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In this study, we report spray pyrolysis deposition using an alternative precursor solution for the fabrication of MgB2 films. Polycrystalline MgB2 films were prepared by spray pyrolysis, a precursor solution of magnesium diboride nanoparticles, sodium hypophosphite, sodium succinate, sodium acetate and dimethyl sulfoxide on AZ91 magnesium alloys. The spray was carried out using argon as carrier gas at a temperature of 150 °C and a spray rate of 5 ml/min for 60 min. After spraying, the deposited samples were annealed at 300 °C for 15, 30 and 45 min in order to investigate morphological changes and crystallization behaviour. The microstructure, hardness and wettability properties of approximately 30 μm coatings were investigated by X-ray diffraction, scanning electron microscopy, microhardness tester and contact angle meter. Produced coatings showed dense and homogenous structural formation with strong grain connections. As-deposited MgB2 films showed the most pronounced preferred orientation with the (101) reflection and the highest hardness value compared to other annealed coatings at different times. Besides, all the synthesized coatings had a super-hydrophilic surface. [ABSTRACT FROM AUTHOR]

The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition (DPP-4i) on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4i may worsen aggressive traits such as metastasis, Epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while CCappears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

It is a global priority to better manage the biosphere, but action must be informed by comprehensive data on the abundance and distribution of species. The acquisition of such information is currently constrained by high costs. DNA barcoding can speed the registration of unknown animal species, the most diverse kingdom of eukaryotes, as the BIN system automates their recognition. However, inexpensive sequencing protocols are critical as the census of all animal species is likely to require the analysis of a billion or more specimens. Barcoding involves DNA extraction followed by PCR and sequencing with the last step dominating costs until 2017. By enabling the sequencing of highly multiplexed samples, the Sequel platforms from Pacific BioSciences slashed costs by 90%, but these instruments are only deployed in core facilities because of their expense. Sequencers from Oxford Nanopore Technologies provide an escape from high capital and service costs, but their low sequence fidelity has, until recently, constrained adoption. However, the improved performance of its latest flow cells (R10.4.1) erases this barrier. This study demonstrates that a MinION flow cell can characterise an amplicon pool derived from 100,000 specimens while a Flongle flow cell can process one derived from several thousand. At $0.01 per specimen, DNA sequencing is now the least expensive step in the barcode workflow., (© 2024 The Author(s). Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Epstein-Barr virus meningoencephalitis is a rare central nervous system infection that lacks standardized treatment. Immunocompetent and immunosuppressed individuals with this condition frequently have poor prognostic outcomes, making the need to identify therapeutic interventions high. Here, we report 2 pediatric cases of severe Epstein-Barr virus meningoencephalitis, both unresponsive to immunoglobulin and corticosteroid therapy, who demonstrated rapid clinical recovery following rituximab administration. Prognostic outcomes revealed marked improvements in symptoms, neurologic function, and quality of life. Rituximab may offer therapeutic potential in severe and refractory Epstein-Barr virus meningoencephalitis through the medication's target of Epstein-Barr virus harboring B cells. This report emphasizes the need for timely evaluation and consideration of rituximab therapy in immunocompetent pediatric patients with Epstein-Barr virus meningoencephalitis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic disorder among women of reproductive age. Many factors are involved in the development of PCOS, among which genetic predisposition is probably the main contributor that is also influenced by lifestyle and environmental factors. This study aims to determine the prevalence of PCOS in different continents based on Rotterdam, AES and NIH diagnostic criteria., Methods: We conducted a systematic review and meta-analysis to evaluate the prevalence of polycystic ovary syndrome in women according to (Preferred Reporting Items for Systematic Review and Meta-Analysis) PRISMA guidelines. PubMed, Scopus, Science Direct, Web of Science and Google Scholar databases were comprehensively searched until February 2021 for relevant articles. Heterogeneity between the studies was assessed using the I 2 index. Begg and Mazumdar's test was used to evaluate publication bias., Results: A total of 35 studies with 12,365,646 subjects were retrieved. The mean age ranged from 10-45 years. Global prevalence of PCOS was 9.2% (95% CI: 6.8-12.5%) based on meta-analysis, our results showed that the global prevalence of PCOS was 5.5% (95% CI: 3.9-7.7%) based on NIH criteria, 11.5 (95% CI: 6.6-19.4) based on Rotterdam criteria, and 7.1% (95% CI: 2.3-20.2%) based on AES criteria. According to self-report subgroup analysis, the prevalence of PCOS was found to be 11% (95% CI: 5.2-21.8%)., Conclusion: Based on the results of the present study, the prevalence of PCOS in the world was 9.2% (95% CI: 6.8-12.5%). According to the results of the present study and the high prevalence of PCOS, especially in the Africa continent, it is necessary for health systems to implement measures to timely prevent and treat this syndrome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients., Methods: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage., Results: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001)., Conclusions: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes., (© 2024. The Author(s).)

Background: Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning. Given our institution's patient population, we compared the spectrum of knowledge in Hispanic and non-Hispanic patients with pediatric-onset MS (POMS) regarding DMTs and their associated risks during pregnancy and possible disparities in their treatment and counseling., Methods: A small cohort of patients with POMS (n = 22) were surveyed on their knowledge and beliefs surrounding family planning and sexual health counseling. Odds ratios and 95% confidence intervals were used to evaluate the association between survey question responses and ethnicity., Results: No significant differences in beliefs or knowledge regarding sexual health between Hispanic and non-Hispanic participants were identified, but many valuable themes emerged. Internet access and social relationships heavily influence participants' knowledge surrounding birth control and sexual health. Patients also desired continuous engagement in sexual health counseling., Conclusions: In this small pilot cohort, cultural views did not significantly influence whether adolescent and young adult patients with POMS seek sexual health resources. Future studies should aim to identify effective interventions for providers to educate PwMS about sexual health and family planning to address the elevated unplanned pregnancy rate in this population and provide the education these patients have vocalized a desire to receive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD., Methods: This study included individuals with DSRD aged 10-30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants., Results: Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21-97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67-52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89-527.71)., Discussion: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS., (© 2024. The Author(s).)

Objective: To evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS)., Methods: A retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit. Univariate and multivariate analysis using linear and logistic regression models were used to assess associations between patient characteristics and outcomes., Results: In total, 68 patients were reviewed. More than half of patients were female (62 %) and 32 (47 %) were Hispanic/LatinX. Median age at diagnosis was 14.2 years (IQR: 11.0-16.5), and median duration from diagnosis to the latest follow-up was 2.5 years (IQR: 1.6-4.6). Sensory (29.4 %), brainstem (23.5 %), and pyramidal (19.1 %) symptoms were most common. Interferon beta (32.4 %), dimethyl fumarate (27.9 %) and rituximab (26.5 %) were the most frequently used first-line DMT. Patients had a median ARR of 0.5 (IQR: 0.08-0.84), and EDSS score of 1.0 (IQR: 0.0-2.0) at the most recent follow-up. Delayed DMT initiation correlated with higher ARR (R = 0.38, p = 0.0016) and longer 25-ft walk duration (R = 0.34, p = 0.0077). In multivariate analysis, delayed DMT remained a significant predictor of higher ARR (p = 0.002) and longer 25-ft walk duration (p = 0.047). Delayed DMT initiation and use of low/moderate efficacy DMT predicted GAD enhancing lesions at the latest follow-up (p = 0.004 and 0.019 respectively)., Conclusion: Delayed DMT initiation in POMS is linked to unfavorable outcomes, including higher ARR and longer 25-ft walk duration., Competing Interests: Declaration of competing interest Dr. Santoro receives funding through the National Institutes of Health (NHLBI/NICHD). He has previously received funding through the National MS Society and Race to Erase MS Foundation. Dr. Santoro receives consulting fees from UCB for unrelated work on myelin oligodendrocyte glycoprotein related disease. He also receives consulting fees from Cycle Pharmaceuticals on unrelated work to multiple sclerosis and primary periodic paralysis. Other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population., (© 2024. The Author(s).)

Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions., (© 2024 Wiley Periodicals LLC.)

Objective: To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses., Methods: A multicenter, retrospective, case-control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10-30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities., Results: In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18-7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79-3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83-18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78-18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25-0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11-0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02-0.78) compared to individuals without these neuroimaging abnormalities., Interpretation: This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Pediatric onset multiple sclerosis (POMS) commonly occurs at the time of various endocrine changes. Evaluation of the impact of endocrine status on disease severity in POMS has not been previously explored., Objective: This study sought to evaluate if sex and stress hormones in children with POMS impact motor and non-motor diseases severity., Methods: A single-center case control study was performed. Individuals with POMS were compared to individuals without neurologic disease. Each individual had three blood draws assessing stress and sex hormones between 07:00 and 09:00. Measures of fatigue (Epworth sleepiness scale), depression (PHQ-9), and quality of life (PedsQL) assessed at each visit., Results: Forty individuals with POMS and 40 controls were enrolled. Individuals with POMS had lower free testosterone ( p = 0.003), cortisol ( p < 0.001), and ACTH ( p < 0.001) and had higher progesterone ( p = 0.025) levels than controls. Relapses and EDSS were not impacted by endocrine variables. The POMS cohort had a significantly higher Epworth score ( p < 0.001), PHQ-9 score ( p < 0.001), and lower PQL score ( p < 0.001) than controls. Non-motor measures were not associated with endocrine status., Conclusion: Free testosterone, cortisol, ACTH, and progesterone were abnormal in children with POMS although there was no association between endocrine status and markers of disease severity or non-motor symptoms of MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abe, Jafarpour, Vu, O'Brien, Boyd, Vogel, Nguyen, Paulsen, Saucier, Ahsan, Mitchell and Santoro.)

Over the last two decades, neuroimmunologic disorders of childhood have been increasingly described, phenotyped, and treated. These disorders remain rare in the general population and while sharing common therapeutic interventions due to their immune pathophysiology, are heterogeneous with regard to presentation and risk of recurrence. As such, the impact of these disorders on the developing brain has come into the forefront of emerging research in pediatric neuroimmunology. Investigations into the singular impact of monophasic disease on long-term development and the impact of early and aggressive disease-modifying therapy in relapsing conditions are quickly becoming areas of ripe investigation as the field's most optimal way to treat and monitor these conditions over time. Although critically important in evaluating the developing brain, research has been heterogeneous among these diseases and limited by small cohort size. This narrative review details the role of common neuroimmunologic disorders in long-term neurological and cognitive outcomes in children as they develop., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2  = 11.82, P = 0.001), abnormal MRI (χ 2  = 7.78, P = 0.005), and abnormal LP (χ 2  = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD., (© 2023. Springer Nature Limited.)

Background and Purpose: Although many recent studies have analyzed the validation of integrin subunit alpha 4 (ITGA4) biomarker for cancer detection in patients with various malignancies, the diagnostic value of ITGA4 methylation for malignant tumors remains uncertain. We performed a systematic review and meta-analysis to unravel the relationship between ITGA4 promoter methylation status and malignant tumors., Experimental Approach: A meta-analysis was performed using the metaphor package in R 3.5 and Meta-Disc 1.4 software. Data were derived from a search of main electronic databases up to January 2022. SROC analysis was used to evaluate the status of ITGA4 promoter methylation in colorectal cancer (CRC) and other cancers. A total of 1232 tumor samples and 649 non-tumor samples from 13 studies were analyzed., Findings/results: The pooled results including all types of cancer provided evidence that ITGA4 hypermethylation was more frequent in tumor samples than non-tumor samples (OR 13.32, 95% CI 7.96-22.29). Methylation of ITGA4 has a pooled sensitivity of 0.95 (95% CI: 0.94-0.97), a pooled specificity of 0.57 (95% CI: 0.54-0.60), and an area under the curve (AUC) of 0.94. When the analysis was performed independently for CRC, it revealed a higher association (OR = 20.77, 95% CI: 9.15-47.15). The assessment of ITGA4 methylation of tissue samples resulted in a pooled sensitivity of 0.99 (95% CI: 0.97-1.00) and a pooled specificity of 0.90 (95% CI: 0.86-0.93), and AUC of 0.94 for the diagnosis of CRC., Conclusion and Implications: ITGA4 methylation analysis is a reliable method for CRC screening in tissue samples., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2023 Research in Pharmaceutical Sciences.)

Purpose: Hypsarrhythmia is one of the major diagnostic and treatment response criteria in infantile spasms (IS). The clinical and electrophysiological effect of repository corticotropin injection treatment on IS was evaluated using electrophysiological biomarkers., Methods: Consecutive infants (<24 months) treated with repository corticotropin injection for IS were included in this retrospective descriptive study. Inclusion criteria were (1) clinical IS diagnosis, (2) repository corticotropin injection treatment, and (3) consecutive EEG recordings before and after repository corticotropin injection treatment. Patients with tuberous sclerosis complex were excluded. Response to treatment was defined as freedom from IS for at least 7 consecutive days during the treatment and resolution of hypsarrhythmia. The authors defined "relapse" as the recurrence of seizures after an initial response. Electrophysiological biomarker assessment included evaluation of semiautomatic spike counting algorithm, delta power, and delta coherence calculation during non-REM sleep EEG., Results: One hundred fifty patients (83 males; 55%; median age of IS onset: 5.9 months) with complete data were included, including 101 responders (67%, 71 with sustained response, and 30 relapses). Fifty patients (33%) with complete EEG data also underwent advanced EEG analysis. Baseline delta coherence was higher in sustained responders than in nonresponders or patients who relapsed. Greater decreases in semiautomatic spike counting algorithm, delta power, and delta coherence were found in sustained responders compared with nonresponders or patients who relapsed., Conclusions: Repository corticotropin injection treatment was associated with a 67% response rate in patients with IS. Computational biomarkers beyond hypsarrhythmia may provide additional information during IS treatment, such as early determination of treatment response and outcome assessment., Competing Interests: Investigator initiated grant (#IIR-USA-000062) from Mallinckrodt Pharmaceuticals (PI: T.L.). T. Loddenkemper and A. Tanritanir are part of a pending patent application related to EEG biomarkers in the setting of infantile spasms assessment. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Purpose: To compare the number of referrals and conversion rate between the pandemic and pre-pandemic period., Methods: The number of referrals and conversion rate between the 10-month pandemic (March-December 2020) and pre-pandemic (March-December 2019) were evaluated in the two university (mainly non-cosmetic) and private (mainly cosmetic) facial plastic surgery centers. Demographics and monthly number and type (cosmetic and non-cosmetic) of the referrals and surgeries were recorded from the both and cosmetic facial injections (botulinum toxin and filler) and the source of referrals (web- and non-web-based) from the private center. The conversion rate was a ratio of the number of the surgeries to the number of referrals., Results: The number of referrals declined by 7.7% in the private center which was significantly higher for the non-cosmetic (26%) than the cosmetic (0.5%) referrals. It was 32% in the university center. The private center conversion rate significantly (P < 0.001) decreased for both the cosmetic (60%) and non-cosmetic (82%) procedures. It was not significantly different between the cosmetic (65%) and non-cosmetic (58%) procedures in the university center. However, the number of cosmetic facial injections (11%) and the web-based referral source (4%) increased. The recovery was better for the number of referrals (better in the private center) than the conversion rate., Conclusion: The fall in the conversion rate was statistically significant in the private center. While the number of referrals recovered to almost the pre-pandemic level, the conversion rates, despite recovery, remained at a lower level at the end., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Determine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters., Methods: Prospective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures., Results: One-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster., Conclusions: Seizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: There is a gap in the literature regarding genetic underpinnings of pediatric autoimmune CNS diseases. This study explored rare gene variants implicated in immune dysregulation within these disorders., Methods: This was a single-center observational study of children with inflammatory CNS disorder who had genetic testing through next generation focused exome sequencing targeting 155 genes associated with innate or adaptive immunity. For in silico prediction of functional effects of single-nucleotide variants, Polymorphism Phenotyping v2, and Sorting Intolerant from Tolerant were used, and Combined Annotation Dependent Depletion (CADD) scores were calculated. Identified genes were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis., Results: Of 54 patients, 42 (77.8%) carried variant(s), among which 12 (22.2%) had 3-8 variants. Eighty-eight unique single-nucleotide variants of 55 genes were identified. The most variants were detected in UNC13D, LRBA, LYST, NOD2, DOCK8, RNASEH2A, STAT5B, and AIRE. The majority of variants (62, 70.4%) had CADD > 10. KEGG pathway analysis revealed seven genes associated with primary immunodeficiency (Benjamini 1.40E - 06), six genes with NOD-like receptor signaling (Benjamini 4.10E - 04), five genes with Inflammatory Bowel Disease (Benjamini 9.80E - 03), and five genes with NF-kappa B signaling pathway (Benjamini 1.90E - 02)., Discussion: We observed a high rate of identification of rare and low-frequency variants in immune regulatory genes in pediatric neuroinflammatory CNS disorders. We identified 88 unique single-nucleotide variants of 55 genes with pathway analysis revealing an enrichment of NOD2-receptor signaling, consistent with involvement of the pathway within other autoinflammatory conditions and warranting further investigation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Chrysin is a natural bioactive compound that is extracted from many trees, honey, and propolis. Chrysin has several pharmacological activities such as anti-inflammatory, anti-cancer, and antioxidant properties. This study was performed to evaluate the anti-cancer activities of chrysin in cancer therapy. The present study was conducted by systematic review of studies published up to August 2021. Related studies were identified by searching Web of Science (WoS), PubMed, Science Direct, SID, MagIran, Scopus, and Google Scholar databases. The keywords of chrysin, cancer, anti-cancer, and cancer therapy were used for searching. The quality of the studies was assessed by the CONSORT checklist. A total of 21 studies were identified. The results of studies showed that chrysin has an anticancer effect by stimulating apoptosis in a wide range of human cells and rats. Chrysin is also an important factor in inhibiting tumor growth and neoplasticity. Chrysin inhibits the growth and proliferation of cancer cells by inducing cytotoxic effects. Therefore, due to the antitumor effects of chrysin and its safety and non-toxicity towards normal cells, this compound can be considered as an adjuvant along with chemotherapeutic agents in cancer treatment., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022.)

The analysis of dissipatively coupled oscillators is challenging and highly relevant in power grids. Standard mathematical methods are not applicable, due to the lack of network symmetry induced by dissipative couplings. Here we demonstrate a close correspondence between stable synchronous states in dissipatively coupled oscillators, and the winding partition of their state space, a geometric notion induced by the network topology. Leveraging this winding partition, we accompany this article with an algorithms to compute all synchronous solutions of complex networks of dissipatively coupled oscillators. These geometric and computational tools allow us to identify anomalous behaviors of lossy networked systems. Counterintuitively, we show that loop flows and dissipation can increase the system's transfer capacity, and that dissipation can promote multistability. We apply our geometric framework to compute power flows on the IEEE RTS-96 test system, where we identify two high voltage solutions with distinct loop flows., (© 2022. The Author(s).)

Background: Autism spectrum disorder (ASD) is one of the serious developmental disorders that is usually diagnosed below the age of three years. Although the severity of the disease's symptoms varies from patient to patient, the ability to communicate with others is affected in all forms of ASD. This study aimed to determine the prevalence of ASD in high-risk groups by continent., Methods: The present study was conducted by systematic review and meta-analysis from 2008 to July 2021. Databases such as Science Direct, PubMed, Scopus, SID, Magiran, Web of Science (WoS), and Google Scholar from 2008 to July 2021 were searched to find related studies. Data were analysed using Comprehensive Meta-Analysis software (Version 2)., Results: A total of 74 studies with 30,212,757 participants were included in this study. The prevalence of ASD in the world was 0.6% (95% confidence interval: 0.4-1%). Subgroup analyses indicated that the prevalence of ASD in Asia, America, Europe, Africa and Australia was 0.4% (95% CI: 0.1-1), 1% (95% CI: 0.8-1.1), 0.5% (95% CI: 0.2-1), 1% (95% CI: 0.3-3.1), 1.7% (95% CI: 0.5-6.1) respectively., Conclusion: ASD imposes a heavy health burden on communities around the world. Early detection of ASD can reduce the incidence of developmental disorders and improve patients' communication skills. Therefore, health policymakers need to be aware of the prevalence and increasing trend of ASD to implement appropriate planning and interventions to reduce its consequences., (© 2022. The Author(s).)

Purpose: To report the prevalence of unmasked versus masked in subjects seeking for eyelid and eyebrow rejuvenation., Methods: This retrospective study included subjects (>18 years) who were seeking for blepharoplasty and/or eyebrow lift procedures in the year 2020. They were either having No ptosis, Unmasked or Exposed ptosis (complaining of simultaneous droopy eyelid, which was confirmed on examination), or Masked or Hidden ptosis (not complaining of simultaneous droopy eyelid, but its presence was revealed on the examination). Margin reflex distance 1 (MRD1) and levator function (LF) were recorded. Associated ptosis was defined as MRD1 of ≤3 mm and regarded as mild (3 and 2.5 mm), moderate (2 and 1.5 mm), and severe (≤1 mm)., Results: Included were 1401 subjects with a mean age of 47.2 years. The prevalence of masked and unmasked ptosis was 31% (90% unilateral) and 15.6% (59% bilateral), respectively. A significantly younger mean age (45.6 vs. 59.7 years), higher MRD1 (2.6 vs. 1.9 mm), and better LF (13.3 vs. 11.3 mm) were observed in the masked vs. unmasked ptosis group. More than 80% of the subjects with masked ptosis presented with indirect signs. A majority of both groups (68.8% of masked and 63.5% of unmasked ptosis) were mild to moderate., Conclusion: Almost half of the subjects seeking for eyelid and eyebrow rejuvenation had either masked (2/3) or unmasked (1/3) associated ptosis. Masked ptosis was mostly unilateral and presenting with indirect signs of ptosis.

Purpose: The aim of this study was to evaluate and compare early corneal biomechanical changes after small-incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK)., Methods: The study comprised 74 patients eligible for refractive surgery, equally allocated to PRK (37 patients) and SMILE (37 patients). Corneal biomechanical properties were recorded and compared between the 2 groups at preoperatively and 3 months after surgery using a dynamic ultra-high-speed Scheimpflug camera equipped with a noncontact tonometer., Results: Both procedures significantly affected corneal biomechanical properties at 3 months after surgery. Patients in the PRK group showed significantly better results for deformation amplitude ratio (DA ratio) ( P = 0.03), maximum inverse radius (InvRadMax) ( P = 0.02), and A2 time ( P = 0.03). The mean changes in DA ratio, HC radius, InvRadMax, and Ambrosio relational thickness were significantly higher in the SMILE group in comparison with those of the PRK group (all, P < 0.05). In both groups, change in CCT was significantly correlated with changes in DA ratio and InvRadMax ( P < 0.05)., Conclusionss: Both SMILE and PRK refractive surgeries significantly altered corneal biomechanical properties but the changes were more prominent after SMILE., Competing Interests: The authors report no conflicts of interest. We warrant that this paper is original and has not been published in another journal., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Autoimmune encephalitis is a common and treatable cause of encephalitis in children and adults. Individuals present with a variety of symptoms, including altered mental status, behavioral changes, irritability, insomnia, developmental regression, seizures, dyskinetic movements, and autonomic instability. Evaluation includes electroencephalography, magnetic resonance imaging, and lumbar puncture. Once infectious and other causes are reasonably ruled out, treatment should be started empirically without waiting for antibody confirmation. Early clinical suspicion is key, as the outcome depends on early initiation of immunotherapy, including corticosteroids, intravenous immunoglobulin, and/or plasmapheresis. Severe or refractory cases require other treatments, such as rituximab, cyclophosphamide, or other immunotherapies using novel monoclonal antibodies. Psychiatry should be involved early for the management of behavioral issues. Additional considerations include management of seizures and dyskinesias. ICU admission may be required for management of hypoventilation necessitating mechanical ventilation (either intrinsic or iatrogenic, eg, from sedatives), refractory seizures, and dysautonomia. Anti-N-methyl-d-aspartate receptor and other forms of autoimmune encephalitis are less often associated with neoplasia (such as ovarian teratoma) in children compared with adults, but screening and removal of tumor if present should be performed., (© American Academy of Pediatrics, 2022. All rights reserved.)

Purpose: To evaluate the long-term outcomes of the palpebral fissure transfer (PFT) technique without lower eyelid spacer in patients with chronic progressive external ophthalmoplegia (CPEO)., Design: Retrospective interventional case series., Methods: Consecutive patients with CPEO with PFT surgery (2006-2017) and a minimum follow-up of 24 months were included. The PFT included simultaneous levator resection or frontalis sling (based on the levator function and Bell's phenomenon) and lower eyelid retractor recession without spacer. Primary outcome measures included the change in margin reflex distance 1 (MRD-1), MRD-2, and palpebral fissure height (PFH) in the course of time. Potential predictors of keratopathy were also explored., Results: There were 32 patients (64 eyelids) with the mean age and follow-up of 34.1 years (range 15-56 years) and 37.9 months (range 24-72 months), respectively. Mean MRD-1 significantly increased from -0.9 mm to 3.4 mm in postoperative weeks 1 and 2 and 1.8 mm at the last follow-up. Mean MRD-2 significantly decreased from 5.6 mm to 3.7 mm in postoperative weeks 1 and 2 and 5 mm at the last follow-up. Eyes with frank lower eyelid retraction (MRD-2 >5 mm) gained more reduction in MRD-2 compared with those with no sclera show (-0.9 mm vs -0.3 mm, P < .001). Reoperation was performed in 9 eyelids for under- (n = 5) and overcorrection (n = 4). Persistent keratopathy was observed in 3 eyes (4.5%)., Conclusion: Lower eyelid retractor recession without spacer yields significant protective corneal coverage at the critical early postoperative period when the risk of keratopathy is highest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies., Materials and Methods: PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study., Results: Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features., Conclusion: APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.

Background: Major depressive disorder is characterized by a depressed mood or feeling of sadness, loss of interest or pleasure in everyday activities. Depressed individuals have a cognitive impairment, low self-esteem, difficulty making decisions, feeling helpless and hopeless. The factors that have been associated with depression include the lack of social support, living in rural areas, suffering from chronic diseases, smoking, and alcohol abuse. This study aimed to investigate the global prevalence of major depressive disorder in the elderly., Method: The electronic database such as Web of Science (WoS), Scopus, SID, PubMed, Google Scholar, Mag Iran, and IranDoc were systematically searched for studies reporting the prevalence of major depressive disorderin the elderly published up to March 2021. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between the studies was evaluated using the I 2 index. Begg and Mazumdar rank correlation test was used to assess publication bias., Result: A total of 20 studies involving 18953 participants were included in this study. The global prevalence of major depression in the elderly was 13.3 % (95 % CI: 8.4-20.3 %). In the subgroup analysis, the prevalence of major depression in elderly women was 11.9 % (95 % CI: 7.6-18.6) and men 9.7 % (95 % CI: 5.2-17.3). No comparison was made between the two sexes, but based on the confidence intervals and large overlap, the two groups are not statistically different. Among continents, Australia had the highest prevalence of major depression in the elderly at 20.1 % (CI: 14.5-27.2 %). This was followed by Europe at 12.9 % (95 % CI: 5.1-28.9 %)., Conclusion: Major depressive disorder has a growing trend in the elderly population of the world. The prevalence of major depression in the elderly depends on various clinical and demographic factors such as age and gender. Therefore, mental health and the quality of life (QoL) of the elderly are important. The present study emphasizes the importance of social support in mental health that can reduce depression in the elderly., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To compare the conversion rate (number of procedures/referrals) of web-based and non-web-based referrals to a facial plastic surgery practice (2012-2019)., Method: Data on demographics, referral source, patient's concern, and their facial procedures were recorded. Web-based referral sources include website and Instagram. Non-web-based counterparts were the word-of-mouth, medical professionals, and others (TV, radio, printed media). Patient concerns were either cosmetic or noncosmetic (functional). Patients who underwent facial cosmetic surgery and injections (botulinum toxin A, filler, fat) were categorized in the cosmetic procedure group. Patients with functional procedures with or without facial injections were categorized in the noncosmetic procedure group. The conversion rate was defined as the ratio of the number of referrals with different facial procedures to the total number of referrals., Results: Included were 19,965 patients, majority of whom (63.3%) had cosmetic concern. Total, cosmetic, and noncosmetic conversion rates were 30.1%, 27.7%, and 2.4% for the web-based and 24.1%, 19.8%, and 4.3% for the non-web-based referrals, respectively (0.3 < p < 0.4). Cosmetic conversion rate grew from 6.7% in referrals ≤20 to more than 23% in >20 years of age (p = 0.03). It was also significantly (p < 0.001) higher in the referrals with cosmetic (28.3%) than noncosmetic (12.1%) concern. Gender and year of practice did not have a significant effect on the conversion rates., Conclusion: Conversion rates were not significantly different between the web-based and non-web-based referrals. A significantly higher cosmetic conversion rate was observed for the referrals with cosmetic concern and older than 20 years., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA., Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk., Method: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method., Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05)., Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.

Purpose: To analyze the 8-year (2012-2019) change in the patient referral source trends to a plastic surgery practice and the factors affecting them., Methods: Data on demographics, referral source, and patient's concern were recorded. The web-based referral sources were website and Instagram and non-web-based included other patients (word-of-mouth), medical professionals (physician, nurse, and optometrist), and others (printed media, TV, and radio). Patients' concerns were divided into cosmetic and noncosmetic. The first (2012-2015) and second (2016-2019) half of the study period were also compared., Results: Included patients were 19,965. The 8-year referral sources, in order of frequency, were medical professionals (34%), other patients (32.7%), web-based sources (32.5%), and the others (0.7%). The web-based sources significantly increased by 2.4 times in the second half. While they had a third rank after the medical professionals and other patients in the first half of the study period, they became the first in the second half. The non-web-based source showed a decline during the study period. Type of referral sources was not significantly different between the 2 genders. A significantly higher percentage of the patients between 21 and 50 years of age were referred through web-based sources than the other age groups. Patients with cosmetic concerns were 2 times more likely to be referred through web-based sources., Conclusion: The web-based referral sources have significantly grown from the third rank in the beginning to the first one from 2015 till the end of study., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)