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The repressor element 1 silencing transcription factor (REST) has been proposed to function as a transcription factor to silence gene transcription by binding to repressor element 1 (RE1), a highly conserved DNA motif. The functions of REST in various tumors have been studied, but its role and correlation with immune cell infiltration remains uncertain in gliomas. REST expression was analyzed in datasets of The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) and validated by the Gene Expression Omnibus and Human Protein Atlas databases. The clinical prognosis of REST was evaluated by clinical survival data of TCGA cohort and validated by Chinese Glioma Genome Atlas cohort. MicroRNAs (miRNAs) contributing to REST overexpression in glioma were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. The correlations between immune cell infiltration level and REST expression were analyzed by TIMER2 and GEPIA2 tools. Enrichment analysis of REST was performed using STRING and Metascape tools. The expression and function of predicted upstream miRNAs at REST and their association with glioma malignancy and migration were also confirmed in glioma cell lines. REST was highly expressed and associated with poorer overall survival and disease-specific survival in glioma and some other tumors. MiR-105-5p and miR-9-5p were identified as the most potential upstream miRNAs of REST in glioma patient cohort and experiments in vitro. REST expression was positively correlated with infiltration of immune cells and the expression of immune checkpoints such as PD1/PD-L1 and CTLA-4 in glioma. Furthermore, histone deacetylase 1 (HDAC1) was a potential REST-related gene in glioma. Enrichment analysis of REST found chromatin organization and histone modification were the most significant enriched terms, and Hedgehog-Gli pathway might be involved in the effect of REST on the pathogenesis of glioma. Our study suggests REST to be an oncogenic gene and the biomarker of poor prognosis in glioma. High REST expression might affect the tumor microenvironment of glioma. More basic experiments and large clinical trials aimed at the carcinogenetic study of REST in glioma will be needed in the future. [ABSTRACT FROM AUTHOR]

Single-cell multi-omics (scMulti-omics) allows the quantification of multiple modalities simultaneously to capture the intricacy of complex molecular mechanisms and cellular heterogeneity. Existing tools cannot effectively infer the active biological networks in diverse cell types and the response of these networks to external stimuli. Here we present DeepMAPS for biological network inference from scMulti-omics. It models scMulti-omics in a heterogeneous graph and learns relations among cells and genes within both local and global contexts in a robust manner using a multi-head graph transformer. Benchmarking results indicate DeepMAPS performs better than existing tools in cell clustering and biological network construction. It also showcases competitive capability in deriving cell-type-specific biological networks in lung tumor leukocyte CITE-seq data and matched diffuse small lymphocytic lymphoma scRNA-seq and scATAC-seq data. In addition, we deploy a DeepMAPS webserver equipped with multiple functionalities and visualizations to improve the usability and reproducibility of scMulti-omics data analysis. Single-cell multi-omics and deep learning could lead to the inference of biological networks across specific cell types. Here, the authors develop DeepMAPS, a deep learning, graph-based approach for cell-type specific network inference from single-cell multi-omics data that is tested on healthy and tumour tissue datasets. [ABSTRACT FROM AUTHOR]

In summary, the current results demonstrated that withdrawal effects for those with higher levels of internet addiction can be seen in samples whose prime access of the internet is through mobile devices. For the older participants, there was a significant change from zero for those with higher levels of internet addiction and who used social media, I z i = 2.032, I p i = 0.042, but not for the higher internet addiction group not using social media, I z i = 0.319, I p i > 0.30, or for the lower internet groups whether using, I z i = 0.864, I p i > 0.30, or not using, I z i = 0.319, I p i > 0.30, social media. However, with changes in usage patterns of those accessing digital resources (i.e. for social media rather than traditional internet resources), it is unclear whether withdrawal effects would be observed when higher PIU scores are associated with mobile device use for social media. [Extracted from the article]

Many people in this world are fond of reading, and text format is regarded as the official way of communication. This has resulted in an increased production of text data in a highly exponential way. consequently, people were looking for a way where they need not have to spend much time in reading the entire information provided by articles, books and so on. Moreover, people are compelled to read entire newspapers or desired articles in a short span of time in the middle of their busy schedules. So, people were looking for a simplified strategy of "Read less, get more content". Summarization of books,0 articles and newspapers reduces the time taken to understand the content present in them. Abstractive text summarization involves summarizing the given text by reorganizing the whole text using syntactic and semantic text analysis. It includes the capability of synthesizing a compressed form of the original sentences or it may constitute novel sentences with the same semantic sense, which may not be present in the original source document. This system focusses on the different algorithms that have been developed to deal with the challenging problem of Anaphora Resolved Abstractive Text Summarization. It produces an abstractive summary that has mismatches between anaphors and their antecedents. The problem of the mapping of events with their source is addressed by the AR-ATS method, which resolves several types of anaphora that are present in prominent and common text document. Anaphora resolution involves mapping the anaphors with their antecedents which allows the semantic analysis more effective and thereby increases the efficiency of the summary produced by the method. Then the anaphora resolved words are semantically analyzed and create a flawless summary of the text document with complete analysis of the events and their sources. The whole system was successfully evaluated by various benchmark datasets, and it was shown that algorithms mentioned earlier are efficient for abstractive summarization of text. [ABSTRACT FROM AUTHOR]

The inferior colliculus (IC) is critical in initiating acoustically evoked alcohol withdrawal-induced seizures (AWSs). Recently, we reported that systemic inhibition of Ca2+ entry via the reverse mode activity of the Na+/Ca2+ exchanger (NCXrev) suppressed AWSs, suggesting remodeling of NCX expression and function, at least in the IC, the site of AWS initiation. Here, we probe putative changes in protein expression in the IC of NCX isoforms, including NCX type 1 (NCX1), 2 (NCX2), and 3 (NCX3). We also evaluated the efficacy of targeted inhibition of NCX1rev and NCX3rev activity in the IC on the occurrence and severity of AWSs using SN-6 and KB-R943, respectively. We used our well-characterized alcohol intoxication/withdrawal model associated with enhanced AWS susceptibility. IC tissues from the alcohol-treated group were collected 3 h (before the onset of AWS susceptibility), 24 h (when AWS susceptibility is maximal), and 48 h (when AWS susceptibility is resolved) following alcohol withdrawal; in comparison, IC tissues from the control-treated group were collected at 24 h after the last gavage. Analysis shows that NCX1 protein levels were markedly higher 3 and 24 h following alcohol withdrawal. However, NCX3 protein levels were only higher 3 h following alcohol withdrawal. The analysis also reveals that bilateral microinjections of SN-6 (but not KB-R7943) within the IC markedly suppressed the occurrence and severity of AWSs. Together, these findings indicate that NCX1 is a novel molecular target that may play an essential role in the pathogenesis and pathophysiology of AWSs. [ABSTRACT FROM AUTHOR]

Background: Due to complex pathophysiology of functional dyspepsia, medications to treat functional dyspepsia are not effective for all patients. Transcutaneous electrical acustimulation (TEA) is an potentially effective therapy for functional dyspepsia without proofs of definite mechanisms. Aims: We aimed to investigate the therapeutic impacts of TEA on postprandial distress syndrome (PDS) and explore potential neuroimmune mechanisms. Methods: We conducted a double-blinded, randomized, controlled trial in 30 PDS patients randomized for 4-week TEA or sham-TEA. Dyspeptic symptoms, gastric accommodation, gastric emptying and heart rate variability (HRV) were assessed. Duodenal mucosal inflammation was also evaluated. Results: The dyspeptic symptoms were improved with TEA compared with sham-TEA (P = 0.03). The initial satiety volume and the maximum tolerable volume (MTV) were both improved after the TEA treatment, compared with the sham-TEA group (P all < 0.05). The gastric emptying time (T1/2) was not altered with TEA or sham-TEA. The TEA treatment increased vagal activity and decreased sympathovagal ratio assessed by HRV (P all < 0.01). The IL-6 expression in bulb mucosa was downregulated by the TEA treatment compared to the baseline (P < 0.05). Conclusions: Noninvasive TEA improves gastric accommodation and dyspeptic symptoms, possibly by downregulating the IL-6 expression in duodenal bulb mucosa via the vagal efferent pathway. [ABSTRACT FROM AUTHOR]

Adolescence is period characterized by sexual development, increasing romantic relationships, and the initiation of sexual activity. To enhance the exploration of their sexuality, adolescents may look into sexual resources such as pornography. There has been little research in India to understand how much adolescents are exposed to Internet pornography and what are the associated risk factors. This study examined the level of exposure to pornography among adolescents and the associated factors which determine the exposure to pornography in Uttar Pradesh and Bihar. Understanding the Lives of Adolescents and Young Adults (UDAYA) survey data collected in 2015–2016 was used for this study. The study was based on 3885 adolescent boys and 7766 adolescent girls aged 15–19 years. The mean age for adolescent boys was 16.66 years (SD: 1.3), and for girls it was 16.67 years (SD: 1.3). About 47% of adolescent boys but only 6% of girls were exposed to pornography. The likelihood of exposure to pornography was 1.69 times and 2.27 times more likely among adolescents and girls who had their own personal mobile phones, respectively, compared to those who did not have their own personal mobile phones. The odds of exposure to pornography were significantly higher among adolescent boys who had frequent media exposure than those who had no/rare exposure. Programs on life skills and comprehensive sexuality education need to be prioritize. [ABSTRACT FROM AUTHOR]

The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is mainly being used to study demyelination and the mechanisms of remyelination, as well as the efficiency of compounds or therapeutics aiming at remyelination. Although early investigations using high dosages of cuprizone reported the occurrence of hydrocephalus, it has long been assumed that cuprizone feeding at lower dosages does not induce changes at the blood–brain barrier (BBB). Here, by analyzing BBB ultrastructure with high-resolution electron microscopy, we report changes at astrocytic endfeet surrounding vessels in the brain parenchyma. Particularly, edema formation around blood vessels and swollen astrocytic endfeet already occurred after feeding low dosages of cuprizone. These findings indicate changes in BBB function that will have an impact on the milieu of the central nervous system (CNS) in the cuprizone model and need to be considered when studying the mechanisms of de- and remyelination. [ABSTRACT FROM AUTHOR]

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients > 18 years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3 months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation. [ABSTRACT FROM AUTHOR]

Global alignment of complex pseudotime trajectories between different single-cell RNA-seq datasets is challenging, as existing tools mainly focus on linear alignment of single-cell trajectories. Here we present CAPITAL (comparative analysis of pseudotime trajectory inference with tree alignment), a method for comparing single-cell trajectories with tree alignment whereby branching trajectories can be automatically compared. Computational tests on synthetic datasets and authentic bone marrow cells datasets indicate that CAPITAL has achieved accurate and robust alignments of trajectory trees, revealing various gene expression dynamics including gene–gene correlation conservation between different species. Global alignment of complex cell state trajectories between single-cell datasets remains challenging. Here, the authors present a computational method called CAPITAL to compare branching trajectories, and demonstrate that this method achieves accurate and robust alignments. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012–2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36—physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28—CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p < 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both—disease activity and QoL in patients with RA. [ABSTRACT FROM AUTHOR]

Purpose: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases. Methods: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models. Results: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice. Conclusion: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer. [ABSTRACT FROM AUTHOR]

Despite the emergence of experimental methods for simultaneous measurement of multiple omics modalities in single cells, most single-cell datasets include only one modality. A major obstacle in integrating omics data from multiple modalities is that different omics layers typically have distinct feature spaces. Here, we propose a computational framework called GLUE (graph-linked unified embedding), which bridges the gap by modeling regulatory interactions across omics layers explicitly. Systematic benchmarking demonstrated that GLUE is more accurate, robust and scalable than state-of-the-art tools for heterogeneous single-cell multi-omics data. We applied GLUE to various challenging tasks, including triple-omics integration, integrative regulatory inference and multi-omics human cell atlas construction over millions of cells, where GLUE was able to correct previous annotations. GLUE features a modular design that can be flexibly extended and enhanced for new analysis tasks. The full package is available online at https://github.com/gao-lab/GLUE. Different single-cell data modalities are integrated at atlas-scale by modeling regulatory interactions. [ABSTRACT FROM AUTHOR]

The boom in single-cell technologies has brought a surge of high dimensional data that come from different sources and represent cellular systems from different views. With advances in these single-cell technologies, integrating single-cell data across modalities arises as a new computational challenge. Here, we present an adversarial approach, sciCAN, to integrate single-cell chromatin accessibility and gene expression data in an unsupervised manner. We benchmarked sciCAN with 5 existing methods in 5 scATAC-seq/scRNA-seq datasets, and we demonstrated that our method dealt with data integration with consistent performance across datasets and better balance of mutual transferring between modalities than the other 5 existing methods. We further applied sciCAN to 10X Multiome data and confirmed that the integrated representation preserves biological relationships within the hematopoietic hierarchy. Finally, we investigated CRISPR-perturbed single-cell K562 ATAC-seq and RNA-seq data to identify cells with related responses to different perturbations in these different modalities. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies claim that immune checkpoint inhibitors are effective in defective mismatch repair (dMMR) cancers. This raises the question of whether similar therapies are effective in PanNETs (pancreatic neuroendocrine tumors); however, in general, assessment of MMR status in PanNETs has been inconsistent in previous studies. MGMT (O6-methylguanine-DNA methyltransferase) is potentially important for guiding temozolomide (TMZ) therapy in glioblastoma. The number of reports on MGMT expression and promoter methylation in PanNETs are limited. Methods: In this study we assessed the expression of MGMT and MMR proteins MSH2, MSH6, MLH1 and PMS2 in a series of PanNETs by IHC. The methylation status of MGMT and MMR genes in a subset of PanNETs was further assessed by MS-MLPA analysis. Survival curves were constructed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Multivariate Cox proportional hazards regression models were used to determine the prognostic value of the variables. Results: According to evaluation criteria for mismatch repair defects, none of PanNETs shown nuclear staining loss for MSH2, MSH6, MLH1, and PMS2. MGMT low-intensity PanNETs were more commonly found in higher grade, higher Ki67 index and non-functional tumors (P < 0.05). In multivariate analysis, stage III–IV and low-intensity MGMT were shown to be independent risk factors for progression of PanNETs in the entire cohort, non-functioning subgroup and G2 subgroup (P < 0.05 for all). MGMT promoter methylation tended to be higher in the group with low expression of MGMT, However, methylation of MGMT did not statistically correlate with low expression of MGMT (P = 0.153). Conclusions: In conclusion, our study suggests that decreased expression of MGMT but not MMR is associated with a higher risk of progression of pancreatic neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

Cognitive impairments associated with schizophrenia (CIAS) represent a central element of the symptomatology of this severe mental disorder. CIAS substantially determine the disease prognosis and hardly, if at all, respond to treatment with currently available antipsychotics. Remarkably, all drugs presently approved for the treatment of schizophrenia are, to varying degrees, dopamine D2/D3 receptor blockers. In turn, rapidly growing evidence suggests the immense significance of systems other than the dopaminergic system in the genesis of CIAS. Accordingly, current efforts addressing the unmet needs of patients with schizophrenia are primarily based on interventions in other non-dopaminergic systems. In this review article, we provide a brief overview of the available evidence on the importance of specific systems in the development of CIAS. In addition, we describe the promising targets for the development of new drugs that have been used so far. In doing so, we present the most important candidates that have been investigated in the field of the specific systems in recent years and present a summary of the results available at the time of drafting this review (May 2022), as well as the currently ongoing studies. [ABSTRACT FROM AUTHOR]

This study evaluated the effectiveness of a drug and violence resistance educational program (Programa Educacional de Resistência às Drogas e à Violência—PROERD) on latent substance use profiles over a 9-month follow-up period. Two PROERD curricula were evaluated through a cluster randomized controlled trials with two parts that included a total of 4030 fifth-and seventh-grade students in 30 public schools in São Paulo. The intervention groups received 10 PROERD classes delivered by trained police officers, while the control group received no intervention. The primary outcome measures were drug use (any alcohol use, binge drinking, tobacco, marijuana, and inhalants) in the past 6 months, which was assessed using a pretest and a posttest 9 months later. Latent transition analysis was employed to investigate the effect of the intervention on the probabilities associated with the transition across drug use profiles. Latent drug use profiles are underlying subgroups of individuals similar to each other regarding their pattern of polysubstance use. Two different latent drug use profiles were revealed among the fifth graders (abstainers/low users and alcohol users/binge drinkers) and three drug use profiles among the seventh graders (abstainers/low users, alcohol users/binge drinkers, and polydrug users). For both, there was no evidence of the effect of PROERD on drug transition probabilities. In conclusion, the intervention was not successful in changing transitions across adolescent drug use profiles. Thus, the failure of the intervention to affect students' substance use profiles suggests that it should be reconsidered before it is implemented further in Brazilian schools. [ABSTRACT FROM AUTHOR]

Vincristine, an alkaloid extracted from Catharanthus rosea, is a class of chemotherapy drugs that act by altering the function of the microtubules and by inhibiting mitosis. Despite its widespread application, a major adverse effect of vincristine that limits treatment duration is the occurrence of peripheral neuropathy (PN). PN presents with several symptoms including numbness, painful sensation, tingling, and muscle weakness. Vincristine-induced PN involves impaired calcium homeostasis, an increase of reactive oxygen species (ROS), and the upregulation of tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) expression. Several potential approaches to attenuate the vincristine-induced PN including the concomitant administration of chemicals with vincristine have been reported. These chemicals have a variety of pharmaceutical properties including anti-inflammation, antioxidant, and inhibition of calcium channels and calcineurin signaling pathways and increased expression of nerve growth factor (NGF). This review summarized several of these compounds and the mechanisms of action that could lead to effective options in improving vincristine-induced peripheral neuropathy (VIPN). [ABSTRACT FROM AUTHOR]

Diagonal integration of multimodal single-cell data emerges as a trending topic. However, empowering diagonal methods for novel biological discoveries requires bridging huge gaps. Here, we comment on potential risks and future directions of diagonal integration for multimodal single-cell data. [ABSTRACT FROM AUTHOR]

During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis. [ABSTRACT FROM AUTHOR]

Cannabis sativa (C. sativa) is commonly chemically classified based on its Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content ratios. However, the plant contains nearly 150 additional cannabinoids, referred to as minor cannabinoids. Minor cannabinoids are gaining interest for improved plant and product characterization, e.g., for medical use, and bioanalytical questions in the medico-legal field. This study describes the development and validation of an analytical method for the elucidation of minor cannabinoid fingerprints, employing liquid chromatography coupled to high-resolution mass spectrometry. The method was used to characterize inflorescences from 18 different varieties of C. sativa, which were cultivated under the same standardized conditions. Complementing the targeted detection of 15 cannabinoids, untargeted metabolomics employing in silico assisted data analysis was used to detect additional plant ingredients with focus on cannabinoids. Principal component analysis (PCA) was used to evaluate differences between varieties. The overall purpose of this study was to examine the ability of targeted and non-targeted metabolomics using the mentioned techniques to distinguish cannabis varieties from each other by their minor cannabinoid fingerprint. Quantitative determination of targeted cannabinoids already gave valuable information on cannabinoid fingerprints as well as inter- and intra-variety variability of cannabinoid contents. The untargeted workflow led to the detection of 19 additional compounds. PCA of the targeted and untargeted datasets revealed further subgroups extending commonly applied phenotype classification systems of cannabis. This study presents an analytical method for the comprehensive characterization of C. sativa varieties. [ABSTRACT FROM AUTHOR]

Single-cell multi-omics (scMulti-omics) has brought transformative insights into immuno-oncology, demonstrating success in describing novel immune subsets and defining important regulators of antitumor immunity. Here, we give examples of how scMulti-omics has been used in specific tumor studies and discuss how this may develop in the future. [ABSTRACT FROM AUTHOR]

Rationale: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural effects of CBDA are less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine self-administration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis and drug dependence is methamphetamine (METH) sensitisation, where repeated administration of the psychostimulant progressively increases the locomotor effects of METH. Objective: The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of locomotor hyperactivity in rats. Methods: Eighty-six male Sprague Dawley rats underwent METH sensitisation protocol where they were subjected to daily METH (1 mg/kg on days 2 and 8, 5 mg/kg on days 3–7; i.p.) injections for 7 days. After 21 days of withdrawal, rats were given a prior injection of CBD (0, 40 and 80 mg/kg; i.p.) or CBDA (0, 0.1, 10 and 1000 µg/kg; i.p.) and challenged with acute METH (1 mg/kg; i.p.). Locomotor activity was then measured for 60 min. Results: Rats displayed robust METH sensitisation as evidenced by increased locomotor activity to METH challenge in METH-pretreated versus SAL-pretreated rats. CBD (40 and 80 mg/kg) reduced METH-induced sensitisation. There was no effect of any CBDA doses on METH sensitisation or acute METH-induced hyperactivity. Conclusion: These results demonstrate that CBD, but not CBDA, reduces METH sensitisation of locomotor activity in rats at pharmacologically effective doses, thus reinforcing evidence that CBD has anti-addiction and antipsychotic properties. [ABSTRACT FROM AUTHOR]

One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring's brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis. [ABSTRACT FROM AUTHOR]

To evaluate the association between baseline global longitudinal strain (GLS) and ΔGLS (difference of baseline GLS and follow-up) and cardiac resynchronization therapy (CRT) response defined either with clinical or with echocardiographic characteristics. This meta-analysis was performed in accordance to both the Meta-Analysis of Observational Studies in Epidemiology and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Two independent investigators performed a comprehensive systematic search in MedLine, EMBASE and Cochrane databases through September 2019 without limitations. Data analysis was performed by using the Review Manager software (RevMan), version 5.3, and Stata 13 software. A p value of less than 0.05 (two-tailed) was considered statistically significant. Twelve studies (1004 patients, mean age 63.8 years old, males 69.4%) provided data on the association of baseline GLS with the response to CRT therapy. We found that CRT responders had significantly better resting GLS values compared with non-responders [GLS mean difference −2.13 (−3.03, −1.23), p < 0.001, I2 78%]. Furthermore, CRT responders had significantly greater improvement of GLS at follow-up compared with non-responders [ΔGLS mean difference −3.20 (−4.95, −1.45), p < 0.001, I2 66%]. These associations remained significant in a subgroup analysis including only studies with similar CRT response definition. In this meta-analysis, we found that CRT responders had a baseline and ΔGLS significantly higher than the non-responders strengthening the central role of GLS as a tool for selecting candidates for CRT. Furthermore, improved GLS values after CRT may be used to better define CRT responders. [ABSTRACT FROM AUTHOR]

The present study aimed to modulate the oxidative status-mediated polarity of the oocytes for sex-specific sperm fertilization to generate desired sex embryos. In vitro embryos were produced at different oxidative status, varying O2 concentrations, and without/with l-carnitine in maturation and culture media. The majority of the embryos produced at high oxidative stress were males whereas; low oxidative status favoured female embryos production. Low O2 doubled the proportion of female embryos (10.59 vs 21.95%); however, l-carnitine supplementation in media increased approximately seven-folds of the female embryos (12.26 vs. 77.62%) production. Oocytes matured at high oxidative status were in the repolarized state favouring positively charged Y sperm fertilization to produce significantly more male embryos. Low oxidative status favoured negatively charged X sperm fertilization to the oocytes in the depolarized state to produce more female embryos. Intracellular ROS was significantly low in female embryos than in males; however, female embryos were more stressful than males. The study concluded that the oxidative status-mediated alteration in pH of the medium to modulate the intracellular positive ions is the main critical factor to influence the sex of embryos through sex-specific sperms fertilization to the oocytes as per their polarity. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) has poor water solubility and is subjected to extensive first-pass metabolism. These absorption obstacles are responsible for low and variable oral bioavailability of CBD. This study endeavored to improve CBD bioavailability by intramuscular (IM) injection of CBD nanocrystals (CBD-NC). The nanocrystals were prepared by antisolvent precipitation method and were characterized in terms of the particle size, polydispersity index (PDI), zeta potential, morphology, and crystalline status. CBD-NC displayed a particle size of 141.7±1.5 nm, a PDI of 0.18±0.01, and a zeta potential of −25.73 mV. CBD-NC freeze-dried powder using bovine serum albumin (BSA) as cryoprotectant had good redispersibility, and the average particle size was 139.1±1.4 nm after reconstitution. Moreover, these freeze-dried powders were characterized for drug loading and pH and were evaluated for in vitro dissolution and in vivo studies in a rat model. The in vivo results showed that AUC0–24 h and Cmax of CBD by IM injection of CBD nanocrystals increased significantly compared with that of oral (P.O) administration of CBD nanocrystals and CBD oil solution. This underlines the nano-sized CBD could be suggested as a practical and simple nanosystem for IM delivery with improved bioavailability. More importantly, these results pave the way for future development of CBD-NC retentive dosage forms. [ABSTRACT FROM AUTHOR]

The sodium-calcium exchanger (NCX) is essential in maintaining the intracellular calcium balance in neurons and is a regulator of glutamatergic synaptic transmission. NCX dysfunction is implicated in various neurodegenerative and mental illnesses, while pharmacological agents modulating NCX (specific antagonists, allosteric modulators, lithium ions, etc.) are considered potential drugs. However, the effects of the exchanger selective blockers or lithium ions on the electrogenic transport of NCX in neurons have not been previously studied. In this work, using a patch-clamp recording of transmembrane currents in neocortical neurons in primary culture and HEK293 cells, we investigated the effects of the selective NCX antagonists KB-R7943 and SN6 on the current–voltage characterisrics (I–V) of the cell membranes. Also, we examined the influence of lithium ions, a non-transportable NCX substrate, on the NCX transport currents. We show that in cortical neurons, transport current generated by NCX contributes to neuronal I–V, which can be detected when NCX is inhibited by KB-R7943 or SN6. When using a Ca2+-free pipette solution ([Ca2+]i < 100 nM), the exchanger transport current can be recorded only in its reverse mode of operation, when neurons are depolarized, but not in the forward mode of operation at resting potential. Pipette solution with high content of free Ca2+ ([Ca2+]i > 1000 nM) creates the conditions that allow forward operation of the NCX at negative membrane potentials mode of NCX at negative membrane potentials. However, in neurons, unlike HEK293, replacing more than 50% Na+ by Li+ in the extracellular solution inhibits NCX and other sodium-dependent electrogenic transport mechanisms, which is accompanied by a drop in the input resistance and considerably complicates the detection of transport currents generated by NCX. Thus, we demonstrate the possibility of a direct study of NCX transport features and pharmacological characteristics in neurons and HEK293 cells. [ABSTRACT FROM AUTHOR]

Methods for profiling RNA and protein expression in a spatially resolved manner are rapidly evolving, making it possible to comprehensively characterize cells and tissues in health and disease. To maximize the biological insights obtained using these techniques, it is critical to both clearly articulate the key biological questions in spatial analysis of tissues and develop the requisite computational tools to address them. Developers of analytical tools need to decide on the intrinsic molecular features of each cell that need to be considered, and how cell shape and morphological features are incorporated into the analysis. Also, optimal ways to compare different tissue samples at various length scales are still being sought. Grouping these biological problems and related computational algorithms into classes across length scales, thus characterizing common issues that need to be addressed, will facilitate further progress in spatial transcriptomics and proteomics. Regev, Theis and colleagues outline the challenges and concepts of the analysis of spatial transcriptomics data. [ABSTRACT FROM AUTHOR]

Single-cell genomic technologies provide an unprecedented opportunity to define molecular cell types in a data-driven fashion, but present unique data integration challenges. Many analyses require "mosaic integration", including both features shared across datasets and features exclusive to a single experiment. Previous computational integration approaches require that the input matrices share the same number of either genes or cells, and thus can use only shared features. To address this limitation, we derive a nonnegative matrix factorization algorithm for integrating single-cell datasets containing both shared and unshared features. The key advance is incorporating an additional metagene matrix that allows unshared features to inform the factorization. We demonstrate that incorporating unshared features significantly improves integration of single-cell RNA-seq, spatial transcriptomic, SNARE-seq, and cross-species datasets. We have incorporated the UINMF algorithm into the open-source LIGER R package (https://github.com/welch-lab/liger). Single-cell genomic technologies present unique data integration challenges. Here the authors introduce an integrative nonnegative matrix factorization algorithm that incorporates features unshared between datasets when performing dataset integrations, improving integration results for spatial transcriptomic, cross-modality, and cross-species data. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effectiveness of the drug and violence resistance educational program (PROERD) on short-term secondary outcomes, such as intentions to use drugs, attitudes toward drugs, school experience, and life skills (refusal, decision-making, and communication). Two cluster-randomized controlled trials were conducted in 30 public schools in the city of São Paulo (Brazil) with 4030 students (1727 fifth and 2303 seventh graders). The intervention group attended 10 PROERD classes conducted by trained police officers, whereas the control group received no intervention. PROERD is a Brazilian adaptation of the North American Drug Abuse Resistance Education (DARE) program Keepin' it REAL. Data were collected at two time points: pre-intervention and at 9-month follow-up. Two different paradigms were used in the multilevel analysis, complete case (CC), and intention-to-treat (ITT) analyses, using full information maximum likelihood (FIML). We found mixed results. Although the seventh-year curriculum seems to have positive effects on school experience (coef = 0.093; 95% CI: 0.001, −0.185), it also increases the intention to use cigarettes in the future (OR = 1.93, 95% CI: 1.109, 3.379) and the chances of accepting marijuana (OR = 1.62, 95% CI: 1.03, 2.53), and it appears to slightly reduce decision-making skills among fifth graders (coef = −0.078; 95% CI: −0.131, −0.025). Our results suggest that PROERD implementation and cultural adaptation should be reevaluated to understand why the program does not achieve the expected preventive goals and produces potential iatrogenic effects. [ABSTRACT FROM AUTHOR]

Purpose: Adolescents' perceptions of parental norms may influence their substance use. The relationship between parental norms toward cigarette and alcohol use, and the use of illicit substances among their adolescent children is not sufficiently investigated. The purpose of this study was to analyze this relationship, including gender differences, using longitudinal data from a large population-based study. Methods: The present study analyzed longitudinal data from 3171 12- to 14-year-old students in 7 European countries allocated to the control arm of the European Drug Addiction Prevention trial. The impact of parental permissiveness toward cigarettes and alcohol use reported by the students at baseline on illicit drug use at 6-month follow-up was analyzed through multilevel logistic regression models, stratified by gender. Whether adolescents' own use of cigarette and alcohol mediated the association between parental norms and illicit drug use was tested through mediation models. Results: Parental permissive norms toward cigarette smoking and alcohol use at baseline predicted adolescents' illicit drug use at follow-up. The association was stronger among boys than among girls and was mediated by adolescents' own cigarette and alcohol use. Conclusion: Perceived parental permissiveness toward the use of legal drugs predicted adolescents' use of illicit drugs, especially among boys. Parents should be made aware of the importance of norm setting, and supported in conveying clear messages of disapproval of all substances. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19) outbreak turned out the greatest pandemic for decades. It challenged enormously the global health system, forcing it to adjust to the new realities. We aimed to analyze articles covering COVID-19 papers in the rheumatological field and outline emerging topics raising within this frame. We applied the bibliometric database Scopus for our literature search and conducted it on the 5th of June using the following keywords: "rheumatic" OR "rheumatology" OR "rheumatoid arthritis" OR "systemic lupus erythematosus" OR "myositis" OR "systemic sclerosis" OR "vasculitis" OR "arthritis" OR "ankylosing spondylitis" AND "COVID-19". We analyzed all selected articles according to various aspects: type of document, authorship, journal, citations score, rheumatology field, country of origin, language, and keywords. With the help of the software tool VOSviewer version 1.6.15, we have built the visualizing network of authors and keywords co-occurrence. The measurement of the social impact of articles was made using Altmetric data. This study included 1430 retrieved articles with open access mostly. The top five journals in this field were Annals of the Rheumatic Diseases (n = 65), Rheumatology International (n = 51), Clinical Rheumatology (n = 50), Lancet Rheumatology (n = 50), and Frontiers In Immunology (n = 33). Most studies originate from countries with a high incidence of COVID-19 among the general population (the USA—387; Italy—268; UK—184; France—114; Germany—110; India—98 and Spain—96, China—94, Canada—73 Turkey—66). Original Articles (42.1%) were the most common articles' type, following by Letters (24.4%), Reviews (21.7%), Notes (6%), Editorials (4.8%), Erratum (1%). According to the citations scores, articles dedicated to the clinical course of COVID-19 in patients with rheumatic diseases were of the highest importance for the scientific rheumatologic community. Rheumatoid arthritis (n = 527), systemic lupus erythematosus (n = 393), vasculitis (n = 267), myositis (n = 71), systemic sclerosis (n = 68), and psoriatic arthritis (n = 68) were the most widely discussed rheumatic diseases in the view of COVID-19. The analysis of Altmetric and citations scores revealed a moderate correlation between them. This article provides a comprehensive bibliometric and altmetric analysis of COVID-19 related articles in the rheumatology field and summarizes data about features of rheumatology service in the time of the pandemic. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases of the mouse spinal cord have been published in recent years but have not been integrated together. Here, we generate an atlas of spinal cell types based on single-cell transcriptomic data, unifying the available datasets into a common reference framework. We report a hierarchical structure of postnatal cell type relationships, with location providing the highest level of organization, then neurotransmitter status, family, and finally, dozens of refined populations. We validate a combinatorial marker code for each neuronal cell type and map their spatial distributions in the adult spinal cord. We also show complex lineage relationships among postnatal cell types. Additionally, we develop an open-source cell type classifier, SeqSeek, to facilitate the standardization of cell type identification. This work provides an integrated view of spinal cell types, their gene expression signatures, and their molecular organization. Single-cell profiling has led to the identification of diverse cell types. Here, the authors generate a harmonized cell atlas of the mouse post-natal spinal cord. They also provide spatial analysis of the distribution of the identified cell types and an open-source cell type classifier. [ABSTRACT FROM AUTHOR]

Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use indicating cerebellar involvement. This study aimed, for the first time, to investigate the involvement of necroptosis and apoptosis in the VG-induced cerebellar cell loss and the possible protective role of combined omega-3 and vitamin B12 supplementation. Fifty Sprague-Dawley adult male rats (160-200 g) were divided into equal five groups: the control group received normal saline, VG200 and VG400 groups received VG (200 mg or 400 mg/kg, respectively), VG200 + OB and VG400 + OB groups received combined VG (200 mg or 400 mg/kg, respectively), vitamin B12 (1 mg/kg), and omega-3 (1 g/kg). All medications were given daily by gavage for four weeks. Histopathological changes were examined in H&E and luxol fast blue (LFB) stained sections. Immunohistochemical staining for caspase-3 and receptor-interacting serine/threonine-protein kinase-1 (RIPK1) as well as quantitative real-time polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP), caspase-3, and receptor-interacting serine/threonine-protein kinase-3 (RIPK3) genes were performed. VG caused a decrease in the granular layer thickness and Purkinje cell number, vacuolations, demyelination, suppression of MBP gene expression, and induction of caspases-3, RIPK1, and RIPK3 in a dose-related manner. Combined supplementation with B12 and omega-3 improved the cerebellar histology, increased MBP, and decreased apoptotic and necroptotic markers. In conclusion, VG-induced neuronal cell loss is dose-dependent and related to both apoptosis and necroptosis. This could either be ameliorated (in low-dose VG) or reduced (in high-dose VG) by combined supplementation with B12 and omega-3. [ABSTRACT FROM AUTHOR]

Although internet addiction (IA) has been the subject of research in many countries, it is poorly studied in Bangladesh, and previous studies in the country have not examined potential mental health risk factors in relation to the development of IA. The present pilot study attempted to assess the prevalence and associated risk factors of IA among a convenience sample of recently graduated university students actively looking for a job (N = 284) from July to October 2018 in Rajshahi (a city in Bangladesh). The measures included socio-demographic and behavioral variables, the Internet Addiction Test (IAT), and the Depression, Anxiety, and Stress Scale. Surprisingly, no cases of IA were identified in the sample (i.e., the prevalence rate of IA was 0%) which may have been a consequence of the specific population sampled. A total of 3.9% of the participants (n = 11) were classified as excessive users (≥ 60 in IAT). Using regression analysis, the risk factors for excessive internet use were spending more time online (> 5 h daily) and experiencing psychiatric conditions (i.e., depression, stress). It is hoped the present pilot study will facilitate further study in Bangladesh with a more in-depth focus on the socio-demographic and psychiatric morbidities in excessive and problematic internet use. It is also speculated that job-seeking may be a situational protective risk factor for developing IA. [ABSTRACT FROM AUTHOR]

Sexual risk behaviors are closely related to the use of alcohol, tobacco, and other illicit drugs as well as teen dating violence. School-based drug prevention programs that teach social and personal skills could potentially also reduce sexual risk behaviors. We examined the effects of the #Tamojunto program on youth sexual risk behaviors. A randomized controlled trial was conducted with 6391 7th and 8th grade students in 72 public schools in six Brazilian cities. Baseline data were collected prior to program implementation. Two waves of follow-up assessments occurred after 9 and 21 months. Analyses were performed taking into account the multilevel structure of the data. We used intention-to-treat to evaluate changes in the prevalence of sexual risk behaviors over time and between groups. Adolescent age ranged from 11 to 15 years, with a mean of 12.6 ± 0.8 years, and 51.0% were female. Among all participants, receipt of #Tamojunto was associated with higher risk of lifetime sex at 21 months follow-up (OR 1.27, 95% CI [1.03, 1.56]). Among girls, at 9 months follow-up, the program was associated with higher likelihood of having engaged in sex in the last month (OR 1.76, 95% CI [1.13, 2.74]). At 21 months follow-up, girls receiving the program were more likely to report engaging in condomless sex in the last month (OR 1.64, 95% CI [1.07, 2.50]). #Tamojunto may be ineffective and possibly harmful for preventing sexual risk behaviors, especially among girls. We suggest further investigation of the possible mediating role of life skills intervention components on girl's sexual behaviors. [ABSTRACT FROM AUTHOR]

Epilepsy is a debilitating neurological disorder characterised by recurrent seizures for which 30% of patients are refractory to current treatments. The genetic and molecular aetiologies behind epilepsy are under investigation with the goal of developing new epilepsy medications. The transcriptional repressor REST (Repressor Element 1-Silencing Transcription factor) is a focus of interest as it is consistently upregulated in epilepsy patients and following brain insult in animal models of epilepsy and ischemia. This review analyses data from different epilepsy models and discusses the contribution of REST to epileptogenesis. We propose that in healthy brains REST acts in a protective manner to homeostatically downregulate increases in excitability, to protect against seizure through downregulation of BDNF (Brain-Derived Neurotrophic Factor) and its receptor, TrkB (Tropomyosin receptor kinase B). However, in epilepsy patients and post-seizure, REST may increase to a larger degree, which allows downregulation of the glutamate receptor subunit GluR2. This leads to AMPA glutamate receptors lacking GluR2 subunits, which have increased permeability to Ca2+, causing excitotoxicity, cell death and seizure. This concept highlights therapeutic potential of REST modulation through gene therapy in epilepsy patients. [ABSTRACT FROM AUTHOR]

The data driven extrapolation requires the definition of a functional model depending on the available data and has the application scope of providing reliable predictions on the unknown dynamics. Since data might be scattered, we drive our attention towards kernel models that have the advantage of being meshfree. Precisely, the proposed numerical method makes use of the so-called Variably Scaled Kernels (VSKs), which are introduced to implement a feature augmentation-like strategy based on discrete data. Due to the possible uncertainty on the data and since we are interested in modelling the behaviour of the target functions, we seek for a regularized solution by ridge regression. Focusing on polyharmonic splines, we investigate their implementation in the VSK setting and we provide error bounds in Beppo–Levi spaces. The performances of the method are then tested on functions showing exponential or rational decay. Comparisons with Support Vector Regression (SVR) are also carried out and highlight that the proposed approach is effective, particularly since it does not require to train complex architecture constructions. [ABSTRACT FROM AUTHOR]

Two high order multi-augmented and improved augmented finite volume methods are proposed for solving nonlinear degenerate parabolic problems. The solution is represented as Puiseux series expansion in a subdomain with singularity, but contains undetermined parameters called augmented variables. The equation in regular subdomain is treated with high accuracy numerical methods and the unknown parameters can be solved simultaneously from the corresponding nonlinear system. The outstanding advantages of the proposed methods are that the degeneracy can be depicted by the semi-analytic solution, and we can get high order results globally. Specially, the convergence order for nonlinear degenerate parabolic problems is determined by the numerical schemes on regular subdomain, and the augmented methods have good robustness for solving degenerate or singular problems. Numerical examples for some degenerate parabolic equations confirm the efficiency of the new methods including the second and fourth order schemes. In particular, a two-dimensional singular elliptic equation with corner degeneracy is presented in the numerical experiments to demonstrate that the proposed methods can be extended to higher dimensional degenerate problems. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak and lockdown have been associated with multiple consequences for mental health, including an excessive and potentially harmful increase in screen media use. The specific consequences for children, adolescents and young adults with ADHD are still unknown. In the first part of this study, a short review of problematic use of the internet (PUI) in ADHD is presented, showing that patients with ADHD are at risk for different aspects of PUI, such as excessive gaming or problematic social media use. In the second part, we report original data of an online survey on screen media use before, during and after the lockdown completed by parents of children and adolescents clinically referred for ADHD. Parents rated children's/adolescents' media-related behavior and media time on a new screening questionnaire for PUI. Each item was rated three times, referring to the observed behavior before, during and 1–2 months after the lockdown. N = 126 parents of patients referred for ADHD aged 10–18 years participated in the study. Total media time increased by 46% during the lockdown and did not completely return to pre-Corona levels afterwards. Patients with difficulties concentrating, high irritability or deterioration of ADHD problems under lockdown spent more time with screen media than those with milder or no such problems. While the effects of the lockdown on screen media use and its negative impact on everyday life appear to be largely reversible, a small proportion of patients with ADHD apparently continue to show increased media use. [ABSTRACT FROM AUTHOR]

Nigeria has witnessed some significant changes in gambling which have resulted in more people becoming interested in the activity. In an attempt to increase participation, bookmakers have introduced a variety of innovations. Literature has established that this increased participation is inter-generational, cross-cultural, and inter-religious. Particularly among Nigerian youth, participation in gambling cuts across all age groups, socio-economic status, and gender. Both financial and social rewards have been identified as reasons why many youths gamble. Through a qualitative lens, this study investigates how the dynamics of gambling in recent times have affected the biographies of youth within a relatively deprived socio-economic locality in Kwara State, Nigeria. Thirty young gamblers between the ages of 15 and 29 were engaged in a semi-structured interview session. Drawing from the meaning of 'youth' from a sociological lexicon, one can advance this unique narrative of the transitions in gambling activities which can occur as a result of the youths' biographies and socio-economic status. Nigerian youth adopt three specific gambling types as a coping strategy in the face of a crisis-ridden socio-economic structure characterised by poverty, and unemployment. As such, gambling has become a normative activity experimented by the youth to survive the harsh economic conditions. This study therefore argues the need to situate the discourse of youth gambling within the social, cultural, and economic context in which they are located in Nigeria. In addition, the authors provide a framework for understanding the complexity of youth gambling in Nigeria. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700–900 nm for PVP fibers and 1–5 μm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids. [ABSTRACT FROM AUTHOR]