A Pilot Randomized Controlled Trial Among People Recovering from Mental Illness: A Tailored Mindfulness-Based Intervention versus Relaxation Training.

BACKGROUND: This study assessed the potential effectiveness, acceptability and feasibility of a tailored mindfulness-based intervention (MBI, REMIND 2.0) for personal recovery among people with mental illness during the COVID-19 pandemic. METHODS: In this pilot mixed methods randomized controlled trial, participants were assigned to either the MBI (n = 14) or the relaxation training (RT) (n = 14). Quantitative measures were used to assess primary outcomes, including personal recovery, mindfulness, self-compassion, resilience, and secondary outcomes, including depression, stress, anxiety, positive and negative moods, quality of life and general health at baseline (T0), post-intervention (T1) and one-month follow-up (T2). Quantitative interviews were conducted to explore the experiences and perceptions toward the MBI. RESULTS: Results indicated significant group and time interactions for all outcomes except anxiety and stress. MBI participants showed significant improvements in all outcomes at T1, which were maintained at T2, except for positive mood. RT participants showed a significant decline in resilience but significant improvements in all secondary outcomes at T1, but all outcomes significantly declined at T2, except for anxiety and stress. MBI participants were receptive toward the programme in all aspects of personal recovery. CONCLUSIONS: The tailored MBI is a potentially effective, feasible and acceptable approach to facilitate personal recovery among people with mental illness. Differences between MBI and RT are discussed.

Remote neuronal activity drives glioma progression through SEMA4F.

The tumour microenvironment plays an essential role in malignancy, and neurons have emerged as a key component of the tumour microenvironment that promotes tumourigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bidirectional signalling between tumours and neurons that propagates a vicious cycle of proliferation, synaptic integration and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumour subpopulations driving this phenomenon is incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumours promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity-dependent infiltrating population present at the leading edge of mouse and human tumours that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression. Furthermore, SEMA4F promotes the activity-dependent infiltrating population and propagates bidirectional signalling with neurons by remodelling tumour-adjacent synapses towards brain network hyperactivity. Collectively our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, and also show new mechanisms of glioma progression that are regulated by neuronal activity.

Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation.

Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional up-regulation and down-regulation in astrocytes, highlighted by the identification of Slc22a3 as an activity-inducible astrocyte gene that encodes neuromodulator transporter Slc22a3 and regulates sensory processing in the mouse olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduced the expression of γ-aminobutyric acid (GABA) biosynthetic genes and GABA release, culminating in olfactory deficits. Our study reveals that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.

Effects of acute moderate-intensity exercise on executive function in children with preterm birth: A randomized crossover study.

BACKGROUND: Acute exercise appears to promote executive function (EF) in children. However, the effect of acute exercise on EF in children with preterm birth (PB) remains unclear. OBJECTIVE: To investigate whether acute moderate-intensity exercise improves EF in children with PB. METHODS: Twenty child participants with PB (age = 10.95 ± 1.19 years, birth age = 31.71 ± 3.64 weeks) completed exercise and control sessions in a randomized crossover design. In the exercise session, participants completed a 30-minute period of moderate-intensity aerobic exercise. In the control session, participants watched a video for appropriately 30 min. Following each session immediately, inhibitory control, an aspect of EF, was assessed with the Numerical Stroop task. RESULTS: Response time (RT) for the Stroop's incongruent condition was shorter after the exercise session than after the control session. However, no differences were observed in RT for the congruent condition. Accuracy rate (ACC) in both congruent and incongruent conditions did not differ between exercise and control session. CONCLUSION: The findings support the beneficial effect of acute exercise on executive function (EF) in children with PB, particularly in terms of improving inhibitory control.

Inhibitory input directs astrocyte morphogenesis through glial GABABR.

Communication between neurons and glia has an important role in establishing and maintaining higher-order brain function1. Astrocytes are endowed with complex morphologies, placing their peripheral processes in close proximity to neuronal synapses and directly contributing to their regulation of brain circuits2-4. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation5-7; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unclear. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABAB receptor (GABABR) and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together, our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation.

Neuronal activity drives global alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. Here we show that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduces serotonin levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduces expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study reveals that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes, while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.

Inhibitory input directs astrocyte morphogenesis through glial GABA B R.

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABA B R and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABA B R in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABA B R as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

Remote neuronal activity drives glioma infiltration via Sema4f.

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity dependent infiltrating population present at the leading edge of mouse and human tumors that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified Sema4F as a key regulator of tumorigenesis and activity-dependent infiltration. Furthermore, Sema4F promotes the activity-dependent infiltrating population and propagates bi-directional signaling with neurons by remodeling tumor adjacent synapses towards brain network hyperactivity. Collectively, our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, while revealing new mechanisms of tumor infiltration that are regulated by neuronal activity.

Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits.

Social experience is essential for the development and maintenance of higher-order brain function. Social deprivation results in a host of cognitive deficits, and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown. Here, we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression. We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation. Mechanistically, TRPA1 inhibition of hippocampal circuits is mediated by a parallel increase of astrocytic production and release of the inhibitory neurotransmitter GABA after social deprivation. Collectively, our studies reveal how astrocyte function is tuned to social experience and identifies a social-context-specific mechanism by which astrocytic TRPA1 and GABA coordinately suppress hippocampal circuit function.

Sculpting Astrocyte Diversity through Circuits and Transcription.

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the lens of brain region-specific circuits. We articulate our understanding of how transcriptional mechanisms regulate this diversity and key areas that need further exploration to achieve the overarching goal of a functional taxonomy of astrocytes in the brain.

Passive sampling hypothesis did not shape microbial species-area relationships in open microcosm systems.

The passive sampling hypothesis is one of the most important hypotheses used to explain the mechanism of species-area relationships (SAR) formation. This hypothesis has not yet been experimentally validated due to the confusion between passive sampling (a larger area may support more colonists when fully sampled) and sampling effects (more sampling effort will result in increased species richness when sampling is partial). In this study, we created an open microcosm system with homogeneous habitat, consistent total resources, and biodiversity background using Chinese paocai soup, a fermented vegetable, as a substrate. We made efforts to entirely exclude the influence of sampling effects and to exclusively obtain microorganisms from dispersal using microcosm and high-throughput sequencing techniques. However, in this study, passive sampling based on dispersal failed to shape SAR, and community differences were predominantly caused by species replacement, with only minor contributions from richness differences. Ecological processes including extinction and competitive exclusion, as well as underlying factors like temporal scales and the small island effects, are very likely to have been involved in the studied system. To elucidate the mechanism of SAR development, future studies should design experiments to validate the involvement of dispersal independently.

Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer.

Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A-dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non-small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.

Measuring Roadway Lane Widths Using Connected Vehicle Sensor Data.

The United States has over three trillion vehicle miles of travel annually on over four million miles of public roadways, which require regular maintenance. To maintain and improve these facilities, agencies often temporarily close lanes, reconfigure lane geometry, or completely close the road depending on the scope of the construction project. Lane widths of less than 11 feet in construction zones can impact highway capacity and crash rates. Crash data can be used to identify locations where the road geometry could be improved. However, this is a manual process that does not scale well. This paper describes findings for using data from onboard sensors in production vehicles for measuring lane widths. Over 200 miles of roadway on US-52, US-41, and I-65 in Indiana were measured using vehicle sensor data and compared with mobile LiDAR point clouds as ground truth and had a root mean square error of approximately 0.24 feet. The novelty of these results is that vehicle sensors can identify when work zones use lane widths substantially narrower than the 11 foot standard at a network level and can be used to aid in the inspection and verification of construction specification conformity. This information would contribute to the construction inspection performed by agencies in a safer, more efficient way.

Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis.

AIMS: Diabetes is associated with increased risk of fracture. This study aims to evaluate the correlation between anti-diabetic agents and fracture risk in patients with type 2 diabetes. METHODS: Literature research was conducted using PubMed, Embase, and ClinicalTrials.gov. Search-term included "type 2 diabetes," "fracture," "randomized controlled trial," and seven kinds of anti-diabetic agents. Random-effect models established fractures in the follow-up period as the primary outcome. A network meta-analysis was performed to compare available treatments within a single Bayesian analytical framework. RESULTS: A total of 191,361 patients were included in 161 studies, with 2916 fractures. DPP-4i (risk ratio [RR] 1.76 [95 % confidence interval (CI) 1.21-2.55]), SGLT-2i (RR 1.5 [95 % CI 1.05-2.16]) and placebo (RR 1.44 [95 % CI 1.04-1.98]) increased fracture risk when compared to GLP1-RA. GLP1-RA (RR 0.5 [95 % CI 0.31-0.79]) and SU (RR 0.56 [95 % CI 0.41-0.77]) provided greater protection against fracture than TZD. DPP-4i increased fracture risk when compared to SU (RR 1.55 [95 % CI 1.08-2.22]), and was comparable in effect to TZD. CONCLUSIONS: GLP1-RA offered better protection against fracture than placebo. Insulin and SU had effects comparable with GLP1-RA. SU offered greater protection against fractures than TZD and DPP-4i. SGLT-2i increased risk of fracture when compared to GLP1-RA.

A Synchrotron Radiation Photoemission Study of SiGe(001)-2×1 Grown on Ge and Si Substrates: The Surface Electronic Structure for Various Ge Concentrations.

Beyond the macroscopic perspective, this study microscopically investigates Si1-xGex(001)-2×1 samples that were grown on the epi Ge(001) and epi Si(001) substrates via molecular-beam epitaxy, using the high-resolution synchrotron radiation photoelectron spectroscopy (SRPES) as a probe. The low-energy electron diffraction equipped in the SRPES chamber showed 2×1 double-domain reconstruction. Analyses of the Ge 3d core-level spectra acquired using different photon energies and emission angles consistently reveal the ordered spots to be in a Ge-Ge tilted configuration, which is similar to that in epi Ge(001)-2×1. It was further found that the subsurface layer was actually dominated by Ge, which supported the buckled configuration. The Si atoms were first found in the third surface layer. These Si atoms were further divided into two parts, one underneath the Ge-Ge dimer and one between the dimer row. The distinct energy positions of the Si 2p core-level spectrum were caused by stresses, not by charge alternations.

Kawasaki Shock Syndrome with Initial Presentation as Neck lymphadenitis: A Case Report.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause that mainly affects infants and children and can result in coronary artery complications if left untreated. A small subset of KD patients with fever and cervical lymphadenitis has been reported as node-first-presenting KD (NFKD). This type of KD commonly affects the older pediatric population with a more intense inflammatory process. Considering its unusual initial presentation, a delay in diagnosis and treatment increases the risk of coronary artery complications. Herein, we report the case of a 9-year-old female with fever and neck mass that rapidly deteriorated to shock status. A diagnosis of KD was made after the signs and symptoms fulfilled the principal diagnostic criteria. The patient's heart failure and blood pressure improved dramatically after a single dose of intravenous immunoglobulin. This case reminds us that NFKD could be the initial manifestation of KDSS, which is a potentially fatal condition. We review the literature to identify the overlapping characteristics of NFKD and KDSS, and to highlight the importance of early recognition of atypical KD regardless of age. We conclude that unusually high C-reactive protein, neutrophilia, and thrombocytopenia serve as supplemental laboratory indicators for early identification of KDSS in patients with NFKD.

[Recent Developments and Future Directions of Oral Healthcare System and Dental Public Health System in China in Light of the Current Global Emergency].

The study is aimed to help promote the development of the oral healthcare system and dental public health system in China and to help achieve the goal of improving the nation's oral health. We herein provided an overview and critical evaluation of recent developments in oral healthcare systems and dental public health systems in China and other countries, and discussed a number of potential directions for the future development of dental public health. The current global public health emergency of the coronavirus disease 2019 (COVID-19) pandemic was also taken into account in our discussions. Thus, to facilitate the accomplishment of the goals of the Healthy China 2030 Program, we suggested the establishment of a community-based, prevention-oriented model for the oral healthcare system and dental public health system. The model we proposed features the integration of oral and general health services, the utilization of technological innovations and big data concerning health, and a forceful promotion of remote dental services focused on prevention and early diagnosis and treatment. Furthermore, under the background of COVID-19 becoming a normal part of people's lives, we should adopt differentiated prevention and protection measures and emergency response preplans appropriate for the actual epidemic situation of a particular region so that clinical services are strengthened while unnecessary wastes of resources are avoided. We should actively explore for alternative approaches to care in the face of special circumstances.

The clinical relevance of anti-glutamic acid decarboxylase antibodies in children with encephalitis/encephalopathy.

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy.

Processing Strategy and Comparative Performance of Different Mobile LiDAR System Grades for Bridge Monitoring: A Case Study.

Collecting precise as-built data is essential for tracking construction progress. Three-dimensional models generated from such data capture the as-is conditions of the structures, providing valuable information for monitoring existing infrastructure over time. As-built data can be acquired using a wide range of remote sensing technologies, among which mobile LiDAR is gaining increasing attention due to its ability to collect high-resolution data over a relatively large area in a short time. The quality of mobile LiDAR data depends not only on the grade of onboard LiDAR scanners but also on the accuracy of direct georeferencing information and system calibration. Consequently, millimeter-level accuracy is difficult to achieve. In this study, the performance of mapping-grade and surveying-grade mobile LiDAR systems for bridge monitoring is evaluated against static laser scanners. Field surveys were conducted over a concrete bridge where grinding was required to achieve desired smoothness. A semi-automated, feature-based fine registration strategy is proposed to compensate for the impact of georeferencing and system calibration errors on mobile LiDAR data. Bridge deck thickness is evaluated using surface segments to minimize the impact of inherent noise in the point cloud. The results show that the two grades of mobile LiDAR delivered thickness estimates that are in agreement with those derived from static laser scanning in the 1 cm range. The mobile LiDAR data acquisition took roughly five minutes without having a significant impact on traffic, while the static laser scanning required more than three hours.

Olfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain.

The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear. Here, we show that loss of the transcription factor Sox9 results in both anatomical and functional changes in adult mouse olfactory bulb (OB) astrocytes, affecting sensory processing. Indeed, astrocyte-specific deletion of Sox9 in the OB results in decreased odor detection thresholds and discrimination and it is associated with aberrant neuronal sensory response maps. At functional level, loss of astrocytic Sox9 impairs the electrophysiological properties of mitral and tufted neurons. RNA-sequencing analysis reveals widespread changes in the gene expression profiles of OB astrocytes. In particular, we observe reduced GLT-1 expression and consequential alterations in glutamate transport. Our findings reveal that astrocytes are required for physiological sensory processing and we identify astrocytic Sox9 as an essential transcriptional regulator of mature astrocyte function in the mouse OB.