Bone loss and fracture in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: People with multiple sclerosis (PwMS) exhibit reduced bone mineral density (BMD) across several anatomical regions. Studies have indicated that PwMS are at a heightened risk of fractures due to decreased BMD and increased prevalence of osteopenia and osteoporosis. This study aimed to investigate the prevalence and risk of osteopenia, osteoporosis, and fracture among PwMS. METHODS: Relevant studies were identified through comprehensive searches of databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) from January 1, 2000, to January 21, 2024. R software version 4.4.0 and random-effects models were employed to estimate the pooled prevalence, odds ratio (OR), and risk ratio (RR) of osteopenia, osteoporosis, and fracture among PwMS, along with their respective 95 % confidence intervals (CIs). RESULTS: From a total of 2039 articles, 51 studies with 1,503,785 PwMS met our inclusion criteria. The pooled prevalence of osteopenia, osteoporosis, and overall fracture among PwMS was 41.41 % (95 % CI: 36.14% to 46.69 %, I2=97 %), 14.21 % (95 % CI: 10.75 % to 17.68 %, I2=99 %), and 12.84 % (95 % CI: 8.49 % to 17.19 %, I2 = 100 %), respectively. The likelihood of osteopenia (OR=2.02, 95 % CI: 1.46 to 2.8, p-value<0.01, I2=17 %) and osteoporosis (OR=1.71, 95 % CI: 1.27 to 2.31, p-value<0.01, I2=74 %), as well as the probability of overall fracture (RR=1.86, 95 % CI: 1.61 to 2.14, p-value<0.01, I2=74 %) were significantly higher in PwMS than healthy controls (HCs). CONCLUSION: PwMS were at a substantially increased risk of developing osteopenia (2-fold), osteoporosis (1.7-fold), and overall fractures (1.9-fold). Well-designed studies are needed to explore these associations further.

The Role of Glial Fibrillary Acidic Protein as a Biomarker in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta-Analysis.

There is debate on the role of glial fibrillary acidic protein (GFAP) as a reliable biomarker in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), and its potential to reflect disease progression. This review aimed to investigate the role of GFAP in MS and NMOSD. A systematic search of electronic databases, including PubMed, Embase, Scopus, and Web of Sciences, was conducted up to 20 December 2023 to identify studies that measured GFAP levels in people with MS (PwMS) and people with NMOSD (PwNMOSD). R software version 4.3.3. with the random-effect model was used to pool the effect size with its 95% confidence interval (CI). Of 4109 studies, 49 studies met our inclusion criteria encompassing 3491 PwMS, 849 PwNMOSD, and 1046 healthy controls (HCs). The analyses indicated that the cerebrospinal fluid level of GFAP (cGFAP) and serum level of GFAP (sGFAP) were significantly higher in PwMS than HCs (SMD = 0.7, 95% CI: 0.54 to 0.86, p < 0.001, I2 = 29%, and SMD = 0.54, 95% CI: 0.1 to 0.99, p = 0.02, I2 = 90%, respectively). The sGFAP was significantly higher in PwNMOSD than in HCs (SMD = 0.9, 95% CI: 0.73 to 1.07, p < 0.001, I2 = 10%). Among PwMS, the Expanded Disability Status Scale (EDSS) exhibited significant correlations with cGFAP (r = 0.43, 95% CI: 0.26 to 0.59, p < 0.001, I2 = 91%) and sGFAP (r = 0.36, 95% CI: 0.23 to 0.49, p < 0.001, I2 = 78%). Regarding that GFAP is increased in MS and NMOSD and has correlations with disease features, it can be a potential biomarker in MS and NMOSD and indicate the disease progression and disability in these disorders.

Comparing the consequences of COVID-19 vaccination between central nervous system (CNS) demyelinating diseases and other neurological disorders.

BACKGROUND: Vaccination constitutes a crucial preventive measure against COVID-19 infection. Concerns have been raised regarding the efficacy of vaccines in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients due to various immunomodulatory medications and potential adverse events that may impact neurological function. This study aimed to explore the implications of COVID-19 vaccination within MS and NMSOD patients and compare it with other neurological disorders (OND). METHOD: In this cross-sectional study conducted in Isfahan, Iran, baseline data and information on COVID-19 infections and vaccinations were collected from MS, NMOSD, and OND patients between September 2021 and September 2022. The predominant neurological disorders identified among OND patients encompassed headache, epilepsy, and Parkinson's disease. Logistic regression analysis was employed to compare COVID-19 vaccination outcomes among different patient groups, presenting odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The study included 1,307 participants, with 738 having MS, 96 having NMOSD, 76 having clinically isolated syndrome (CIS), and 397 having OND. Significantly higher odds of post-vaccination COVID-19 infection were detected in MS (OR = 3.86, p < 0.001) NMOSD (OR = 2.77, p = 0.015) patients than OND patients. The prior history of COVID-19 infection and the type of vaccine administered did not demonstrate significant associations with the likelihood of post-vaccination COVID-19 infection in MS and NMOSD patients (p > 0.05 for all). There were no significant differences in the rates of adverse events in MS, NMOSD, and OND patients, except the second dose, where NMOSD patients had lower odds than OND patients (OR = 0.55, p = 0.019). CONCLUSION: Although the safety profile of COVID-19 vaccination in MS and NMOSD was similar to that in OND, the rates of post-vaccination COVID-19 infection in MS and NMOSD seem higher than OND. These findings highlight the importance of regular serological monitoring and the potential advantages of supplementary vaccine doses in MS and NMOSD patients.

Cognitive performance and magnetic resonance imaging in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Several studies have shown the different relationships between cognitive functions and structural magnetic resonance imaging (MRI) measurements in people with multiple sclerosis (pwMS). However, there is an ongoing debate regarding the magnitude of correlation between MRI measurements and specific cognitive function tests. This systematic review and meta-analysis aimed to synthesize the most consistent correlations between MRI measurements and cognitive function in pwMS. METHODS: PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were systematically searched up to February 2023, to find relevant data. The search utilized syntax and medical subject headings (MeSH) relevant to cognitive performance tests and MRI measurements in pwMS. The R software version 4.3.3 with random effect models was used to estimate the pooled effect sizes. RESULTS: 13,559 studies were reviewed, of which 136 were included. The meta-analyses showed that thalamic volume had the most significant correlations with Symbol Digit Modalities Test (SDMT) r = 0.47 (95 % CI: 0.39 to 0.56, p < 0.001, I2 = 88 %), Brief Visual Memory Test-Revised-Total Recall (BVMT-TR) r = 0.51 (95 % CI: 0.36 to 0.66, p < 0.001, I2 = 81 %), California Verbal Learning Test-II-Total Recall (CVLT-TR) r = 0.47 (95 % CI: 0.34 to 0.59, p < 0.001, I2 = 69 %,), and Delis-Kaplan Executive Function System (DKEFS) r = 0.48 (95 % CI: 0.34 to 0.63, p < 0.001, I2 = 22 %,). CONCLUSION: We conclude that thalamic volume exhibits highest relationships with information processing speed (IPS), visuospatial learning-memory, verbal learning-memory, and executive function in pwMS. A comprehensive understanding of the intricacies of the mechanisms underpinning this association requires additional research.

Onabotulinum toxin A improves neurogenic detrusor overactivity following spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The current study aimed to assess the efficacy and safety of Onabotulinum toxin A (OBTX-A) treatment for neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients. SETTING: Iran. METHODS: All relevant articles of clinical trials and cohort studies indexed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to September 6, 2022, that addressed OBTX-A treatment for NDO following SCI were included. The quality of eligible studies was evaluated using Cochrane criteria. Also, the weighted mean difference (WMD) was measured with a random-effect model. RESULTS: Regarding the overall efficacy after OBTX-A treatment in the short term, volume per void (VV) (WMD = 118.8, 95% CI: 90.9-146.7, p < 0.01), incontinence-quality of life (IQoL) (WMD = 24.3, 95% CI: 15.8-32.8, p < 0.01), and maximum cystometric capacity (MCC) (WMD = 144.5, 95% CI: 132.3 to 156.7, p < 0.01) significantly increased, while maximum detrusor pressure during storage (MDP) (WMD = -30.5, 95% CI: -35.9 to -25.1, p < 0.01) showed a significant decrease. Furthermore, compared to the placebo group at the 200-unit dose, there was a significant increase in MCC (WMD = 113.5, 95% CI: 84.7 to 142.3, p < 0.01) and a significant decrease in MDP (WMD = -27.2, 95% CI: -39.2 to -15.1, p < 0.01). Urinary tract infection (UTI), hematuria, and autonomic dysreflexia were the most common side effects, occurring at rates of 29.6%, 14.8%, and 13.4%, respectively. CONCLUSION: Our findings highlighted the effectiveness and safety of OBTX-A as a promising treatment of NDO following SCI.

Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.

Background: Maintenance of the genome is essential for cell survival, and impairment of the DNA damage response is associated with multiple pathologies including cancer and neurological abnormalities. DNA-PKcs is a DNA repair protein and a core component of the classical nonhomologous end-joining pathway, but it also has roles in modulating gene expression and thus, the overall cellular response to DNA damage. Methods: Using cells producing either wild-type (WT) or kinase-inactive (KR) DNA-PKcs, we assessed global alterations in gene expression in the absence or presence of DNA damage. We evaluated differential gene expression in untreated cells and observed differences in genes associated with cellular adhesion, cell cycle regulation, and inflammation-related pathways. Following exposure to etoposide, we compared how KR versus WT cells responded transcriptionally to DNA damage. Results: Downregulated genes were mostly involved in protein, sugar, and nucleic acid biosynthesis pathways in both genotypes, but enriched biological pathways were divergent, again with KR cells manifesting a more robust inflammatory response compared to WT cells. To determine what major transcriptional regulators are controlling the differences in gene expression noted, we used pathway analysis and found that many master regulators of histone modifications, proinflammatory pathways, cell cycle regulation, Wnt/ß-catenin signaling, and cellular development and differentiation were impacted by DNA-PKcs status. Finally, we have used qPCR to validate selected genes among the differentially regulated pathways to validate RNA sequence data. Conclusion: Overall, our results indicate that DNA-PKcs, in a kinase-dependent fashion, decreases proinflammatory signaling following genotoxic insult. As multiple DNA-PK kinase inhibitors are in clinical trials as cancer therapeutics utilized in combination with DNA damaging agents, understanding the transcriptional response when DNA-PKcs cannot phosphorylate downstream targets will inform the overall patient response to combined treatment.

Multiple sclerosis and personality traits: associations with depression and anxiety.

BACKGROUND: Depression and anxiety are commonly observed in people with multiple sclerosis (pwMS). There is a growing body of literature supporting the hypothesis that personality traits can influence the mood disorders. This study aimed to investigate the personality traits and their relationships with depression and anxiety among pwMS. METHODS: 234 pwMS were involved in this cross-sectional study. Personality traits, depression, and anxiety were assessed using the NEO Five-Factor Inventory (NEO-FFI) and Hospital Anxiety and Depression Scale (HADS), respectively. Pearson's correlation coefficient and generalized linear model were employed to evaluate the relationships between demographic and clinical characteristics, NEO-FFI, and HADS subscales. RESULTS: In pwMS, longer disease duration was significantly associated with lower level of conscientiousness (ß = - 0.23, p = 0.008) and agreeableness (ß = - 0.2, p = 0.01). Moreover, higher expanded disability status scale (EDSS) of pwMS had a significant relationship with higher level of neuroticism (ß = 0.89, p = 0.01). Increased level of neuroticism was significantly correlated with lower level of extraversion (r = - 0.28, p < 0.001), openness (r = - 0.37, p < 0.001), agreeableness (r = - 0.31, p < 0.001), and conscientiousness (r = - 0.45, p < 0.001). PwMS with higher level of conscientiousness showed more extraversion (r = 0.23, p < 0.001), openness (r = 0.61, p < 0.001), and agreeableness (r = 0.41, p < 0.001). Elevated level of neuroticism was significantly associated with higher level of anxiety (ß = 0.47, p < 0.001) and depression (ß = 0.11, p < 0.001) among pwMS. CONCLUSION: The co-occurrence of depression and anxiety is probably associated with neuroticism among pwMS. Additionally, the impact of personality traits extends to influencing key disease aspects such as physical disability and disease duration in MS.

Risk of dementia following herpes zoster infection among patients undertreatment versus those not: A systematic review and meta-analysis.

Background and Aims: According to the previous studies, herpes zoster (HZ) has been associated with cognitive function and dementia. There is a hypothesis claiming that dementia risk may be reduced by receiving the antiviral treatment for HZ. The purpose of this systematic review and meta-analysis was to shed light on the association between dementia and HZ in individuals receiving and not receiving antiviral medications. Methods: Studies investigating the association between HZ and dementia were identified through a systematic search in PubMed/MEDLINE, Scopus, Embase, Google Scholar, and Cochrane Library databases from January, 2000 to April, 2022. Data on the risk of dementia in HZ-infected patients under and not under antiviral treatment were extracted. The meta-analysis was conducted using a random-effects model. The modified ROBIN-I tool was used to evaluate the risk of bias assessment. By utilizing the funnel plots, publication bias was investigated. Results: Six cohort studies on 538,531 patients were included. The overall risk of bias assessment was moderate. According to evidence-based cohort studies, there was a significant direct association between HZ and risk of dementia in patients with HZ, who did not receive antiviral treatments (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.03 to 1.28, p = 0.01). On the other hand, there was an inverse relationship between HZ and risk of dementia among patients with HZ, who received antiviral treatments (HR: 0.68, 95% CI: 0.59 to 0.77, p < 0.001). Conclusions: This study demonstrated that antiviral therapies may significantly lower the risk of dementia in patients with HZ. This study also confirmed that patients with HZ, without receiving antiviral therapies, may have an increased risk of developing dementia. Further longitudinal research is warranted in this area.

Asthma and chronic obstructive pulmonary disease (COPD) in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Studies have found that multiple sclerosis (MS) has an impact on the initiation or the course of asthma and chronic obstructive pulmonary disease (COPD). This review amied to investigate the prevalence and odds of asthma and COPD among people with MS (pwMS). METHOD: PubMed, Embase, Scopus, and Web of Science were systemically searched from inception to May 2023. R version 4.3.2 and random-effect model were used to calculate the pooled prevalence and odds ratio (OR), with their 95 % confidence interval (CI), in pwMS. RESULTS: A total of 40 studies consisting of 287,702 pwMS were included. 37 studies indicated that the pooled prevalences of asthma and COPD among pwMS were 5.97 % (95 % CI: 4.62 %-7.69 %, I2=99 %) and 3.03 % (95 % CI: 1.82 %-5.00 %, I2=99 %), respectively. 24 studies on 236,469 pwMS and 85,328,673 healthy controls revealed that the overall odds of asthma and COPD in MS were 1.14 (95 % CI: 0.76-1.71, p-value=0.53, I2=97 %) and 1.28 (95 % CI: 1.11-1.47, p-value<0.01, I2=70 %), respectively. CONCLUSION: MS can increased the risk of developing COPD, while asthma does not exhibit a significant relationship with MS. Our study highlights the importance of identifying pwMS who face greater risks of respiratory issues to monitor efficiently and initiate suitable preventative actions.

Insights into the interplay between Epstein-Barr virus (EBV) and multiple sclerosis (MS): A state-of-the-art review and implications for vaccine development.

Background and Aims: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination. Methods: For this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies. Results: Several studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV. Conclusion: Given the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacle.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

BACKGROUND & AIMS: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition. METHODS: RNA sequencing, microarray, NanoString, and immunohistochemistry data of patient HB samples were analyzed for HDAC class expression. Patient-derived spheroids (PDSp) were used to screen combination chemotherapy with an HDAC inhibitor, panobinostat. Patient-derived xenograft (PDX) mouse models were developed and treated with the combination therapy that showed the highest efficacy in the PDSp drug screen. RESULTS: HDAC RNA and protein expression were elevated in HB tumors compared to normal livers. Panobinostat (IC50 of 0.013-0.059 µM) showed strong in vitro effects and was associated with lower cell viability than other HDAC inhibitors. PDSp demonstrated the highest level of cell death with combination treatment of vincristine/irinotecan/panobinostat (VIP). All four models responded to VIP therapy with a decrease in tumor size compared to placebo. After 6 weeks of treatment, two models demonstrated necrotic cell death, with lower Ki67 expression, decreased serum alpha fetoprotein and reduced tumor burden compared to paired VI- and placebo-treated groups. CONCLUSIONS: Utilizing a preclinical HB pipeline, we demonstrate that panobinostat in combination with VI chemotherapy can induce an effective tumor response in models developed from patients with high-risk, relapsed, and treatment-refractory HB. IMPACT AND IMPLICATIONS: Patients with treatment-refractory hepatoblastoma have limited treatment options with survival rates of less than 50%. Our manuscript demonstrates that combination therapy with vincristine, irinotecan, and panobinostat reduces the size of high-risk, relapsed, and treatment-refractory tumors. With this work we provide preclinical evidence to support utilizing this combination therapy as an arm in future clinical trials.

Validity and reliability of the Persian version of Recce stigma scale in people with multiple sclerosis and its impact on quality of life.

BACKGROUND: There is often a fear of social stigma experienced by people with multiple sclerosis (pwMS), which negatively impacts the quality of their lives (QoL). Currently, no Persian-validated questionnaire is available to assess this issue in pwMS. This study aimed to assess the validaty and reliability of the Persian version of Reece Stigma Scale Multiple Sclerosis (RSS-MS) questionnaire for pwMS. METHOD: This cross-sectional was conducted between January and February 2023 in Isfahan, Iran. The demographic and clinical information and the RSS-MS and Multiple Sclerosis Impact Scale-29 (MSIS-29) questionnaires were recorded from pwMS. The content validity index (CVI) and content validity ratio (CVR) have been used to evaluate validity. To identify the factors supporting the MS-related stigma, an exploratory factor analysis (EFA) was conducted. RESULTS: The present study recruited 194 pwMS. Based on factor analysis, only two factors had eigenvalues ≥ 1.0 and exhibited high internal consistency. The Cronbach's α coefficient for internal consistency of the RSS-MS scale was 0.822. More evidence for the construct validity suggested that having higher levels of stigma is significantly correlated with psychological (r = 0.468, p-value < 0.001) and physical dimensions (r = 0.585, p-value < 0.001) of MSIS-29. Expanded Disability Status Scale, disease duration, and treatment duration did not show a significant correlation with stigma (p-value > 0.05). CONCLUSION: This study indicated that the modified version of the RSS-MS scale in the Persian language showed acceptable validity and reliability for evaluating the stigma among Persian pwMS. Furthermore, this study emphasizes the cruciality of monitoring and addressing stigma among pwMS, as it can potentially enhance medical, psychological, physical, and QoL outcomes.

Optical coherence tomography (OCT) measurements and disability in multiple sclerosis (MS): A systematic review and meta-analysis.

BACKGROUND: Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS. METHODS: We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package. RESULTS: From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I2 = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I2 = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I2 = 79%, z-score = -1.79, p = 0.073). CONCLUSION: OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test.

Comparing the hippocampal volumetric atrophy between demented and nondemented individuals with Parkinson's disease: A systematic review and meta-analysis.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative conditions in the world and, when combined with dementia, can lead to immense cerebral volume loss. Of significant importance among all cerebral regions, is the hippocampus. This region plays a pivotal role in memory, and understanding its pathological alterations can answer vital questions regarding dementia. As such, we designed this study to compare the hippocampal volumes of PD patients with dementia (PDD) versus PD without dementia. Methods: PubMed, Web of Science, Scopus, and Embase were searched for relevant studies. We also searched the references sections of all included studies. The original search began in March 2022 and was extended to the end of July 2022. All related data were extracted from the studies. If the studies were conducted on patients from comparable patient groups, the most recent study with the most extensive data set would be included. Results: A statistically significant difference was observed comparing the raw hippocampal volumes in participants with PDD and PD (p value = 0.01). In a comparison of normalized hippocampal volume between PDD and PD, there was a statistically significant difference (p value < 0.01), as well. Conclusion: Although further research is required to illuminate the temporal relation between the onset of dementia and hippocampal atrophy in demented PD individuals, the present study highlights the importance of utilizing volumetric studies on memory-related cerebral regions to diagnose the initiation of dementia in the early stages.

Effective methods for bulk RNA-seq deconvolution using scnRNA-seq transcriptomes.

BACKGROUND: RNA profiling technologies at single-cell resolutions, including single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, scnRNA-seq for short), can help characterize the composition of tissues and reveal cells that influence key functions in both healthy and disease tissues. However, the use of these technologies is operationally challenging because of high costs and stringent sample-collection requirements. Computational deconvolution methods that infer the composition of bulk-profiled samples using scnRNA-seq-characterized cell types can broaden scnRNA-seq applications, but their effectiveness remains controversial. RESULTS: We produced the first systematic evaluation of deconvolution methods on datasets with either known or scnRNA-seq-estimated compositions. Our analyses revealed biases that are common to scnRNA-seq 10X Genomics assays and illustrated the importance of accurate and properly controlled data preprocessing and method selection and optimization. Moreover, our results suggested that concurrent RNA-seq and scnRNA-seq profiles can help improve the accuracy of both scnRNA-seq preprocessing and the deconvolution methods that employ them. Indeed, our proposed method, Single-cell RNA Quantity Informed Deconvolution (SQUID), which combines RNA-seq transformation and dampened weighted least-squares deconvolution approaches, consistently outperformed other methods in predicting the composition of cell mixtures and tissue samples. CONCLUSIONS: We showed that analysis of concurrent RNA-seq and scnRNA-seq profiles with SQUID can produce accurate cell-type abundance estimates and that this accuracy improvement was necessary for identifying outcomes-predictive cancer cell subclones in pediatric acute myeloid leukemia and neuroblastoma datasets. These results suggest that deconvolution accuracy improvements are vital to enabling its applications in the life sciences.

Characteristics of headaches attributed to SARS-CoV-2 vaccination and factors associated with its frequency and prolongation: a cross-sectional cohort study.

Background: Headache is the most frequent neurological adverse event following SARS-CoV-2 vaccines. We investigated the frequency, characteristics, and factors associated with post-vaccination headaches, including their occurrence and prolongation (≥ 48 h). Methods: In this observational cross-sectional cohort study, retrospective data collected between April 2021-March 2022 were analyzed. Univariate and multivariate logistic regressions were used to evaluate the effect of clinicodemographic factors on the odds of post-vaccination headache occurrence and prolongation. Results: Of 2,500 people who were randomly sent the questionnaire, 1822 (mean age: 34.49 ± 11.09, female: 71.5%) were included. Headache prevalence following the first (V1), second (V2), and third (V3) dose was 36.5, 23.3, and 21.7%, respectively (p < 0.001). Post-vaccination headaches were mainly tension-type (46.5%), followed by migraine-like (36.1%). Headaches were mainly bilateral (69.7%), pressing (54.3%), moderate (51.0%), and analgesic-responsive (63.0%). They mainly initiated 10 h [4.0, 24.0] after vaccination and lasted 24 h [4.0, 48.0]. After adjusting for age and sex, primary headaches (V1: aOR: 1.32 [95%CI: 1.08, 1.62], V2: 1.64 [1.15, 2.35]), post-COVID-19 headaches (V2: 2.02 [1.26, 3.31], V3: 2.83 [1.17, 7.47]), headaches following the previous dose (V1 for V2: 30.52 [19.29, 50.15], V1 for V3: 3.78 [1.80, 7.96], V2 for V3: 12.41 [4.73, 35.88]), vector vaccines (V1: 3.88 [3.07, 4.92], V2: 2.44 [1.70, 3.52], V3: 4.34 [1.78, 12.29]), and post-vaccination fever (V1: 4.72 [3.79, 5.90], V2: 6.85 [4.68, 10.10], V3: 9.74 [4.56, 22.10]) increased the odds of post-vaccination headaches. Furthermore, while primary headaches (V1: 0.63 [0.44, 0.90]) and post-COVID-19 headaches (V1: 0.01 [0.00, 0.05]) reduced the odds of prolonged post-vaccination headaches, psychiatric disorders (V1: 2.58 [1.05, 6.45]), headaches lasting ≥48 h following the previous dose (V1 for V2: 3.10 [1.08, 10.31]), and migraine-like headaches at the same dose (V3: 5.39 [1.15, 32.47]) increased this odds. Conclusion: Patients with primary headaches, post-COVID-19 headaches, or headaches following the previous dose, as well as vector-vaccine receivers and those with post-vaccination fever, were at increased risk of post-SARS-CoV-2-vaccination headaches. Primary headaches and post-COVID-19 headaches reduced the odds of prolonged post-vaccination headaches. However, longer-lasting headaches following the previous dose, migraine-like headaches at the same dose, and psychiatric disorders increased this odd.

The Treatment Dilemma of Arteriopathy in Takayasu Arteritis- A State-of-the-Art Approach.

Takayasu Arteritis (TA) is a chronic idiopathic granulomatous pan-arteritis affecting the pulmonary artery, the aorta, and its principal derived branches. The majority of TA patients are female (82.9%-97.0%). Due to the inflammatory character of the illness, arterial stenosis therapy must be treated differently than the atherosclerosis process. In this review paper, we outline a strategy using real-world challenging cases.

A comparison of Barkley's behavioral inhibition model (1997) with Barkley's updated executive functioning model in predicting adult ADHD symptoms: A preliminary report using structural equation modeling.

One of the most comprehensive approaches to explaining attention-deficit/hyperactivity disorder (ADHD) symptoms is Barkley's behavioral inhibition model (BBIM) (1997), in which behavioral inhibition (BI) plays a primary role. Due to the substantial role of working memory (WM) in explaining ADHD symptoms, Barkley recently updated his model and elevated WM from a mediator variable (in BBIM) to a primary position as an exogenous variable alongside BI, and titled his new model as Barkley's updated executive functioning model (BUEFM). However, since the information about the explanatory power of the new model is sparse, this study aims to investigate the impact of this change in WM role by comparing these two models to explain ADHD symptoms. The study involved a sample of 184 (96 females and 88 males) undergraduate students with high ADHD symptoms who were selected using the purposive sampling method. For assessing models, we have utilized four tools that include: CNS-Vital Sign Test Battery; Barkley Deficit in Executive Functioning Scale; self-verbalization questionnaire (SVQ); and trail making test. We analyzed the data by running structural equation modeling (SEM) analysis using IBM AMOS software version 22. The results show that Model Comparison Measurement (e.g. AIC was 197.583 and 144.614 for BBIM and BUEFM, respectively) and Model Fit Indices (e.g. root mean square error of approximation (RMSEA) obtained 0.076 and 0.067 for BBIM and BUEFM, respectively) representing that BUEFM had a better value than BBIM, which means that the BUEFM was considered better fitting to the data. The findings of this study show that BUEFM has more Predictive power than BBIM to predict symptoms of ADHD through the motor control fluency (MOT) variable.

COVID-19 vaccination and alopecia areata: a case report and literature review.

Coronavirus disease 2019 (COVID-19) is a major concern worldwide and various vaccines have been developed and approved for it, however some immune-related issues of COVID-19 vaccines should be considered and individualized for patients. In this study we report two cases of rapidly progressive hair loss following COVID-19 vaccination.