Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene × Environment Interaction in Developmental Disorders: Where Do We Stand and What’s Next?

Although the field of psychiatry has witnessed the proliferation of studies on Gene × Environment (G×E) interactions, still limited is the knowledge we possess of G×E interactions regarding developmental disorders. In this perspective paper, we discuss why G×E interaction studies are needed to broaden our knowledge of developmental disorders. We also discuss the different roles of hazardous versus self-generated environmental factors and how these types of factors may differentially engage with an individual’s genetic background in predicting a resulting phenotype. Then, we present examplar studies that highlight the role of G×E in predicting atypical developmental trajectories as well as provide insight regarding treatment outcomes. Supported by these examples, we explore the need to move beyond merely examining statistical interactions between genes and the environment, and the motivation to investigate specific genetic susceptibility and environmental contexts that drive developmental disorders. We propose that further parsing of genetic and environmental components is required to fully understand the unique contribution of each factor to the etiology of developmental disorders. Finally, with a greater appreciation of the complexities of G×E interaction, this discussion will converge upon the potential implications for clinical and translational research.
Association of TRPV1 and TLR4 through the TIR domain potentiates TRPV1 activity by blocking activation-induced desensitization

Background We have previously reported that histamine-induced pruritus was attenuated in toll-like receptor 4 (TLR4) knockout mice due to decreased transient receptor potential V1 (TRPV1) sensitivity. Our results implied that TLR4 potentiated TRPV1 activation in sensory neurons; however, the molecular mechanism has yet to be elucidated. In this study, we investigated the molecular mechanisms of TLR4-mediated TRPV1 potentiation using TLR4-deficient sensory neurons and a heterologous expression system. Methods Primary sensory neurons were obtained from wild-type or TLR4 knockout mice, and HEK293T cells expressing TRPV1 and TLR4 were prepared by transient transfection. TRPV1 activity was analyzed by calcium imaging, fluorophotometry, and patch-clamp recording. Subcellular protein distribution was tested by immunocytochemistry and cell surface biotinylation assay. Protein interaction was assessed by western blot and immunoprecipitation assay. Results Direct association between TRPV1 and TLR4 was detected in HEK293T cells upon heterologous TRPV1 and TLR4 expression. In an immunoprecipitation assay using TLR4-deletion mutants and soluble toll/interleukin-1 receptor (TIR) protein, the cytoplasmic TIR domain of TLR4 was required for TLR4-TRPV1 association and TRPV1 potentiation. In TLR4-deficient sensory neurons, the activation-induced desensitization of TRPV1 increased, accompanied by enhanced TRPV1 clearance from the cell membrane upon activation compared to wild-type neurons. In addition, heterologous TLR4 expression inhibited activation-induced TRPV1 endocytosis and lysosomal degradation in HEK293T cells. Conclusion Our data show that direct association between TRPV1 and TLR4 through the TIR domain enhances TRPV1 activity by blocking activation-induced TRPV1 desensitization.
Patient–physician relationship – Communication is the key

Patient–physician relationship is a complex psychosocial interplay of vulnerability, trust, and authority in a professional setting. It has been legally defined as “a consensual relationship in which the patient knowingly seeks the physician’s assistance and the physician knowingly accepts the person as a patient. ”[1] Patient–physician relationship is fiduciary, in which a physician is trusted to provide an accepted standard of medical care in his or her area of specialization. [2] Physician’s obligations are to duly inform the patient of the medical condition, to provide optimal treatment, to refer the patient to an appropriate specialist if necessary, and to obtain the patient’s informed consent for medical treatment or surgery. [3] Physicians are influential in deciding if, when, and how healthcare services are delivered, and the balance of power is tipped in favor of the physician. [4] Patients are, therefore, vulnerable when they entrust physicians with their health and lives. Trust is the keystone in such an asymmetrical relationship. [5]
Microencapsulation of blackberry pulp with arrowroot starch and gum arabic mixture by spray drying

Abstract This research work aimed to obtain blackberry pulp powder by spray drying and, by an experimental design, evaluated the effect of inlet air temperature (100–150 °C) and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2 on the physicochemical properties of the powders. Arrowroot starch and gum arabic present glass transition temperature (Tg) values above 100 °C; hence it was possible to employ them as carriers in blackberry pulp spray drying in order to increase Tg of the system. Powder yield and solubility increased with increasing blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2, whereas hygroscopicity decreased. Yield, solubility and hygroscopicity of the powders increased and water activity decreased, with increasing inlet air temperature. The powders presented low moisture content and water activity. Temperature of 143 °C and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:1.78 were the optimal conditions to obtain high yield and blackberry powders that are soluble in water and less hygroscopic.
Planecell: Representing Structural Space with Plane Elements

Reconstruction based on the stereo camera has received considerable attention recently, but two particular challenges still remain. The first concerns the need to present and compress data in an effective way, and the second is to maintain as much of the available information as possible while ensuring sufficient accuracy. To overcome these issues, we propose a new 3D representation method, namely, planecell, that extracts planarity from the depth-assisted image segmentation and then directly projects these depth planes into the 3D world. The proposed method demonstrates its advancement especially dealing with large-scale structural environment, such as autonomous driving scene. The reconstruction result of our method achieves equal accuracy compared to dense point clouds and compresses the output file 200 times. To further obtain global surfaces, an energy function formulated from Conditional Random Field that generalizes the planar relationships is maximized. We evaluate our method with reconstruction baselines on the KITTI outdoor scene dataset, and the results indicate the superiorities compared to other 3D space representation methods in accuracy, memory requirements and the scope of applications.
Comparison of observers for vehicle yaw rate estimation

This paper presents a comparison of observers for vehicle lateral dynamics. Three model-based observers are compared: firstly Luenberger observer with a linear stationary model, secondly Kalman filter with a non stationary model and lastly Luenberger observers for each subsystems of a Takagi-Sugeno multi-model. Moreover, an analysis of the lateral dynamics shows that the model discretisation may be problematic according to the signal sampling theorem and a solution is proposed, such that all the observers can be used on board of the vehicle.
Modeling the Special Intersection for Enhanced Digital Map

The enhanced digital map is of great significance for various Intelligent Transportation System (ITS) applications and services, especially at the lane-level. This requirement motives the development of road modeling in the enhanced digital map at the lane-level. However, previous enhanced digital maps do not provide detailed modeling of special intersections which are covered by vegetation in the central region. In this paper we propose a novel lane-level road model for this special intersection scenario. The proposed intersection model can be considered into two levels: topological structure and geometrical structure. Topological structure of this model helps describe the connectivity, turn restrictions and other attributes of the special intersection in the real world. Geometrical structure of this model helps describe the virtual lanes of the internal part of the special intersection using cardinal spline, which better approximates the real vehicle trajectory at the intersection. The proposed intersection model has been verified and evaluated through experiments. The results demonstrate the effectiveness of the proposed intersection model in representing the lane-level topological and geometrical details of special intersection which is covered by vegetation in its central region.
Inhibitory Effect of Japanese Traditional Kampo Formula Frequently Prescribed in Gynecological Clinics on CYP3A4

Recently, the use of herbal medicines has become popular, and information on drug interactions between herbal medicines and chemical drugs is needed in clinics. In Japan, the number of patients taking Japanese traditional Kampo medicines has been increasing, and the proper drug information about herb-drug interaction is highly demanded. The most established herb-drug interaction is the case of grapefruit juice (GFJ) via the inhibition on CYP3A4 expressed in the small intestine. In the present study, we compared the inhibitory titer on CYP3A4 between the target Kampo products and GFJ used as positive control. We evaluated the inhibitory effects of GFJ and three extracts of Kampo formulas frequently used in gynecological clinics on CYP3A4 in vitro and calculated the related titer of one-time dosage of Kampo formulas to GFJ in order to predict its effect on clinics. Although the extracts of these three Kampo formulas and the most of crude drug components in the formulas exhibited the inhibitory effects on CYP3A4 in some levels, the possibilities of tokishakuyakusan and keishibukuryogan to cause drug interaction can be quite low; however, it is possible that the excessive dosage of kamishoyosan may cause drug interaction with the substrate of CYP3A4 in clinics.
Physical inactivity: productivity losses and healthcare costs 2002 and 2016 in Sweden

Objectives To estimate the costs associated with physical inactivity in Sweden for the year 2016. Methods The costs associated with insufficient physical activity was calculated employing population attributable fractions (PAFs) and register information on healthcare utilisation, mortality and disability pensions. The PAFs were calculated using information on exercise habits and morbidity-specific relative risks. The healthcare cost components were calculated based on registry data on inpatient-care, outpatient-care and primary care utilisation. Registry data on cause-specific mortality and granted disability pensions were used to calculate the productivity loss components. Costs associated with pharmaceutical utilisation were not included due lack of data. Results Physical exercise habits improved somewhat between 2002 and 2016. Thus, the associated morbidity-specific PAFs decreased over the same time period. Conclusions The economic costs attributable to insufficient physical activity decrease between the year 2002 and 2016. Healthcare costs attributable to insufficient physical activity as share of total healthcare expenses increased from 0.86 % in 2002 to 0.91 % in 2016.
Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies

Abstract Background Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls. Methods Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage. Results In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = −0.22; p = 0.29). Conclusions In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.
Pseudomonas aeruginosa LptE is crucial for LptD assembly, cell envelope integrity, antibiotic resistance and virulence

ABSTRACT Lipopolysaccharide (LPS) is an essential structural component of the outer membrane (OM) of most Gram-negative bacteria. In the model organism Escherichia coli, LPS transport to the OM requires seven essential proteins (LptABCDEFG) that form a continuous bridge across the cell envelope. In Pseudomonas aeruginosa the recently-demonstrated essentiality of LptD and LptH, the P. aeruginosa LptA homologue, confirmed the crucial role of the Lpt system and, thus, of LPS in OM biogenesis in this species. Surprisingly, independent high-throughput transposon mutagenesis studies identified viable P. aeruginosa insertion mutants in the lptE gene, suggesting that it might be dispensable for bacterial growth. To test this hypothesis, we generated an lptE conditional mutant in P. aeruginosa PAO1. LptE depletion only slightly impairs P. aeruginosa growth in vitro. Conversely, LptE is important for cell envelope stability, antibiotic resistance and virulence in an insect model. Interestingly, the maturation and OM localization of LPS is only marginally affected in LptE-depleted cells, while the levels of the OM component LptD are strongly reduced. This suggests that P. aeruginosa LptE might not be directly involved in LPS transport, although it is clearly essential for the maturation and/or stability of LptD. While poor functionality of LptD caused by LptE depletion is somehow tolerated by P. aeruginosa, this has a high cost in terms of cell integrity, drug resistance and virulence, highlighting LptE function(s) as an interesting target to weaken P. aeruginosa defenses and reduce its infectivity.
Perilla Oil Supplementation Improves Hypertriglyceridemia and Gut Dysbiosis in Diabetic KKAy Mice

Scope The aim of this study is to examine whether perilla oil supplementation improves glucolipid metabolism and modulates gut microbiota in diabetic KKAy mice. Methods and results The successfully established diabetic KKAy mice are randomized into four groups: diabetic model (DM), low‐dose perilla oil (LPO), middle‐dose perilla oil (MPO), and high‐dose perilla oil (HPO). C57BL/6J mice are fed a chow diet as normal control (NC). At the end of 12 weeks, mice are euthanized and glucolipid indications are analyzed. Gut microbiota analysis is carried out based on the sequencing results on V4 region of 16S rRNA. Although serum glucose, insulin, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, abundance‐based coverage estimator, and shannon are unchanged, serum triglyceride significantly decreases in LPO compared with DM. The histopathological changes of hepatocellular macrovesicular steatosis and adipocyte hypertrophy are ameliorated by perilla oil supplementation. Blautia is significantly decreased in LPO, MPO, and HPO, compared with DM. Nonmetric multidimensional scaling analysis shows NC and LPO are relatively coherent. Conclusion These findings indicate that dietary supplementation with perilla oil can improve hypertriglyceridemia and gut dysbiosis in diabetic KKAy mice, which can be associated with potential benefits to human health.
Newly Identified Nucleoid-Associated-Like Protein YlxR Regulates Metabolic Gene Expression in Bacillus subtilis

Expression of genes encoding NAPs is often temporally regulated. According to results from single-cell analysis, the ylxR gene is induced by glucose and expressed in a bistable mode. These characteristics have not previously been reported for NAP gene expression. Transcriptional profiling of the ylxR disruptant revealed a change in the expression levels of approximately 400 genes, including genes for synthesis of 12 amino acids and 4 nucleotides, in addition to the SigX/M regulons. Thus, YlxR is a critical regulator of glucose response in B. subtilis. ABSTRACT Glucose is the most favorable carbon source for the majority of bacteria, which have several glucose-responsive gene networks. Recently, we found that in Bacillus subtilis, glucose induces expression of the extracellular sigma factor genes sigX/M. To explore the factors affecting this phenomenon, we performed a transposon mutagenesis screen for mutants with no glucose induction (GI) of sigX-lacZ and identified ylxR. YlxR is widely conserved in eubacteria. Further analysis revealed that ylxR is induced by glucose addition. In vitro DNA-binding and cytological studies suggested that YlxR is a nucleoid-associated protein (NAP) in B. subtilis. In many cases, NAPs influence transcription, recombination, and genome stability. Thus, we performed transcriptome sequencing (RNA-Seq) analysis to evaluate the impact of ylxR disruption on the transcriptome in the presence of glucose and observed that YlxR has a profound impact on metabolic gene expression in addition to that of four sigma factor genes. The wide fluctuations of gene expression may result in abolition of GI of sigX/M in the ylxR disruptant. IMPORTANCE Expression of genes encoding NAPs is often temporally regulated. According to results from single-cell analysis, the ylxR gene is induced by glucose and expressed in a bistable mode. These characteristics have not previously been reported for NAP gene expression. Transcriptional profiling of the ylxR disruptant revealed a change in the expression levels of approximately 400 genes, including genes for synthesis of 12 amino acids and 4 nucleotides, in addition to the SigX/M regulons. Thus, YlxR is a critical regulator of glucose response in B. subtilis.
A Framework for Evaluating Tablet-based Educational Applications for Primary School Levels in Thailand

When it comes to the use of mobile technology in the classroom, one of the major challenges for the teacher is finding suitable applications that appropriately match the topic of study. In most areas of education there are tools for evaluating teaching materials, but there are few tools for evaluating mobile technology in the classroom. The lack of evaluation methods means that for teachers, who are increasingly using tablets in the primary level classrooms, the results can be “hit or miss”. The aim of the study is to propose and describe a new framework that enables primary school teachers to evaluate tablet-based games effectively. The proposed framework is adapted from the four-dimensional framework (FDF). Thereby, supporting teachers in the choice of suitable tablet-based games to use in their classrooms that balance the essential aspects of student engagement (or playability) and learning achievement. A small case study is carried out based on the evaluation of 30 iPads STEM applications. The proposed framework can predict the initial pitfalls of technical and design issues in applications before class use. The successfully evaluated applications are used for the experiment at primary school in Thailand. The improvement of students’ learning skill, behavioral outcomes, and teachers’ perspectives are not considered in this study.
X-in-the-loop advanced driving simulation platform for the design,development, testing and validation of ADAS

This paper presents a X-in-the-loop (where X: Model, Software, Hardware, Driver/Human, etc.) driving simulation platform, developed at Siemens PLM Software, that facilitates the design, development, testing and validation of Advanced Driver Assistance System (ADAS). The paper outlines the essential components of the simulator and demonstrates the usefulness by two autonomous driving functionalities i.e. adaptive cruise control and autonomous intersection crossing. In addition, the paper highlights the key features of the platform.
Combined expression of protein disulfide isomerase and endoplasmic reticulum oxidoreductin 1-α is a poor prognostic marker for non-small cell lung cancer

Protein disulfide isomerase (PDI) is one of the most abundant proteins in the endoplasmic reticulum (ER) and is known as a primary ER resident target of cigarette smoke-induced oxidation. PDI dysfunction triggers unfolded protein response and ER stress. Endoplasmic reticulum oxidoreductin 1-α (ERO1A) is a major regulator of PDI, and recent evidence implicates PDI and ERO1A as tumor prognostic factors. However, the associated role of PDI and ERO1A and their prognostic impact in non-small cell lung cancers (NSCLCs) remains unknown. The present study investigated the expression of PDI and ERO1A using immunohistochemistry and examined its association with smoking status and their prognostic impact in 198 NSCLCs. PDI and ERO1A expression were observed in 71.2 and 69.2% of NSCLCs, respectively, and their expressions were significantly associated with each other (P<0.001). Individual PDI (P=0.001) and ERO1A (P=0.005) expression were significantly associated with shorter overall survival (OS) in univariate analysis. PDI expression was significantly associated with never smoking (P=0.003). PDI expression (P<0.001) and the co-expression of PDI and ERO1A (P<0.001) were independent poor prognostic factors for OS in patients with NSCLC in multivariate analysis. Individual expression and co-expression of PDI and ERO1A may be used as novel prognostic indicators of NSCLC outcome.
Barriers to a safety checklist and methods to improve usage of the WHO safety checklist in interventional radiology

Our aims were to first assess uptake of the modified safety checklist (SC) for interventional radiology (IR), identify obstacles to using the SC, and then apply changes to local policy to reach maximum compliance. Retrospective data collection was performed of all patients who underwent an interventional procedure in the interventional suite at the Royal Berkshire Hospital in February, March and May 2014. Barriers to a SC: a lack of awareness about the SC; lack of training in how to complete the SC; lack of leadership—no team member had been given the role of promoting the SC and collecting and collating the SC; attitude of staff—some team members felt that the SCs were time consuming and further bureaucracy; out-of-hours procedures involved staff from outside departments who were not familiar with the SC; paper copies of the completed SCs were being misplaced. Results: February 2014 = 79%; staff education of the importance of the modified World Health Organization (WHO) checklist disseminated in the interventional suite and at clinical governance; each day a designated ‘SC champion’ in the interventional suite has the responsibility for overseeing the WHO checklist is completed for each patient; the use of a clipboard for storing checklists, amalgamated and scored at the end of each day. Any checklists not completed are highlighted and discussed with the consultant. March 2014 = 95%; junior nurse involvement in auditing to improve awareness and engagement; out-of-hours interventional radiologist ensuring that the checklist is completed for each patient. May 2014 = 100%.