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Nasim Montazeri Ghahjaverestan,1,2 Sina Akbarian,1,2 Maziar Hafezi,1,2 Shumit Saha,1,2 Kaiyin Zhu,1 Bojan Gavrilovic,1 Babak Taati,1– 3,* Azadeh Yadollahi1,2,* 1Kite - Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada; 2Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; 3Computer Science, University of Toronto, Toronto, ON, Canada*These authors contributed equally to this workCorrespondence: Azadeh YadollahiKite - Toronto Rehabilitation Institute, University Health Network, Room 12-106, 550 University Avenue, Toronto, ON M5G 2A2, CanadaTel +1 416 597 3422 Ext 7936Fax +1 416 597 8959Email Azadeh.Yadollahi@uhn.caPurpose: The current gold standard to detect sleep/wakefulness is based on electroencephalogram, which is inconvenient if included in portable sleep screening devices. Therefore, a challenge in the portable devices is sleeping time estimation. Without sleeping time, sleep parameters such as apnea/hypopnea index (AHI), an index for quantifying sleep apnea severity, can be underestimated. Recent studies have used tracheal sounds and movements for sleep screening and calculating AHI without considering sleeping time. In this study, we investigated the detection of sleep/wakefulness states and estimation of sleep parameters using tracheal sounds and movements.Materials and Methods: Participants with suspected sleep apnea who were referred for sleep screening were included in this study. Simultaneously with polysomnography, tracheal sounds and movements were recorded with a small wearable device, called the Patch, attached over the trachea. Each 30-second epoch of tracheal data was scored as sleep or wakefulness using an automatic classification algorithm. The performance of the algorithm was compared to the sleep/wakefulness scored blindly based on the polysomnography.Results: Eighty-eight subjects were included in this study. The accuracy of sleep/wakefulness detection was 82.3± 8.66% with a sensitivity of 87.8± 10.8 % (sleep), specificity of 71.4± 18.5% (awake), F1 of 88.1± 9.3% and Cohen’s kappa of 0.54. The correlations between the estimated and polysomnography-based measures for total sleep time and sleep efficiency were 0.78 (p< 0.001) and 0.70 (p< 0.001), respectively.Conclusion: Sleep/wakefulness periods can be detected using tracheal sound and movements. The results of this study combined with our previous studies on screening sleep apnea with tracheal sounds provide strong evidence that respiratory sounds analysis can be used to develop robust, convenient and cost-effective portable devices for sleep apnea monitoring.Keywords: sleep apnea, apnea/hypopnea index, principal component analysis, classification, imbalanced data

Statement of Problem: Hemostatic agents may affect the micro-leakage of different adhesive systems. Also, chlorhexidine has shown positive effects on micro-leakage. However, their interaction effect has not been reported yet. Objectives: To evaluate the effect of contamination with a hemostatic agent on micro- leakage of total- and self-etching adhesive systems and the effect of chlorhexidine application after the removal of the hemostatic agent. Materials and Methods: Standardized Class V cavity was prepared on each of the sixty caries free premolars at the cemento-enamel junction, with the occlusal margin located in enamel and the gingival margin in dentin. Then, the specimens were randomly divided into 6 groups (n = 10) according to hemostatic agent (H) contamination, chlorhexidine (CHX) application, and the type of adhesive systems (Adper Single Bond and Clearfil SE Bond) used. After filling the cavities with resin composite, the root apices were sealed with utility wax. Furthermore, all the surfaces, except for the restorations and 1mm from the margins, were covered with two layers of nail varnish. The teeth were immersed in a 0.5% basic fuschin dye for 24 hours, rinsed, blot-dried and sectioned longitudinally through the center of the restorations bucco- lingualy. The sections were examined using a stereomicroscope and the extension of dye penetration was analyzed according to a non-parametric scale from 0 to 3. Statistical analysis was performed using Kruskal-Wallis test and Mann-Whitney U-test. Results: While ASB group showed no micro-leakage in enamel, none of the groups showed complete elimination of micro-leakage from the dentin. Regarding micro- leakage at enamel, and dentin margins, there was no significant difference between groups 1 and 2, 1 and 3, and 2 and 3 (p > 0.05). A significantly lower micro-leakage at the enamel and dentin margins was observed in group 3, compared to group 6. No significant difference was observed between groups 4 and 5 in enamel (p = 0.35) and dentin (p = 0.34). Group 6 showed significantly higher micro-leakage, compared to group 4 and 5 (p < 0.05). Conclusions: Hemostatic agent contamination had no significant effect on micro- leakage of total- and self-etching adhesive systems. Application of chlorhexidine after the removal of hemostatic agent increased micro-leakage in self-etching adhesives but did not affect when total-etching was used.

Lupus erythematosus (LE) is an autoimmune disease. The mortality rate and causes of death are different in various countries. The present study is done to find out the causes of mortality in the systemic lupus erythematosus (SLE) patients in lupus unit of Rheumatology Research Center and other wards of Shariati Hospital. This study was retrospective according to medical records of patients who were referred to Lupus Unit of Rheumatology Research center, ICU, Gynecology and Nephrology wards of Shariati hospital during 10 years, from 1991 till 2001. Of 2021-recorded patient’s files, 165 (7.8%) deaths were already recorded. 84.8% were female and 15.2% male. The duration of disease was 36±12 months. The mean duration of follow up from entering the study till time of death was 25.9±16.8 months. The causes of mortality were as follows: infection (12.1%), respiratory (8.5%), CNS (13.9%), kidney (3.6%), malignancy (1.2%), unknown (7.8%), active lupus (3%). Infection accompanied with other causes (27.9%) , respiratory with other causes (11.5%), CNS with other causes (5.5%) and renal with other causes (4.8%). Infections are the most common cause of death in SLE Iranian patients, which is compatible with some multicentric studies. But in some previous studies myocardial infarction was reported as the main cause of death.

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.

Sugarcane is a perennial crop that contributes to nearly 80% of the global sugar-based products. Therefore, sugarcane growers and food companies are seeking ways to address the concerns related to sugarcane crop yield and health. In this study, a spatial and spectral analysis on the peak growth stage of the sugarcane fields in Bundaberg, Queensland, Australia is performed using the Normalized Difference Vegetation Index (NDVI) and Normalized Difference Red Edge Index (NDRE) derived from high-resolution WorldView-2 (WV2) images and multispectral Unmanned Aerial Vehicle (UAV) images. Two topics are chosen for this study: 1) the difference and correlation between NDVI and NDRE that are commonly used to estimate Leaf Area Index, a common crop parameter for the assessment of crop yield and health stages; 2) the impact of spatial resolution on the systematic difference in the abovementioned two Vegetation Indices (VIs). The statistical correlation analysis between the WV2 and UAV images produced correlation coefficients of 0.68 and 0.71 for NDVI and NDRE, respectively. In addition, an overall comparison of the WV2 and UAV-derived VIs indicated that the UAV images produced a better accuracy than the WV2 images because UAV can effectively distinguish various status of vegetation owing to its high spatial resolution. The results illustrated a strong positive correlation between NDVI and NDRE, each derived from the WV2 and UAV images, and the correlation coefficients were 0.81 and 0.90, respectively, i.e. the correlation between NDVI and NDRE is higher in the UAV images than the WV2 images. [ABSTRACT FROM AUTHOR]

Abstract Background DNA-protein interactions in mature brain are increasingly recognized as key regulators for behavioral plasticity and neuronal dysfunction in chronic neuropsychiatric disease. However, chromatin assays typically lack single cell resolution, and therefore little is known about chromatin regulation of differentiated neuronal nuclei that reside in brain parenchyma intermingled with various types of non-neuronal cells. Results Here, we describe a protocol to selectively tag neuronal nuclei from adult brain – either by (anti-NeuN) immunolabeling or transgene-derived histone H2B-GFP fusion protein – for subsequent fluorescence-activated sorting and chromatin immunoprecipitation (ChIP). To illustrate an example, we compared histone H3 lysine 4 and 9 methylation marks at select gene promoters in neuronal, non-neuronal and unsorted chromatin from mouse forebrain and human cerebral cortex, and provide evidence for neuron-specific histone methylation signatures. Conclusion With the modifications detailed in this protocol, the method can be used to collect nuclei from specific subtypes of neurons from any brain region for subsequent ChIP with native/un-fixed or crosslinked chromatin preparations. Starting with the harvest of brain tissue, ChIP-ready neuronal nuclei can be obtained within one day.

We apply a single-molecule chromatin fiber sequencing (Fiber-seq) protocol designed for amplification-free cell-type-specific mapping of the regulatory architecture at nucleosome resolution along extended ∼10-kb chromatin fibers to neuronal and non-neuronal nuclei sorted from human brain tissue. Specifically, application of this method enables the resolution of cell-selective promoter and enhancer architectures on single fibers, including transcription factor footprinting and position mapping, with sequence-specific fixation of nucleosome arrays flanking transcription start sites and regulatory motifs. We uncover haplotype-specific chromatin patterns, multiple regulatory elements cis-aligned on individual fibers, and accessible chromatin at 20,000 unique sites encompassing retrotransposons and other repeat sequences hitherto "unmappable" by short-read epigenomic sequencing. Overall, we show that Fiber-seq is applicable to human brain tissue, offering sharp demarcation of nucleosome-depleted regions at sites of open chromatin in conjunction with multi-kilobase nucleosomal positioning at single-fiber resolution on a genome-wide scale., Competing Interests: Declaration of interests A.B.S. is a co-inventor on a patent relating to the Fiber-seq method (US17/995,058)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sleeping on the back after 28 weeks of pregnancy has recently been associated with giving birth to a small-for-gestational-age infant and late stillbirth, but whether a causal relationship exists is currently unknown and difficult to study prospectively. This study was conducted to build a computer vision model that can automatically detect sleeping position in pregnancy under real-world conditions. Real-world overnight video recordings were collected from an ongoing, Canada-wide, prospective, four-night, home sleep apnea study and controlled-setting video recordings were used from a previous study. Images were extracted from the videos and body positions were annotated. Five-fold cross validation was used to train, validate, and test a model using state-of-the-art deep convolutional neural networks. The dataset contained 39 pregnant participants, 13 bed partners, 12,930 images, and 47,001 annotations. The model was trained to detect pillows, twelve sleeping positions, and a sitting position in both the pregnant person and their bed partner simultaneously. The model significantly outperformed a previous similar model for the three most commonly occurring natural sleeping positions in pregnant and non-pregnant adults, with an 82-to-89% average probability of correctly detecting them and a 15-to-19% chance of failing to detect them when any one of them is present., (© 2024. The Author(s).)

Background: To describe the implementation of a registry system for patients with thyroid eye disease (TED) in Iran to obtain more information about its nature, prevalence, and annual incidence, as well as extend insight into the etiology, pathogenesis, and eventually make an accurate prognosis of different medical or surgical treatment methods., Methods: After receiving approval from the Disease Registry Committee of Iran University of Medical Sciences (IUMS) in 2019 and the Ministry of Health and Medical Education (MOHME) in 2020, the protocol was introduced in three consecutive phases at regional, provincial and national levels. The establishment of a registry committee in Rassoul Akram Hospital, one of the medical centers affiliated to IUMS, was the first step to organizing the registry project's main core. The steering committee included six subgroups of required subject fields. The members are experts in developing a guideline, providing a new dataset, drawing an outline for the next steps, and structuring user-friendly software through several panel discussion meetings. The data is collected from clinical and para-clinical/imaging findings, laboratory evaluations, and their selected treatment strategy, retrospectively and prospectively., Results: The purpose is to broaden our knowledge about the profile of TED; accordingly, data related to patients' demographics, thyroid gland disease (status, duration, treatments, and function tests), general medical and ocular history, along with visual/ocular exams resulting TED status are collected and recorded in a 2- language software. The web-based software system is accessible at https://orc.iums.ac.ir . To maintain data security, prioritized user access was defined for different members. Furthermore, diverse methods, such as employing trained staff and utilizing software validation rules, were implemented to control data quality in every step of data collection, entry, and registration. Medical records of retrospective subjects were also evaluated and entered after accuracy verification., Conclusion: Iran's TED registry provides practitioners with comprehensive data on natural history and phenotype variations in clinical features and outcomes. It facilitates patient recruitment and, consequently, earlier diagnosis on a large scale which helps improve treatment and quality of life for patients., (© 2024. The Author(s).)

Importance: Our mouse model is a powerful tool for investigating the genetic mechanisms governing central nervous system (CNS) human immunodeficiency virus type-1 (HIV-1) infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses induced pluripotent stem cell-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be explored in vivo , which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency., Competing Interests: The authors declare no conflict of interest.

Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here., (© 2023. The Author(s).)

In 2021, the National Guideline Alliance for the Royal College of Obstetricians and Gynaecologists reviewed the body of evidence, including two meta-analyses, implicating supine sleeping position as a risk factor for growth restriction and stillbirth. While they concluded that pregnant people should be advised to avoid going to sleep on their back after 28 weeks' gestation, their main critique of the evidence was that, to date, all studies were retrospective and sleeping position was not objectively measured. As such, the Alliance noted that it would not be possible to prospectively study the associations between sleeping position and adverse pregnancy outcomes. Our aim was to demonstrate the feasibility of building a vision-based model for automated and accurate detection and quantification of sleeping position throughout the third trimester-a model with the eventual goal to be developed further and used by researchers as a tool to enable them to either confirm or disprove the aforementioned associations. We completed a Canada-wide, cross-sectional study in 24 participants in the third trimester. Infrared videos of eleven simulated sleeping positions unique to pregnancy and a sitting position both with and without bed sheets covering the body were prospectively collected. We extracted 152,618 images from 48 videos, semi-randomly down-sampled and annotated 5,970 of them, and fed them into a deep learning algorithm, which trained and validated six models via six-fold cross-validation. The performance of the models was evaluated using an unseen testing set. The models detected the twelve positions, with and without bed sheets covering the body, achieving an average precision of 0.72 and 0.83, respectively, and an average recall ("sensitivity") of 0.67 and 0.76, respectively. For the supine class with and without bed sheets covering the body, the models achieved an average precision of 0.61 and 0.75, respectively, and an average recall of 0.74 and 0.81, respectively., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AJK is the volunteer (unpaid) Chief Executive Officer and President of one of the study funders, Shiphrah Biomedical Inc. (SBI). AJK did not receive financial or material payment for his involvement in this study. EP is a volunteer at SBI and a shareholder in SBI. EP received a financial payment for her involvement in this study from the study funds. HH was involved in this work via an internship as part of his graduate studies at the University of Toronto. HH received a financial payment for his internship from the study funds. HH has no role in ownership, management, or control of SBI. RS, HZ, FR, SA, BT, SRH, and ED have no competing interests that could be perceived to bias this work., (Copyright: © 2023 Kember et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain's reward circuitry., (© 2023. Springer Nature Limited.)

The SARS-CoV-2 pandemic persists with global repercussions. Initial COVID-19 symptoms encompass pneumonia, fever, myalgia, and fatigue. The human immune system produces IgM and IgG antibodies in response to SARS-CoV-2. Despite previous research, a comprehensive understanding of the interplay between clinical manifestations and humoral immune responses remains elusive. This study aims to scrutinize this association. 134 COVID-19 patients were enrolled, and stratified into mild, moderate, and severe symptom groups. Serum IgM and IgG levels were assessed thrice at one-month intervals using ELISA. The findings reveal significant elevation in serum IgG levels in moderate compared to mild cases ( P < 0.001). Additionally, IgG production was significantly heightened in severe cases compared to both mild ( P < 0.0001) and moderate ( P < 0.05) groups. IgM and IgG levels peaked initially and diminished over time. While anti-SARS-CoV-2 antibodies are expected to confer protection, the direct correlation between IgG levels and symptom severity may arise from delayed immune activation, resulting in an intense antibody response in severe cases. Given evidence linking delayed immune function with a dysregulated innate immune response, comprehensive data collection should encompass not only serum IgG and IgM, but also early measurement of type I interferons at symptom onset. This could provide a more thorough understanding of COVID-19 progression.

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)-present in some but not all cells-remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e-4), with recurrent somatic deletions of exons 1-5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis -regulatory elements upon 5' deletions in NRXN1 . We also observed recurrent intragenic deletions of ABCB11 , encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified in the brain, and their functional roles in the brain are not clear. Here we show paternal, but not maternal, expression of MIR125B2 in human but not mouse brain. Moreover, Mir125b-2 m - /p - mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2 m - /p - mice displayed increased neuronal excitability, increased excitatory synaptic transmission, and decreased inhibitory synaptic transmission. Glutamate ionotropic receptor NMDA type subunit 2A (Grin2a), a key regulator of synaptic plasticity, was physically bound by miR-125b-2 and upregulated in the hippocampus of Mir125b-2 m - /p - mice. Taken together, our findings demonstrate MIR125B2 imprinted in human but not mouse brain, mediated learning, memory, and anxiety, regulated excitability and synaptic transmission in hippocampal granule cells, and affected hippocampal expression of Grin2a. Our work provides functional mechanisms of a species-specific imprinted microRNA in the brain., (© 2023. The Author(s).)

To explore genome organization and function in the HIV-infected brain, we applied single-nuclei transcriptomics, cell-type-specific chromosomal conformation mapping, and viral integration site sequencing (IS-seq) to frontal cortex from individuals with encephalitis (HIVE) and without (HIV+). Derepressive changes in 3D genomic compartment structures in HIVE microglia were linked to the transcriptional activation of interferon (IFN) signaling and cell migratory pathways, while transcriptional downregulation and repressive compartmentalization of neuronal health and signaling genes occurred in both HIVE and HIV+ microglia. IS-seq recovered 1,221 brain integration sites showing distinct genomic patterns compared with peripheral lymphocytes, with enrichment for sequences newly mobilized into a permissive chromatin environment after infection. Viral transcription occurred in a subset of highly activated microglia comprising 0.33% of all nuclei in HIVE brain. Our findings point to disrupted microglia-neuronal interactions in HIV and link retroviral integration to remodeling of the microglial 3D genome during infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Non-random spatial organization of the chromosomal material inside the nuclei of brain cells emerges as an important regulatory layer of genome organization and function in health and disease. Here, we discuss how integrative approaches assessing chromatin in context of the 3D genome is providing new insights into normal and diseased neurodevelopment. Studies in primate (incl. human) and rodent brain have confirmed that chromosomal organization in neurons and glia undergoes highly dynamic changes during pre- and early postnatal development, with potential for plasticity across a much wider age window. For example, neuronal 3D genomes from juvenile and adult cerebral cortex and hippocampus undergo chromosomal conformation changes at hundreds of loci in the context of learning and environmental enrichment, viral infection, and neuroinflammation. Furthermore, locus-specific structural DNA variations, such as micro-deletions, duplications, repeat expansions, and retroelement insertions carry the potential to disrupt the broader epigenomic and transcriptional landscape far beyond the boundaries of the site-specific variation, highlighting the critical importance of long-range intra- and inter-chromosomal contacts for neuronal and glial function.

The pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN-), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN-) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy., (© 2022. The Author(s).)

The excitation-emission fluorescence spectroscopy combined with three-way analysis was applied for discriminating the pure BSA and BSA/Fe 3 O(OAc) 6 ClO 4 (Fe) using unsupervised classification methods. Herein, the interaction of bovine serum albumin (BSA) and Fe clusters as an artificial enzyme is studied by extracting the intrinsic excitation-emission (EEM) fluorescence of BSA. The conformation of BSA changes with pH, temperature, and Fe concentration. Three-way fluorescence data were recorded for BSA and BSA/Fe during different days. The obtained results showed that the Fe clusters cause changes in the structure of BSA conformation as a function of pH, temperature, and Fe concentration. Also, the denaturation pathway of the BSA molecule is significantly different in the presence of Fe clusters. Both techniques of PARAFAC and PCA were used in the excitation-emission fluorescence matrices (EEM) of solutions at three different pH (5.0, 7.0, and 9.0) and temperatures (15.0, 25.0, and 35.0 °C) values. Also, we reported the results of the change in concentrations of Fe (4.0, 6.0, and 8.0 mg) using these methods. These three amino acids (tyrosine, tryptophan, and phenylalanine) indicate all datasets and their similarities and differences. The spectral differences were more remarkable in different pH values compared to different temperatures. Also, we could distinguish between the groups of protein samples properly in different concentrations of Fe using low-cost EEM spectral images and PARAFAC., (© 2022. The Author(s).)

RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons., (© The Author(s) 2022. Published by Oxford University Press.)

Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways., (© 2022. The Author(s).)

Background: The growing prevalence of depression has become a major public health problem. There is limited evidence regarding the relationship between dietary behaviors and depression. The present study was designed to evaluate the association between dietary behaviors and depression score., Methods: A total of 933 Iranian adolescent girls aged 12 to 18 years were included in this cross-sectional study. Depression severity score was assessed using a validated Persian version of Beck's depression inventory. Dietary behaviors were pre-defined and assessed in ten domains using a standard questionnaire. To investigate the association between dietary behaviors and depression score, the linear regression analysis in crude and adjusted models was used., Results: 67.7% of participants had no or minimal depression symptoms and 32.3% of participants were categorized with mild-to-severe depression symptoms. There were significant inverse relationships between main meal consumption (Beta: -0.141; 95% CI: - 3.644 to - 1.000; P = 0.001), snack consumption (Beta: -0.100; 95% CI: - 2.400 to - 0.317; P = 0.002), regular meal consumption (Beta: 0.23; 95% CI: 0.13-0.42; P = 0.001) and food chewing (Beta: -0.152; 95% CI: - 2.279 to - 0.753; P = 0.03) with depression score. These associations remained significant after adjustment for confounding variables. In addition, frequency of intra-meal fluid intake (Beta: 0.096; 95% CI: 0.288 to 1.535; P = 0.004) and spicy foods consumption (Beta: 0.076; 95% CI: 0.098 to 1.508; P = 0.02) were directly associated with depression score in the crude model. These significant relations were disappeared in full adjusted model. No significant association was found between breakfast consumption, intake of fried foods, chewing ability, and tooth loss with depression score (P > 0.05)., Conclusions: Significant associations were observed between specific eating behaviors with depression score. Prospective studies are needed to confirm these findings., (© 2022. The Author(s).)

Purpose: To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED)., Methods: A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including in vitro ) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of H 2 O 2 -dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the in vitro studies., Results: Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 in vitro studies from 1993 to 2018. While β-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in in vitro studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial., Conclusion: While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Current Ophthalmology.)

Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associated receptor (PPAR) signaling regulates glycolysis and fatty acid oxidation (FAO) in an isoform-specific manner. While PPARalpha (PPARa) is the most active isoform in hPSC-CMs, PPARdelta (PPARd) activation efficiently upregulates the gene regulatory networks underlying FAO, increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation, and augments FAO flux. PPARd activation further increases binucleation, enhances myofibril organization, and improves contractility. Transient lactate exposure, which is frequently used for hPSC-CM purification, induces an independent cardiac maturation program but, when combined with PPARd activation, still enhances oxidative metabolism. In summary, we investigate multiple metabolic modifications in hPSC-CMs and identify a role for PPARd signaling in inducing the metabolic switch from glycolysis to FAO in hPSC-CMs., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Lyme disease (caused by Borrelia burgdorferi ) is an infectious disease transmitted to humans by a bite from infected blacklegged ticks ( Ixodes scapularis ) in eastern North America. Lyme disease can be prevented if antibiotic prophylaxis is given to a patient within 72 hours of a blacklegged tick bite. Therefore, recognizing a blacklegged tick could facilitate the management of Lyme disease. Methods: In this work, we build an automated detection tool that can differentiate blacklegged ticks from other tick species using advanced computer vision approaches in real-time. Specially, we use convolution neural network models, trained end-to-end, to classify tick species. Also, advanced knowledge transfer techniques are adopted to improve the performance of convolution neural network models. Results: Our best convolution neural network model achieves 92% accuracy on unseen tick species. Conclusion: Our proposed vision-based approach simplifies tick identification and contributes to the emerging work on public health surveillance of ticks and tick-borne diseases. In addition, it can be integrated with the geography of exposure and potentially be leveraged to inform the risk of Lyme disease infection. This is the first report of using deep learning technologies to classify ticks, providing the basis for automation of tick surveillance, and advancing tick-borne disease ecology and risk management.

Regulatory mechanisms associated with repeat-rich sequences and chromosomal conformations in mature neurons remain unexplored. Here, we map cell-type specific chromatin domain organization in adult mouse cerebral cortex and report strong enrichment of Endogenous Retrovirus 2 (ERV2) repeat sequences in the neuron-specific heterochromatic B 2 NeuN+ megabase-scaling subcompartment. Single molecule long-read sequencing and comparative Hi-C chromosomal contact mapping in wild-derived SPRET/EiJ (Mus spretus) and laboratory inbred C57BL/6J (Mus musculus) reveal neuronal reconfigurations tracking recent ERV2 expansions in the murine germline, with significantly higher B 2 NeuN+ contact frequencies at sites with ongoing insertions in Mus musculus. Neuronal ablation of the retrotransposon silencer Kmt1e/Setdb1 triggers B 2 NeuN+ disintegration and rewiring with open chromatin domains enriched for cellular stress response genes, along with severe neuroinflammation and proviral assembly with infiltration of dendrites . We conclude that neuronal megabase-scale chromosomal architectures include an evolutionarily adaptive heterochromatic organization which, upon perturbation, results in transcriptional dysregulation and unleashes ERV2 proviruses with strong neuronal tropism., (© 2021. The Author(s).)

Background: Sleep apnea is a respiratory disorder characterized by frequent breathing cessation during sleep. Sleep apnea severity is determined by the apnea-hypopnea index (AHI), which is the hourly rate of respiratory events. In positional sleep apnea, the AHI is higher in the supine sleeping position than it is in other sleeping positions. Positional therapy is a behavioral strategy (eg, wearing an item to encourage sleeping toward the lateral position) to treat positional apnea. The gold standard of diagnosing sleep apnea and whether or not it is positional is polysomnography; however, this test is inconvenient, expensive, and has a long waiting list., Objective: The objective of this study was to develop and evaluate a noncontact method to estimate sleep apnea severity and to distinguish positional versus nonpositional sleep apnea., Methods: A noncontact deep-learning algorithm was developed to analyze infrared video of sleep for estimating AHI and to distinguish patients with positional vs nonpositional sleep apnea. Specifically, a 3D convolutional neural network (CNN) architecture was used to process movements extracted by optical flow to detect respiratory events. Positional sleep apnea patients were subsequently identified by combining the AHI information provided by the 3D-CNN model with the sleeping position (supine vs lateral) detected via a previously developed CNN model., Results: The algorithm was validated on data of 41 participants, including 26 men and 15 women with a mean age of 53 (SD 13) years, BMI of 30 (SD 7), AHI of 27 (SD 31) events/hour, and sleep duration of 5 (SD 1) hours; 20 participants had positional sleep apnea, 15 participants had nonpositional sleep apnea, and the positional status could not be discriminated for the remaining 6 participants. AHI values estimated by the 3D-CNN model correlated strongly and significantly with the gold standard (Spearman correlation coefficient 0.79, P<.001). Individuals with positional sleep apnea (based on an AHI threshold of 15) were identified with 83% accuracy and an F1-score of 86%., Conclusions: This study demonstrates the possibility of using a camera-based method for developing an accessible and easy-to-use device for screening sleep apnea at home, which can be provided in the form of a tablet or smartphone app., (©Sina Akbarian, Nasim Montazeri Ghahjaverestan, Azadeh Yadollahi, Babak Taati. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.11.2021.)

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases., Methods: Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of the virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering > 99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain., Results: Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes, and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory, and gene regulatory network analyses revealed transcriptional changes in the cortical microglia associated with a range of biological processes, including cellular activation, mobility, and phagocytosis., Conclusions: Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19., (© 2021. The Author(s).)