viral deposition on surfaces. Based on these simulations, we recommend the patient wear a face mask and first responders wear respirators, when possible, and disinfection should prioritize high use equipment.
Prevention of Acute Lung Injury by a Novel CD14-Inhibitory Receptor Activator of the NF-κB Ligand Peptide in Mice

Although CD14 has been implicated in the initiation of multiple TLR-mediated inflammatory responses to sepsis and sepsis-related acute lung injury (ALI), an inhibitor of CD14, except for neutralizing Abs, has not been developed. A partial peptide, microglial healing peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), derived from the receptor activator of the NF-кB ligand, was recently found to inhibit multiple TLR signaling in the macrophages. Therefore, we hypothesized that the inhibitory effect of MHP1-AcN might be through the inhibition of CD14, a common coreceptor for multiple TLRs. In cultured mouse macrophages, MHP1-AcN was shown to bind to CD14 and compete with LPS for competitive inhibition of CD14, resulting in inhibition of TLR4 signaling, including NF-кB and IFN regulatory factor 3 activation and nuclear translocation. In addition to TLR2, TLR4, and TLR7, MHP1-AcN also inhibited TLR3 signaling and Escherichia coli DNA–induced, CD14-dependent TLR9 signals; however, CpG oligodeoxynucleotide–induced, CD14-independent TLR9 signals were not inhibited in the mouse macrophages. In sepsis-induced ALI mouse model, MHP1-AcN treatment showed the reduction in the expression of IL-6 and CCL2 in both the serum and lung tissues. IL-6 levels in the bronchoalveolar lavage fluid and pathological score were also decreased by MHP1-AcN. Thus, MHP1-AcN, a novel CD14 inhibitor, could be a promising agent for treating sepsis-induced ALI.
The Prognostic Potential of Human Prostate Cancer-Associated Macrophage Subtypes as Revealed by Single-Cell Transcriptomics

Macrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, no differences were observed between macrophages isolated from the tumorous and nontumorous portions of the prostatectomy specimens. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence-free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumor microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication. Implications: The specific macrophage subtypes present in a diseased human prostate have prognostic value, suggesting that the relative proportions of these populations are related to patient outcome. Understanding the relative contributions of these subtypes will not only inform patient prognostication, but will enable personalized immunotherapeutic strategies to increase beneficial populations or reduce detrimental populations.
Population-based incidence and mortality of community-acquired pneumonia in Germany

Background Little information on the current burden of community-acquired pneumonia (CAP) in adults in Germany is available. Methods We conducted a retrospective cohort study using a representative healthcare claims database of approx. 4 million adults to estimate the incidence rates (IR) and associated mortality of CAP in 2015. IR and mortality were stratified by treatment setting, age group, and risk group status. A pneumonia coded in the primary diagnosis position or in the second diagnosis position with another pneumonia-related condition coded in the primary position was used as the base cases definition for the study. Sensitivity analyses using broader and more restrictive case definitions were also performed. Results The overall IR of CAP in adults ≥18 years was 1,054 cases per 100,000 person-years of observation. In adults aged 16 to 59 years, IR for overall CAP, hospitalized CAP and outpatient CAP was 551, 96 and 466 (with a hospitalization rate of 17%). In adults aged ≥60 years, the respective IR were 2,032, 1,061 and 1,053 (with a hospitalization rate of 52%). If any pneumonia coded in the primary or secondary diagnosis position was considered for hospitalized patients, the IR increased 1.5-fold to 1,560 in the elderly ≥60 years. The incidence of CAP hospitalizations was substantially higher in adults ≥18 years with at-risk conditions and high-risk conditions (IR of 608 and 1,552, respectively), compared to adults without underlying risk conditions (IR 108). High mortality of hospitalized CAP in adults ≥18 was observed in-hospital (18.5%), at 30 days (22.9%) and at one-year (44.5%) after CAP onset. Mortality was more than double in older adults in comparison to younger patients. Conclusion CAP burden in older adults and individuals with underlying risk conditions was high. Maximizing uptake of existing vaccines for respiratory diseases may help to mitigate the disease burden, especially in times of strained healthcare resources.
Sexual Development and the Environment: Conclusions from 40 Years of Theory

In this review, we consider the insight that has been gained through theoretical examination of environmental sex determination (ESD) and thermolability – how theory has progressed our understanding of the ecological and evolutionary dynamics associated with ESD, the transitional pathways between different modes of sex determination, and the underlying mechanisms. Following decades of theory on the adaptive benefits of ESD, several hypotheses seem promising. These hypotheses focus on the importance of differential fitness (sex-specific effects of temperature on fitness) in generating selection for ESD, but highlight alternative ways differential fitness arises: seasonal impacts on growth, sex-specific ages of maturation, and sex-biased dispersal. ESD has the potential to generate biased sex ratios quite easily, leading to complex feedbacks between the ecology and evolution of ESD. Frequency-dependent selection on sex acts on ESD-related traits, driving local adaptation or plasticity to restore equilibrium sex ratio. However, migration and overlapping generations (“mixing”) diminish local adaptation and leave each cohort/population with the potential for biased sex ratios. Incorporating mechanism into ecology and evolution models reveals similarities between different sex-determining systems. Dosage and gene regulatory network models of sexual development are beginning to shed light on how temperature sensitivity and thresholds may arise. The unavoidable temperature sensitivity in sex-determining systems inherent to these models suggests that evolutionary transitions between genotypic sex determination (GSD) and temperature-dependent sex determination, and between different forms of GSD, are simple and elegant. Theoretical models are often best-served by considering a single piece of a puzzle; however, there is much to gain from reflecting on all of the pieces together in one integrative picture.
Characteristics of nursing and allied health student placements in the Northern Territory over time (2017-2019) and placement satisfaction.

OBJECTIVE Assess nursing and allied health student satisfaction with their remote Northern Territory integrated learning placement and consideration of future rural/remote work Describe the characteristics of these students Examine changes in student characteristics over time. DESIGN A cross-sectional survey of students and a review of student placement data. SETTING Northern Territory, Australia. PARTICIPANTS Former students having a work integrated learning placement of more than 1 week in the Northern Territory from 2017 to 2019. MAIN OUTCOME MEASURE(S) Agreement with the statements 'This placement has encouraged me to consider living and working in a rural or remote location after I graduate' and 'Overall, I was satisfied with my placement. ' The administrative record review examined student numbers, and placement length over time. RESULTS A total of 341 students responded to the online survey. Overall satisfaction with the placement was very high (93%), and 84% agreed/strongly agreed that the placement had encouraged them to consider working in a rural or remote setting. High-quality clinical supervision and educational resources were associated with overall placement satisfaction. Overall placement satisfaction, prior interest in working remotely and satisfaction with educational resources were associated with consideration of working remotely. The number of students having a placement increased by 29% in 2017 to 2019. The number of placement weeks also increased (35%). CONCLUSIONS The number/placement time of nursing and allied health students has increased in the NT. Satisfaction with remote integrated learning placements is on the important pathway to growing a local health professional workforce in remote and rural settings.
Effect of Virtual Reality Perspective-Taking on Related and Unrelated Contexts

Virtual reality perspective-taking (VRPT) experiences effectively increase both empathy and prosocial behaviors toward related social targets (e.g., cutting down a tree in virtual reality increases concern for the environment). This project tests the prediction that empathy is analogous to a muscle that increases with practice and can transfer to unrelated contexts instead of being a mental state that increases only for a specific context or target. This study examines the extent to which VRPT experiences can train empathic skills that are applied to unrelated social targets and contexts. Two thirds of the participants engaged in VRPT experiences either showing what it is like to become homeless or how ocean acidification affects the marine environment. A third of the participants were in the control condition and did not complete a VRPT task. Results replicate previous findings showing that VRPT tasks increase related context empathy and prosocial behaviors; however, the results on VRPTs effect on empathy and prosocial behaviors for unrelated contexts were mixed. The VRPT ocean acidification task was more effective at inducing empathy for the homeless, an unrelated social target, than the control condition, but the empathy-transfer effect did not occur from the homeless context to the ocean context. Replicating previous work, participants who experienced what it is like to become homeless signed a petition supporting the homeless at significantly higher rates than participants in the control condition. These findings show that transfer of empathy from one context to another is possible, but this transfer does not occur for all contexts.
M A ] 5 J un 2 02 1 SURPRISE ! and When to Schedule It .

Information flow measures, over the duration of a game, the audience’s belief of who will win, and thus can reflect the amount of surprise in a game. To quantify the relationship between information flow and audiences’ perceived quality, we conduct a case study where subjects watch one of the world’s biggest esports events, LOL S10. In addition to eliciting information flow, we also ask subjects to report their rating for each game. We find that the amount of surprise in the end of the game plays a dominant role in predicting the rating. This suggests the importance of incorporating when the surprise occurs, in addition to the amount of surprise, in perceived quality models. For content providers, it implies that everything else being equal, it is better for twists to be more likely to happen toward the end of a show rather than uniformly throughout.
DRLPart: A Deep Reinforcement Learning Framework for Optimally Efficient and Robust Resource Partitioning on Commodity Servers

Workload consolidation is a commonly used approach for improving resource utilization of commodity servers. However, colocated workloads often suffer from significant performance degradations due to resource contention, which makes resource partitioning an important research problem. Partitioning multiple resources coordinately is particularly challenging due to the complex contention behaviors and huge solution space, which is not well-addressed in the literature. In this paper, we propose a deep reinforcement learning (DRL) framework, named DRLPart, for solving the problem of partitioning multiple resources coordinately. DRLPart learns the optimal partitioning decision from easy-to-collect real-time system state, without need of domain knowledge and handcrafted search heuristics. We solve two critical challenges of applying DRL to the resource partitioning problem. First, we build a deep-learning based performance model, which significantly reduces the training overhead, by estimating the rewards of actions without interacting with real system. Second, we propose a fine-tuning process to improve bad decisions occasionally made by the DRL model, which enhances the adaptivity to new situations. Results from extensive evaluations show that the proposed framework is optimally efficient and robust, which improves the system throughput by 13.3%~18.5 compared to the state-of-the-art baselines.
Quantitation of corticosterone-induced splenic dendritic cell loss, recovery and prevention in C57BL/6 mice

Abstract. Dendritic cells (DCs) link the innate and adaptive immune response by capturing antigen to present to and activate naïve T cells. Subsets of DCs vary based on protein expression, which allows for their identification. This research focused on total DCs (CD11c+), and the conventional DC subsets (cDC1 and cDC2). Corticosterone (CORT), a stress-induce glucocorticoid hormone, reduces DC numbers and alters DC function and subsequent T cell responses. The current study quantifies DC recovery after CORT exposure and demonstrates that the loss of DCs can be prevented. Mice were exposed to exogenous CORT in the drinking water for 24 hours. CORT exposure significantly decreased the numbers of all splenic DCs. Mice were then provided varying recovery times (3, 5, or 10 days) post-CORT exposure. DCs quickly returned to normal levels, and even exceeded the percentages in control untreated mice. Studies have shown that injection of mice with anti-CD40 antibody triggers DC maturation and proliferation. Thus, it was hypothesized that injection of anti-CD40 may prevent the CORT-induced loss of DCs. Mice received two injections of anti-CD40 antibody over two days and were then immediately supplied with CORT. When provided anti-CD40 prior to CORT, the loss of DCs was prevented. These studies contribute to the ongoing exploration of the mechanisms underlying the immunological effects of stress-induced glucocorticoids.
Deception in weight-loss advertising: Newspaper use of press releases issued by the Federal Trade Commission

The Federal Trade Commission (FTC) regulates advertising associated with dietary supplements, acting for consumers in cases of deception. This study examines the extent to which regional and national newspapers responded to 177 FTC press releases about deceptive claims associated with weight-loss supplements. Of 177 FTC press releases, 77 (43.5%) received at least some coverage in 212 newspaper reports; however, a relatively small number of releases accounted for the preponderance of coverage. Marked increases in news reports at certain points reflected FTC press releases involving multiple companies, new initiatives and the “superfood” acai berry.
Bottom-up but not Top-down Attention Dominates the Value Representation in the Orbitofrontal Cortex

The orbitofrontal cortex (OFC) is essential for value-based learning and decision making. Understanding the attentional modulation of the representation of value in the OFC provides us key information on its functional roles and links the OFC to other cognitive processes. We examined how top-down and bottom-up attention modulates the value encoding in the OFC. Two macaque monkeys were trained to detect a luminance change at a cued location between a pair of visual stimuli, which were over-trained pictures associated with different amount of juice rewards and, thus, different salience. While the monkeys’ behavior and the DLPFC neuronal activities indicated that the monkeys actively directed their attention toward the cued location during the task, the OFC neurons’ value encoding, however, was dominated by the bottom-up attention based on stimulus salience and only reflected the top-down attention weakly. The disassociation between the top-down and bottom-up attention signals in the OFC indicates that the OFC occupies an early stage of value information processing in the brain.
Single-nucleus transcriptomes reveal functional and evolutionary properties of cell types in the Drosophila accessory gland

Many traits responsible for male reproduction evolve quickly, including gene expression phenotypes in germline and somatic male reproductive tissues. Rapid male evolution in polyandrous species is thought to be driven by competition among males for fertilizations and conflicts between male and female fitness interests that manifest in post-copulatory phenotypes. In Drosophila, seminal fluid proteins secreted by three major cell types of the male accessory gland and ejaculatory duct are required for female sperm storage and use, and influence female post-copulatory traits. Recent work has shown that these cell types have overlapping but distinct effects on female post-copulatory biology, yet relatively little is known about their evolutionary properties. Here we use single-nucleus RNA-Seq of the accessory gland and ejaculatory duct from Drosophila melanogaster and two closely related species to comprehensively describe the cell diversity of these tissues and their transcriptome evolution for the first time. We find that seminal fluid transcripts are strongly partitioned across the major cell types, and expression of many other genes additionally define each cell type. We also report previously undocumented diversity in main cells. Transcriptome divergence was found to be heterogeneous across cell types and lineages, revealing a complex evolutionary process. Furthermore, protein adaptation varied across cell types, with potential consequences for our understanding of selection on male post-copulatory traits. SIGNIFICANCE STATEMENT Rapid evolution of male traits may result from competition among males or antagonistic interactions between the sexes over control of reproduction. In animals with internal fertilization, interactions may occur in the female reproductive tract. Drosophila seminal fluid proteins, which are secreted by three major cell types of the male accessory gland and ejaculatory duct, are required for female sperm storage and use, and influence female behavior and physiology. These cell types have distinct effects on females, yet relatively little is known about their evolutionary properties. Here we characterize diversity and transcriptome evolution of seminal fluid-producing tissues at the cell level. These data reveal new functional properties of these cells and complex evolutionary patterns that vary across cell types and lineages.