Miracle-dz/UniFAR-FTUs huggingface dataset:
Concurrent Learning Based Dual Control for Exploration and Exploitation in Autonomous Search

—In this paper, a concurrent learning framework is developed for source search in an unknown environment using autonomous platforms equipped with onboard sensors. Distinct from the existing solutions that require signiﬁcant computational power for Bayesian estimation and path planning, the proposed solution is computationally affordable for onboard processors. A new concept of concurrent learning using multiple parallel estimators is proposed to learn the operational environment and quantify estimation uncertainty. The search agent is empowered with dual capability of exploiting current estimated parameters to track the source and probing the environment to reduce the impacts of uncertainty, namely Concurrent Learning for Exploration and Exploitation (CLEE). In this setting, the control action not only minimises the tracking error between future agent’s position and estimated source location, but also the uncertainty of predicted estimation. More importantly, the rigorous proven properties such as the convergence of CLEE algorithm are established under mild assumptions on sensor noises, and the impact of noises on the search performance is examined. Simulation results are provided to validate the effectiveness of the proposed CLEE algorithm. Compared with the information-theoretic approach, CLEE not only guarantees convergence, but produces better search performance and consumes much less computational time.
Welcome to the Pyrocene: Animal survival in the age of megafire

Planet Earth is entering the age of megafire, pushing ecosystems to their limits and beyond. While fire causes mortality of animals across vast portions of the globe, scientists are only beginning to consider fire as an evolutionary force in animal ecology. Here, we generate a series of hypotheses regarding animal responses to fire by adopting insights from the predator–prey literature. Fire is a lethal threat; thus, there is likely strong selection for animals to recognize the olfactory, auditory, and visual cues of fire, and deploy fire avoidance behaviours that maximize survival probability. If fire defences are costly, it follows that intraspecific variation in fire avoidance behaviours should correspond with variation in fire behaviour and regimes. Species and populations inhabiting ecosystems that rarely experience fire may lack these traits, placing ‘fire naive’ populations and species at enhanced extinction risk as the distribution of fire extends into new ecosystem types. We outline a research agenda to understand behavioural responses to fire and to identify conservation interventions that could be used to overcome fire naivety.
Head and eyes: Looking behavior in 12- to 24-month-old infants

This study demonstrates evidence for a foundational process underlying active vision in older infants during object play. Using head-mounted eye-tracking and motion capture, looks to an object are shown to be tightly linked to and synchronous with a stilled head, regardless of the duration of gaze, for infants 12 to 24 months of age. Despite being a developmental period of rapid and marked changes in motor abilities, the dynamic coordination of head stabilization and sustained gaze to a visual target is developmentally invariant during the examined age range. The findings indicate that looking with an aligned head and eyes is a fundamental property of human vision and highlights the importance of studying looking behavior in freely moving perceivers in everyday contexts, opening new questions about the role of body movement in both typical and atypical development of visual attention.
MCML: Combining physical constraints with experimental data for a multi‐purpose meta‐generalized gradient approximation

The predictive power of density functional theory for materials properties can be improved without increasing the overall computational complexity by extending the generalized gradient approximation (GGA) for electronic exchange and correlation to density functionals depending on the electronic kinetic energy density in addition to the charge density and its gradient, resulting in a meta‐GGA. Here, we propose an empirical meta‐GGA model that is based both on physical constraints and on experimental and quantum chemistry reference data. The resulting optimized meta‐GGA MCML yields improved surface and gas phase reaction energetics without sacrificing the accuracy of bulk property predictions of existing meta‐GGA approaches.
Memory and eye movement desensitization and reprocessing therapy: a potentially risky combination in the courtroom

ABSTRACT Does Eye Movement and Desensitization and Reprocessing (EMDR) therapy affect the accuracy of memories? This recurrent issue in recent memory research bears relevance to expert witness work in the courtroom. In this review, we will argue that several crucial aspects of EMDR may be detrimental to memory. First, research has shown that eye movements undermine the quality and quantity of memory. Specifically, eye movements have been shown to decrease the vividness and emotionality of autobiographical experiences and amplify spontaneous false memory levels. Second, a sizeable proportion of EMDR practitioners endorse the controversial idea of repressed memories and discuss the topic of repressed memory in therapy. Third, in the Dutch EMDR protocol, patients are instructed to select the target image by using flawed metaphors of memory (e.g., memory works as a video). Such instructions may create demand characteristics to the effect that people over-interpret imagery during therapy as veridical memories. Collectively, the corpus of research suggests that several components of EMDR therapy (i.e., performing eye movements, therapist beliefs and therapeutic instructions) may undermine the accuracy of memory, which can be risky if patients, later on, serve as witnesses in legal proceedings.
Utility of plasma cell-free DNA detection using homobifunctional imidoesters using a microfluidic system for diagnosing active tuberculosis

Abstract Background It is difficult to diagnose tuberculosis (TB), particularly sputum-scarce pulmonary TB and extrapulmonary TB, using conventional diagnostic tests. Since these cases require additional invasive procedures to obtain appropriate specimens, new non-invasive diagnostic tests are needed. Plasma cell-free DNA (cfDNA) detection has gained interest as a novel diagnostic test for TB as it is convenient and less invasive. Therefore, we investigated the performance of enriched cfDNA for diagnosing pulmonary TB and extrapulmonary TB. Methods All patients suspected to have TB, who consented to the use of blood for detecting cfDNA, were prospectively enrolled from January 2019 to June 2020. We categorised the patients as confirmed, probable, possible TB, and not-TB. We compared the performance of cfDNA with those of conventional diagnostic tests. Results Among the 96 patients enrolled, 40 (41.7%) had TB, including 34 with confirmed TB and six probable TB, and 41 (42.7%) did not have TB. Acid-fast bacilli microscopy, Xpert MTB/RIF, and mycobacterial culture results were positive in 12 (31.6%), 22 (61.1%), and 25 (65.8%) patients, respectively. The sensitivity and specificity of cfDNA were 80.0% and 78.1%, respectively. While the sensitivity and specificity of cfDNA were similar to those of interferon-gamma releasing assay (IGRA) (sensitivity 80.6% and specificity 71.4%), the combined sensitivity and specificity of the two assays were 94.4% and 64.3%, respectively, which can be used to rule out TB. Conclusions Plasma cfDNA assay seems to be a useful adjunct to the current tests for diagnosing TB, especially when used in combination with IGRA for ruling out TB. Abbreviations TB tuberculosis cfDNA cell-free DNA PCR polymerase chain reaction AFB acid-fast bacilli IGRA interferon-gamma releasing assay CT computed tomography HIV human immunodeficiency virus
Establishing the tolerability to broiler chickens and laying hens of nonanoic acid at practical levels of use as a feed flavouring

ABSTRACT 1. The following experiments were conducted to evaluate the effects of nonanoic acid (NA) in broilers and laying hens, at practical levels as a flavouring in complete feed. 2. In the first experiment, 1100, one-day-old Ross 308 chicks, half male and female, were randomly assigned to 50 floor pens containing 22 chicks each. Chicks were fed one of five treatment diets containing either 0 (control), 100, 300, 500 or 1,000 mg NA/kg complete feed for 42 days. 3. The NA treatment had no effect on ADFI, but there was a linear relationship with ADG and FCR. No differences were observed in blood parameters or tissue pathology among treatment groups. 4. In a second study, 150 Hyline hens aged 24 weeks old were randomly assigned to 50 pens containing three birds each. Laying hens were fed one of five treatment diets containing 0 (control), 100, 300, 500 or 1,000 mg NA/kg complete feed for 56 days. 5. Treatment with NA has no effect on live weight, ADFI or egg production in laying hens, and there were no observed changes in tissue pathology. 6. The results supported the toleration of NA in broilers or layers at dietary levels of up to 1,000 mg/kg.
Screening Youth Soccer Players by Means of Cognitive Function and Agility Testing

Talent identification in sports is a heavily debated topic. Previous studies have separately explored either executive functions or gross motor skills to predict the success of top-level soccer players or, more generally, to characterize elite performance in soccer. However, at mid-childhood, the possibility to scope sport-specific requirements remains elusive. We aimed in this study to investigate a valid and simple method of testing for a unique combination of cognitive and speed abilities for identifying promising soccer players at mid-childhood. We measured cognitive functions by means of a Stroop smartphone application and agility with a T-Drill Ball-success test, in two groups of (a) elite- (n = 31) and (b) low-division (n = 37) Italian 7-year-old male soccer players. We administered the tests in a randomized order to both groups. We found better inhibitory control, cognitive flexibility and soccer-specific agility in high-division versus low-division players (p < .001). Inhibitory response and agility were positively associated with the augmented quality of the performance from low-division players to high-division players (r = .55; p = .0001). These results suggest that, even at an early age, cognitive control together with soccer-specific skills is associated with better performance.
Context-sensitivity of isosteric substitutions of non-Watson–Crick basepairs in recurrent RNA 3D motifs

Abstract Sequence variation in a widespread, recurrent, structured RNA 3D motif, the Sarcin/Ricin (S/R), was studied to address three related questions: First, how do the stabilities of structured RNA 3D motifs, composed of non-Watson–Crick (non-WC) basepairs, compare to WC-paired helices of similar length and sequence? Second, what are the effects on the stabilities of such motifs of isosteric and non-isosteric base substitutions in the non-WC pairs? And third, is there selection for particular base combinations in non-WC basepairs, depending on the temperature regime to which an organism adapts? A survey of large and small subunit rRNAs from organisms adapted to different temperatures revealed the presence of systematic sequence variations at many non-WC paired sites of S/R motifs. UV melting analysis and enzymatic digestion assays of oligonucleotides containing the motif suggest that more stable motifs tend to be more rigid. We further found that the base substitutions at non-Watson–Crick pairing sites can significantly affect the thermodynamic stabilities of S/R motifs and these effects are highly context specific indicating the importance of base-stacking and base-phosphate interactions on motif stability. This study highlights the significance of non-canonical base pairs and their contributions to modulating the stability and flexibility of RNA molecules.
Resolvin D1 protects against cadmium chloride-induced memory loss and hippocampal damage in rats: A comparison with docosahexaenoic acid

Background Intoxication with cadmium (Cd) ions leads to hippocampal damage and cognitive impairment. However, omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert neuroprotective effects in different animal models of neurodegeneration. Purpose This study compared the neuroprotective effect of the n-3 PUFA, docosahexaenoic acid (DHA), and its downstream metabolite, resolvin D1 (RVD1), on hippocampal damage and memory deficits in cadmium chloride (CdCl2)-treated rats. Research design Control or CdCl2 (0.5 mg/kg)-treated rats were subdivided into three groups (n = 18/each) and treated for 6 weeks as follows: (1) fed control diet, (2) fed DHA-rich diets (0.7 g/100 g), or (3) treated with RVD1 (0.2 μg/kg, i.p). Results Treatment with a DHA-rich diet or RVD1 significantly increased the levels of docosahexaenoic acid and RVD1, respectively, in the hippocampal of CdCl2-treated rats without affecting the reduction in the expression of the 15-lipooxygenase-1 (ALOX15). These effects were associated with improvements in rats’ memory function and hippocampal structure, as well as a redction in the hippocampal levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear localization of the nuclear factor-kappa beta p65 (NF-κB p65), and expression of cleaved caspase-3. Concomitantly, hippocampi of both groups of rats showed significantly higher levels of Bcl-2, superoxide dismutase (SOD), and glutathione (GSH), as well as enhanced nuclear levels of the nuclear factor erythroid 2–related factor 2 (Nrf-2). The effects of RVD1 on all these markers in the CdCl2-induced rats were more profound than those of DHA. Also, the increase in the nuclear protein levels of Nrf-2 and the decrease in the levels of Bax and nuclear protein levels of NF-κB p65 were only seen in the hippocampal of CdCl2 + RVD1-treated rats. Conclusion RVD1 is more powerful than DHA in preventing CdCl2-induced memory loss and hippocampal damage in rats.
Identification of incompletely penetrant variants and interallelic interactions in autosomal recessive disorders by a population‐genetic approach

We aimed to identify incompletely penetrant (IP) variants and interallelic interactions in autosomal recessive disorders by a population‐genetic approach. Genotype and clinical data were collected from 9038 patients of European origin with ASL, ATP7B, CAPN3, CFTR, CTNS, DHCR7, GAA, GALNS, GALT, IDUA, MUT, NPHS1, NPHS2, PAH, PKHD1, PMM2, or SLC26A4‐related disorders. We calculated the relative allele frequency of each pathogenic variant (n = 1936) to the loss‐of‐function (LOF) variants of the corresponding gene in the patient ( A C p t V / A C p t L O F ) and the general population ( AC gnomAD V / AC gnomAD LOF ) and estimated the penetrance of each variant by calculating their ratio: ( A C p t V / A C p t L O F ) ( A C g n o m A D V / A C g n o m A D L O F ) (V/LOF ratio). We classified all variants as null or hypomorphic based on the associated clinical phenotype. We found 25 variants, 29% of the frequent 85 variants, to be underrepresented in the patient population (V/LOF ratio <30% with p < 7.22 × 10−5), including 22 novel ones in the ASL, CAPN3, CFTR, GAA, GALNS, PAH, and PKHD1 genes. In contrast to the completely penetrant variants (CP), the majority of the IP variants were hypomorphic (IP: 16/18, 88%; CP: 177/933, 19.0%; p = 5.12 × 10−10). Among them, only the NPHS2 R229Q variant was subject to interallelic interactions. The proposed algorithm identifies frequent IP variants and estimates their penetrance and interallelic interactions in large patient cohorts.
Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

Gut microbiota is a potent biological modulator of many physiological and pathological states. The renin-angiotensin system (RAS), including the local gastrointestinal RAS (GI RAS), emerges as a potential mediator of microbiota-related effects. The RAS is involved in cardiovascular system homeostasis, water-electrolyte balance, intestinal absorption, glycemic control, inflammation, carcinogenesis and aging-related processes. Ample evidence suggests a bidirectional interaction between the microbiome and RAS. On the one hand, gut bacteria and their metabolites may modulate GI and systemic RAS. On the other hand, changes in the intestinal habitat caused by alterations in RAS may shape microbiota metabolic activity and composition. Notably, the pharmacodynamic effects of the RAS-targeted therapies may be in part mediated by the intestinal RAS and changes in the microbiome. This review summarizes studies on gut microbiota and RAS physiology. Expanding the research on this topic may lay a foundation for new therapeutic paradigms in gastrointestinal diseases and multiple systemic disorders.
Chlorinated Paraffin Levels in Relation to Other Persistent Organic Pollutants Found in Pooled Human Milk Samples from Primiparous Mothers in 53 Countries

Background: The current production and use of chlorinated paraffins (CPs) at >1 million tons/y likely exceeds the lifetime production of polychlorinated biphenyls (PCBs). These persistent organic pollutants (POPs) are a concern to human health. Objectives: The United Nations Environment Programme conducts global surveys of human milk samples from individual countries as a noninvasive method of investigating levels and trends in human exposures to POPs such as CPs. We measured CP concentrations and assessed their relation to other POPs in pooled samples collected during 2012–2019. Methods: We analyzed 57 official nationwide pooled milk samples from 53 countries on five continents (Africa, Central/South America, Asia, Europe, and Australia/Oceania). CP concentrations were further characterized by subgroups and compared with concentrations of 19 other POPs, including PCBs and a variety of pesticides. Results: CPs were detected in pooled samples from all 53 countries, with concentrations of 23–700 ng/g lipid. CPs accounted for 18–46% of the total summed POPs in human milk, second only to dichlorodiphenyltrichloroethane (DDT). CP concentrations exceeded PCB concentrations in pooled samples from most countries. Discussion: The presence of CPs in all samples, including samples from isolated locations (e.g., Pacific Island countries), emphasizes the ubiquitous presence of these compounds, whereas differences in subgroup ratios indicate a delay in the shift toward nonregulated medium-chain CPs (MCCPs) for these regions. The predominance of MCCPs in samples from many countries suggests a need for regulation and research on health effects. https://doi.org/10.1289/EHP7696
An open‐label, nonrandomized, phase Ib feasibility study of cusatuzumab in patients with nasopharyngeal carcinoma

CD70 is expressed in up to 80% of nasopharyngeal carcinoma (NPC) cases. Cusatuzumab is a humanized anti‐CD70 monoclonal antibody, with dual action mechanisms: induction of cytotoxicity against CD70+ tumor cells and reduction in CD70‐CD27 signaling mediated immune evasion. The aim of this study was to assess the safety, pharmacokinetic profile, immunogenicity, pharmacodynamic profile, and preliminary activity of cusatuzumab in advanced NPC. Eleven patients were enrolled: one patient was assigned to arm A (adjuvant cusatuzumab monotherapy after curative chemoradiation), nine patients to arm B (cusatuzumab monotherapy; noncurative setting), and one patient to arm C (cusatuzumab + chemotherapy; noncurative setting); irrespective of tumoral CD70 expression. Both patients in arms A and C completed the study. All patients in arm B discontinued at an early stage. Five patients experienced grade greater than or equal to 3 nondrug related treatment‐emergent adverse events, most commonly fatigue and pneumonia (18%). An infusion‐related reaction was observed in two of 11 patients. Laboratory results showed no trend over time. Seven patients were eligible for response evaluation. No objective response to cusatuzumab was observed with stable disease being the best response. The current study indicates that the safety profile of cusatuzumab (with or without concurrent chemotherapy) is manageable in patients with advanced NPC, which is consistent with known safety profile. Limited activity of cusatuzumab in advanced NPC was observed. Combination therapies of cusatuzumab and other types of therapy should be explored for the improvement of activity in NPC and other CD70‐expressing malignancies.
Identification of compound heterozygous DNAH11 variants in a Han‐Chinese family with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto‐sino‐pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han‐Chinese pedigree, whole‐exome sequencing was conducted in the 37‐year‐old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice‐site variant. Compound heterozygous variants including a splice‐site variant (c.1974‐1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease‐associated variants of this lineage. The minigene expression in vitro revealed that the c.1974‐1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.
Emotional distress and well-being among people with motor neurone disease (MND) and their family caregivers: a qualitative interview study

Objective We aimed to get an in-depth understanding of the emotions experienced by people with motor neurone disease (MND) and their caregivers, and to explore what impacts emotional distress and well-being. Design Qualitative study using semi-structured interviews with people with MND and caregivers. Setting Participants were recruited from across the UK and took part in interviews conducted either face to face, by telephone or email to accommodate for varying levels of disability. Participants 25 people with MND and 10 caregivers took part. Participants were purposively sampled based on their MND diagnosis, symptoms and time since diagnosis. Data analysis Data were analysed using inductive reflexive thematic analysis. Results Eight broad themes were generated (20 subthemes). Participants described the emotional distress of losing physical function and having a threatened future because of poor prognosis. Keeping up with constant changes in symptoms and feeling unsupported by the healthcare system added to emotional distress. Finding hope and positivity, exerting some control, being kinder to oneself and experiencing support from others were helpful strategies for emotional well-being. Conclusion The study provides a broad understanding of what impacts emotional distress and well-being and discusses implications for psychological interventions for people with MND and caregivers. Any communication and support provided for people with MND and their caregivers, needs to pay attention to concepts of hope, control and compassion.