Miracle-dz/UniFAR-FTUs huggingface dataset:
Prenatal exposure to pesticide residues in the diet in association with child autism‐related traits: Results from the EARLI study

Prior work has suggested associations between prenatal exposure to several classes of pesticides and child autism spectrum disorder (ASD). We examined a previously developed pesticide residue burden score (PRBS) and intake of high pesticide residue foods in association with ASD‐related traits. Participants were drawn from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 256), a cohort following mothers who previously had a child with ASD through a subsequent pregnancy and that child's development. ASD‐related traits were captured according to total Social Responsiveness Scale (SRS) scores at age 3 (mean raw total SRS score = 35.8). Dietary intake was assessed through a food frequency questionnaire collected during pregnancy. We also incorporated organic intake and fatty foods in modified versions of the PRBS. Associations between high‐residue fruit and vegetable intake, the overall PRBS and modified versions of it, and SRS scores were assessed using multivariable linear regression. Overall, we did not observe associations between pesticide residues in foods and ASD‐related outcomes, and modified versions of the PRBS yielded similar findings. However, reductions in ASD‐related traits were observed with higher overall fruit and vegetable intake (adjusted estimates for Q4 vs. Q1: β −12.76, 95%CI −27.8, 2.3). Thus, findings from this high familial probability cohort did not suggest relationships between pesticide residues in the diet according to the PRBS and ASD‐related traits. Beneficial effects of fruit and vegetable intake may influence these relationships. Future work should consider fruit and vegetable intake in association with ASD‐related outcomes.
Tomato brown rugose fruit virus resistance generated by quadruple knockout of homologs of TOBAMOVIRUS MULTIPLICATION1 in tomato

Abstract Tomato brown rugose fruit virus (ToBRFV) is an emerging virus of the genus Tobamovirus. ToBRFV overcomes the tobamovirus resistance gene Tm-22 and is rapidly spreading worldwide. Genetic resources for ToBRFV resistance are urgently needed. Here, we show that clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis of four tomato (Solanum lycopersicum) homologs of TOBAMOVIRUS MULTIPLICATION1 (TOM1), an Arabidopsis (Arabidopsis thaliana) gene essential for tobamovirus multiplication, confers resistance to ToBRFV in tomato plants. Quadruple-mutant plants did not show detectable ToBRFV coat protein (CP) accumulation or obvious defects in growth or fruit production. When any three of the four TOM1 homologs were disrupted, ToBRFV CP accumulation was detectable but greatly reduced. In the triple mutant, in which ToBRFV CP accumulation was most strongly suppressed, mutant viruses capable of more efficient multiplication in the mutant plants emerged. However, these mutant viruses did not infect the quadruple-mutant plants, suggesting that the resistance of the quadruple-mutant plants is highly durable. The quadruple-mutant plants also showed resistance to three other tobamovirus species. Therefore, tomato plants with strong resistance to tobamoviruses, including ToBRFV, can be generated by CRISPR/Cas9-mediated multiplexed genome editing. The genome-edited plants could facilitate ToBRFV-resistant tomato breeding.
Prevalence of Cannabidiol, Δ9- and Δ8-Tetrahydrocannabinol and Metabolites in Workplace Drug Testing Urine Specimens.

Given the recent popularity of cannabidiol (CBD) use and the emergence of Δ8-tetrahydrocannabinol (Δ8-THC), the prevalence and concentration of these and other cannabinoids was investigated in 2,000 regulated and 4,000 non-regulated specimens from workplace drug testing. All specimens were screened using LC-MS-MS for the presence of 7-hydroxy-CBD (7-OH-CBD) and ∆9-tetrahydrocannabinol-9-carboxylic acid (Δ9-THC-COOH), with a cutoff of 2 ng/mL. Specimens screening positive by LC-MS-MS were analyzed by immunoassay at 20, 50 and 100 ng/mL cutoffs, and by an LC-MS-MS confirmation method for 11 cannabinoids and metabolites with a 1 ng/mL cutoff. Using a 1 ng/mL cutoff, 98 (4.9%) regulated and 331 (8.3%) non-regulated specimens were positive for Δ9-THC-COOH. Of these, 64% had concentrations below 15 ng/mL. Similarly, 59 (3.0%) regulated and 162 (4.2%) non-regulated specimens were positive for 7-OH-CBD (n=210), CBD (n=120) and/or 7-carboxy-cannabidiol (CBD-COOH, n=120). The median concentrations of 7-OH-CBD, CBD and CBD-COOH in those 221 specimens were 6.3, 1.1 and 1.2 ng/mL, respectively. Δ8-Tetrahydrocannabinol-9-carboxylic acid (Δ8-THC-COOH) was identified in 76 (1.3%) specimens. Parent Δ8-THC is a minor cannabinoid in marijuana, which appears to account for the typically low Δ8-THC-COOH concentrations (median 3.4 ng/mL) in most positive specimens. However, elevated concentrations suggested use of Δ8-THC-containing products in some cases (range 1.0-415 ng/mL). Although 93% agreement was observed between confirmatory LC-MS-MS (15 ng/mL cutoff) and immunoassay (50 ng/mL cutoff), a false negative specimen (66 ng/mL Δ9-THC-COOH) was identified.
Regulation of early cerebellar development

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three‐layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.
Assessing the potential of wearable health monitors for health system strengthening in low- and middle-income countries: a prospective study of technology adoption in Cambodia

Abstract Wearable health monitors are a rapidly evolving technology that may offer new opportunities for strengthening health system responses to cardiovascular and other non-communicable diseases (NCDs) in low- and middle-income countries (LMICs). In light of this, we explored opportunities for, and potential challenges to, technology adoption in Cambodia, considering the complexity of contextual factors that may influence product uptake and sustainable health system integration. Data collection for this study involved in-depth interviews with national and international stakeholders and a literature review. The analytical approach was guided by concepts and categories derived from the non-adoption, abandonment, scale-up, spread, and sustainability (NASSS) framework—an evidence-based framework that was developed for studying health technology adoption and the challenges to scale-up, spread and sustainability of such technologies in health service organizations. Three potential applications of health wearables for the prevention and control of NCDs in Cambodia were identified: health promotion, follow-up and monitoring of patients and surveys of NCD risk factors. However, several challenges to technology adoption emerged across the research domains, associated with the intended adopters, the organization of the national health system, the wider infrastructure, the regulatory environment and the technology itself. Our findings indicate that, currently, wearables could be best used to conduct surveys of NCD risk factors in Cambodia and in other LMICs with similar health system profiles. In the future, a more integrated use of wearables to strengthen monitoring and management of patients could be envisaged, although this would require careful consideration of feasibility and organizational issues.
Inhibitors of PARP: Number crunching and structure gazing

Significance PARP is an important target in the treatment of cancers, particularly in patients with breast, ovarian, or prostate cancer that have compromised homologous recombination repair (i.e., BRCA−/−). This review about inhibitors of PARP (PARPi) is for readers interested in the development of next-generation drugs for the treatment of cancer, providing insights into structure–activity relationships, in vitro vs. in vivo potency, PARP trapping, and synthetic lethality.
A novel cell line from human eccrine sweat gland duct cells for investigating sweating physiology

Human eccrine sweat glands (eSG) represent vital components of the skin involved in regulating body temperature. Especially the eccrine duct, which opens directly into the skin surface and releases the aqueous sweat, constitutes the first contact point with topically applied substances. For scientific investigations and to understand the underlying sweating mechanism on a cellular level defined cellular material is beneficial. We, therefore, strived to generate a cell line derived from human eSG duct cells for identifying new mechanisms in sweating control, as such a standardized cell line is currently lacking.
Hepatic glucocorticoid‐induced transcriptional regulation is androgen‐dependent after chronic but not acute glucocorticoid exposure

Glucocorticoids exert their pleiotropic effects by activating the glucocorticoid receptor (GR), which is expressed throughout the body. GR‐mediated transcription is regulated by a multitude of tissue‐ and cell type‐specific mechanisms, including interactions with other transcription factors such as the androgen receptor (AR). We previously showed that the transcription of canonical glucocorticoid‐responsive genes is dependent on active androgen signaling, but the extent of this glucocorticoid‐androgen crosstalk warrants further investigation. In this study, we investigated the overall glucocorticoid‐androgen crosstalk in the hepatic transcriptome. Male mice were exposed to GR agonist corticosterone and AR antagonist enzalutamide in order to determine the extent of androgen‐dependency after acute and chronic exposure. We found that a substantial proportion of the hepatic transcriptome is androgen‐dependent after chronic exposure, while after acute exposure the transcriptomic effects of glucocorticoids are largely androgen‐independent. We propose that prolonged glucocorticoid exposure triggers a gradual upregulation of AR expression, instating a situation of androgen dependence which is likely not driven by direct AR‐GR interactions. This indirect mode of glucocorticoid‐androgen interaction is in accordance with the absence of enriched AR DNA‐binding near AR‐dependent corticosterone‐regulated genes after chronic exposure. In conclusion, we demonstrate that glucocorticoid effects and their interaction with androgen signaling are dependent on the duration of exposure and believe that our findings contribute to a better understanding of hepatic glucocorticoid biology in health and disease.
Atrial Structural Remodeling in Patients With Atrial Fibrillation Is a Diffuse Fibrotic Process: Evidence From High‐Density Voltage Mapping and Atrial Biopsy

Background Low‐voltage areas (LVAs) in the atria of patients with atrial fibrillation are considered local fibrosis. We hypothesized that voltage reduction in the atria is a diffuse process associated with fibrosis and that the presence of LVAs reflects a global voltage reduction. Methods and Results We examined 140 patients with atrial fibrillation and 13 patients with a left accessory pathway (controls). High‐density bipolar voltage mapping was performed using a grid‐mapping catheter during high right atrial pacing. Global left atrial (LA) voltage (VGLA) in the whole LA and regional LA voltage (VRLA) in 6 anatomic regions were evaluated with the mean of the highest voltage at a sampling density of 1 cm2. Patients with atrial fibrillation were categorized into quartiles by VGLA. LVAs were evaluated at voltage cutoffs of 0.1, 0.5, 1.0, and 1.5 mV. Twenty‐eight patients with atrial fibrillation also underwent right atrial septum biopsy, and the fibrosis extent was quantified. Voltage at the biopsy site (Vbiopsy) was recorded. VGLA results by category were Q1 (<4.2 mV), Q2 (4.2–5.6 mV), Q3 (5.7–7.0 mV), and Q4 (≥7.1 mV). VRLA at any region was reduced as VGLA decreased. VGLA and VRLA did not differ between Q4 and controls. The presence of LVAs increased as VGLA decreased at any voltage cutoff. Biopsies revealed 11±6% fibrosis, which was inversely correlated with both Vbiopsy and VGLA (r=–0.71 and –0.72, respectively). Vbiopsy was correlated with VGLA (r=0.82). Conclusions Voltage reduction in the LA is a diffuse process associated with fibrosis. Presence of LVAs reflects diffuse voltage reduction of the LA.
Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection, cell stress, neuronal disease, and tumors. Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity. The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27, its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases. Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system. Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain. Interleukin-27 is secreted from and binds to infiltrating microglia, macrophage, astrocytes, and even neurons and it promotes neuronal survival by regulating pro- and anti-inflammatory cytokines, neuroinflammatory pathways, oxidative stress, apoptosis, autophagy, and epigenetic modifications. However, interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations. In this review, we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain, spinal cord, and retina. We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.
Sample-Based Output-Feedback Navigation with Bearing Measurements

We consider the problem of sample-based feedback-based motion planning from bearing (direction-only) measurements. We build on our previous work that defines a cell decomposition of the environment using RRT*, and finds an output feedback controller to navigate through each cell toward a goal location using duality, Control Lyapunov and Barrier Functions (CLF, CBF), and Linear Programming. In this paper, we propose a novel strategy that uses relative bearing measurements with respect to a set of landmarks in the environment, as opposed to full relative displacements. The main advantage is then that the measurements can be obtained using a simple monocular camera. We test the proposed algorithm in the simulation, and then in an experimental environment to evaluate the performance of our approach with respect to practical issues such as mismatches in the dynamical model of the robot, and measurements acquired with a camera with a limited field of view.
Social Engineering Attacks and Defenses in the Physical World vs. Cyberspace: A Contrast Study

Social engineering attacks are phenomena that are equally applicable to both the physical world and cyberspace. These attacks in the physical world have been studied for a much longer time than their counterpart in cyberspace. This motivates us to investigate how social engineering attacks in the physical world and cyberspace relate to each other, including their common characteristics and unique features. For this purpose, we propose a methodology to unify social engineering attacks and defenses in the physical world and cyberspace into a single framework, including: (i) a systematic model based on psychological principles for describing these attacks; (ii) a systematization of these attacks; and (iii) a systematization of defenses against them. Our study leads to several insights, which shed light on future research directions towards adequately defending against social engineering attacks in cyberspace.
PUTN: A Plane-fitting based Uneven Terrain Navigation Framework

Autonomous navigation of ground robots has been widely used in indoor structured 2D environments, but there are still many challenges in outdoor 3D unstructured environments, especially in rough, uneven terrains. This paper proposed a plane-fitting based uneven terrain navigation framework (PUTN) to solve this problem. The implementation of PUTN is divided into three steps. First, based on Rapidly-exploring Random Trees (RRT), an improved sample-based algorithm called Plane Fitting RRT*(PF- RRT*) is proposed to obtain a sparse trajectory. Each sampling point corresponds to a custom traversability index and a fitted plane on the point cloud. These planes are connected in series to form a traversable “strip”. Second, Gaussian Process Regression is used to generate traversability of the dense trajectory interpolated from the sparse trajectory, and the sampling tree is used as the training set. Finally, local planning is performed using nonlinear model predictive control (NMPC). By adding the traversability index and uncertainty to the cost function, and adding obstacles generated by the real-time point cloud to the constraint function, a safe motion planning algorithm with smooth speed and strong robustness is available. Experiments in real scenarios are conducted to verify the effectiveness of the method. The source code is released for the reference of the community11Source code: https://github.com/jianzhuozhuTHU/putn.
A Unified Transformer Framework for Group-Based Segmentation: Co-Segmentation, Co-Saliency Detection and Video Salient Object Detection

Humans tend to mine objects by learning from a group of images or several frames of video since we live in a dynamic world. In the computer vision area, many researchers focus on co-segmentation (CoS), co-saliency detection (CoSD) and video salient object detection (VSOD) to discover the co-occurrent objects. However, previous approaches design different networks for these similar tasks separately, and they are difficult to apply to each other. Besides, they fail to take full advantage of the cues among inter- and intra-feature within a group of images. In this paper, we introduce a unified framework to tackle these issues from a unified view, term as UFGS (Unified Framework for Group-based Segmentation). Specifically, we first introduce a transformer block, which views the image feature as a patch token and then captures their long-range dependencies through the self-attention mechanism. This can help the network to excavate the patch-structured similarities among the relevant objects. Furthermore, we propose an intra-MLP learning module to produce self-mask to enhance the network to avoid partial activation. Extensive experiments on four CoS benchmarks (PASCAL, iCoseg Internet and MSRC), three CoSD benchmarks (Cosal2015, CoSOD3k, and CocA) and five VSOD benchmarks (DAVIS$_{16}$, FBMS, ViSal, SegV2, and DAVSOD) show that our method outperforms other state-of-the-arts on three different tasks in both accuracy and speed by using the same network architecture, which can reach 140 FPS in real-time.
The Directed Probabilistic Powerspace

Probabilistic powerdomain in domain theory plays an important role in modeling the semantics of nondeterministic functional programming languages with probabilistic choice. In this paper, we extend the notion of powerdomain to directed spaces, which is equivalent to the notion of the T0 monotone-determined space [4]. We construct the probabilistic powerspace of the directed space, which is definded as a free directed space-cone. In addition, the relationships between our construction and classical probabilistic powerdomain are studied.
The Severity Prediction of The Binary And Multi-Class Cardiovascular Disease - A Machine Learning-Based Fusion Approach

In today's world, a massive amount of data is available in almost every sector. This data has become an asset as we can use this enormous amount of data to find information. Mainly health care industry contains many data consisting of patient and disease-related information. By using the machine learning technique, we can look for hidden data patterns to predict various diseases. Recently CVDs, or cardiovascular disease, have become a leading cause of death around the world. The number of death due to CVDs is frightening. That is why many researchers are trying their best to design a predictive model that can save many lives using the data mining model. In this research, some fusion models have been constructed to diagnose CVDs along with its severity. Machine learning(ML) algorithms like artificial neural network, SVM, logistic regression, decision tree, random forest, and AdaBoost have been applied to the heart disease dataset to predict disease. Randomoversampler only for multi-class classification to make the imbalanced dataset balanced. To improve the performance of classification, a weighted score fusion approach was taken. At first, the models were trained. After training, two algorithms' decision was combined using a weighted sum rule. A total of three fusion models have been developed from the six ML algorithms. The results were promising in the performance parameter. The proposed approach has been experimented with different test training ratios for binary and multiclass classification problems, and for both of them, the fusion models performed well. The highest accuracy for multiclass classification was found as 75%, and it was 95% for binary.
Trouble in Paradox

: Recent developments in holography have suggested a potential resolution to the black hole information paradox within the context of gravitational eﬀective ﬁeld theory. We emphasize the non-local nature of this proposed resolution, and highlight the ways in which observations outside the black hole can detect it and conclude that the black hole is not radiating like an ordinary body would.