Category: Statistics

Brain Commun. 2021 Aug 6;3(3):fcab146. doi: 10.1093/braincomms/fcab146. eCollection 2021.

ABSTRACT

Identify preoperative imaging findings in hemifacial spasm patients that predict the post-surgical success following microvascular decompression. This is a retrospective study of patients who were diagnosed with hemifacial spasm, had a dedicated cranial nerve MRI, and underwent microvascular decompression for hemifacial spasm. Bilateral facial nerves were interrogated for neurovascular compression. If neurovascular compression was identified, we recorded whether the offending vessel was an artery, a vein or both. The location of the neurovascular compression (proximal nerve versus distal nerve) was noted. The severity of the neurovascular compression was categorized as contact versus deformity of the nerve. Patients were contacted to determine their post-operative spasm status. The relationships between imaging findings and post-surgical outcome were assessed by Chi-square tests, and odds ratios were calculated to quantify the degree of association. The study included 212 patients. Upon follow up, 192 patients were spasm free (90.57%). Imaging findings on the symptomatic side were as follows: arterial neurovascular compression was seen in 207 patients (97.64%), venous only neurovascular compression in two patients (0.94%), and no neurovascular compression in three patients (1.42%). Arterial neurovascular compression along the proximal, susceptible segment of the nerve was observed in 202 patients (95.28%); deformity was observed more commonly than contact alone. Arterial neurovascular compression along the distal segment only of the nerve was observed in five patients (2.36%). In patients with arterial neurovascular compression of the proximal and distal portions of the nerve, 93.07% and 60.0% of patients were spasm-free respectively. If venous neurovascular compression only was observed on imaging, 0% of patients were spasm-free. Patients with arterial neurovascular compression of the susceptible segment are much more likely to be spasm free than patients without this imaging finding, [odds ratio 20.14 (CI 5.08, 79.81), P-value <0.0001]. When comparing the two groups of arterial neurovascular compression (deformity versus contact), no statistically significant difference in outcomes was observed. In patients with hemifacial spasm undergoing microvascular decompression, imaging findings do predict surgical outcome. Patients with arterial neurovascular compression of the proximal, susceptible portion of the nerve are much more likely to be spasm free after surgery than those without this imaging finding. The imaging findings inform the risk benefit analysis and discussion with patients before they undergo microvascular decompression for hemifacial spasm.

PMID:34396106 | PMC:PMC8361424 | DOI:10.1093/braincomms/fcab146

Brain Commun. 2021 Jul 2;3(3):fcab145. doi: 10.1093/braincomms/fcab145. eCollection 2021.

ABSTRACT

Little is known about the characteristics and causes of early-onset cognitive impairment. Responders to the 2001 New York World Trade Center disaster represent an ageing population that was recently shown to have an excess prevalence of cognitive impairment. Neuroimaging and molecular data demonstrate that a subgroup of affected responders may have a unique form of parietal-dominant Alzheimer’s Disease. Recent neuropsychological testing and artificial intelligence approaches have emerged as methods that can be used to identify and monitor subtypes of cognitive impairment. We utilized data from World Trade Center responders participating in a health monitoring program and applied a deep learning approach to evaluate neuropsychological and neuroimaging data to generate a cortical atrophy risk score. We examined risk factors associated with the prevalence and incidence of high risk for brain atrophy in responders who are now at midlife. Training was conducted in a randomly selected two-thirds sample (N = 99) enrolled using of the results of a structural neuroimaging study. Testing accuracy was estimated for each training cycle in the remaining third subsample. After training was completed, the scoring methodology that was generated was applied to longitudinal data from 1441 World Trade Center responders. The artificial neural network provided accurate classifications of these responders in both the testing (Area Under the Receiver Operating Curve, 0.91) and validation samples (Area Under the Receiver Operating Curve, 0.87). At baseline and follow-up, responders identified as having a high risk of atrophy (n = 378) showed poorer cognitive functioning, most notably in domains that included memory, throughput, and variability as compared to their counterparts at low risk for atrophy (n = 1063). Factors associated with atrophy risk included older age [adjusted hazard ratio, 1.045 (95% confidence interval = 1.027-1.065)], increased duration of exposure at the WTC site [adjusted hazard ratio, 2.815 (1.781-4.449)], and a higher prevalence of post-traumatic stress disorder [aHR, 2.072 (1.408-3.050)]. High atrophy risk was associated with an increased risk of all-cause mortality [adjusted risk ratio, 3.19 (1.13-9.00)]. In sum, the high atrophy risk group displayed higher levels of previously identified risk factors and characteristics of cognitive impairment, including advanced age, symptoms of post-traumatic stress disorder, and prolonged duration of exposure to particulate matter. Thus, this study suggests that a high risk of brain atrophy may be accurately monitored using cognitive data.

PMID:34396105 | PMC:PMC8361422 | DOI:10.1093/braincomms/fcab145

Brain Commun. 2021 Jul 2;3(3):fcab139. doi: 10.1093/braincomms/fcab139. eCollection 2021.

ABSTRACT

Metabolomics in the Alzheimer’s Disease Neuroimaging Initiative cohort provides a powerful tool for mapping biochemical changes in Alzheimer’s disease, and a unique opportunity to learn about the association between circulating blood metabolites and brain amyloid-β deposition in Alzheimer’s disease. We examined 140 serum metabolites and their associations with brain amyloid-β deposition, cognition and conversion from mild cognitive impairment to Alzheimer’s disease in the Alzheimer’s Disease Neuroimaging Initiative. Processed [¹⁸F] Florbetapir PET images were used to perform a voxel-wise statistical analysis of the effect of metabolite levels on amyloid-β accumulation across the whole brain. We performed a multivariable regression analysis using age, sex, body mass index, apolipoprotein E ε4 status and study phase as covariates. We identified nine metabolites as significantly associated with amyloid-β deposition after multiple comparison correction. Higher levels of one acylcarnitine (C3; propionylcarnitine) and one biogenic amine (kynurenine) were associated with decreased amyloid-β accumulation and higher memory scores. However, higher levels of seven phosphatidylcholines (lysoPC a C18:2, PC aa C42:0, PC ae C42:3, PC ae C44:3, PC ae C44:4, PC ae C44:5 and PC ae C44:6) were associated with increased brain amyloid-β deposition. In addition, higher levels of PC ae C44:4 were significantly associated with lower memory and executive function scores and conversion from mild cognitive impairment to Alzheimer’s disease dementia. Our findings suggest that dysregulation of peripheral phosphatidylcholine metabolism is associated with earlier pathological changes noted in Alzheimer’s disease as measured by brain amyloid-β deposition as well as later clinical features including changes in memory and executive functioning. Perturbations in phosphatidylcholine metabolism may point to issues with membrane restructuring leading to the accumulation of amyloid-β in the brain. Additional studies are needed to explore whether these metabolites play a causal role in the pathogenesis of Alzheimer’s disease or if they are biomarkers for systemic changes during preclinical phases of the disease.

PMID:34396103 | PMC:PMC8361396 | DOI:10.1093/braincomms/fcab139

Brain Commun. 2021 Jun 26;3(3):fcab143. doi: 10.1093/braincomms/fcab143. eCollection 2021.

ABSTRACT

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain-an index of neuronal damage-were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism-potentially sustained by increased triacylglyceride content-and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.

PMID:34396104 | PMC:PMC8361390 | DOI:10.1093/braincomms/fcab143

NAR Genom Bioinform. 2021 Aug 11;3(3):lqab072. doi: 10.1093/nargab/lqab072. eCollection 2021 Sep.

ABSTRACT

Estimating the co-expression of cell identity factors in single-cell is crucial. Due to the low efficiency of scRNA-seq methodologies, sensitive computational approaches are critical to accurately infer transcription profiles in a cell population. We introduce COTAN, a statistical and computational method, to analyze the co-expression of gene pairs at single cell level, providing the foundation for single-cell gene interactome analysis. The basic idea is studying the zero UMI counts’ distribution instead of focusing on positive counts; this is done with a generalized contingency tables framework. COTAN can assess the correlated or anti-correlated expression of gene pairs, providing a new correlation index with an approximate p-value for the associated test of independence. COTAN can evaluate whether single genes are differentially expressed, scoring them with a newly defined global differentiation index. Similarly to correlation network analysis, it provides ways to plot and cluster genes according to their co-expression pattern with other genes, effectively helping the study of gene interactions, becoming a new tool to identify cell-identity markers. We assayed COTAN on two neural development datasets with very promising results. COTAN is an R package that complements the traditional single cell RNA-seq analysis and it is available at https://github.com/seriph78/COTAN.

PMID:34396096 | PMC:PMC8356963 | DOI:10.1093/nargab/lqab072

Brain Commun. 2021 Jun 4;3(3):fcab128. doi: 10.1093/braincomms/fcab128. eCollection 2021.

ABSTRACT

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder caused by ATP1A3 mutations. Some evidence for disease progression exists, but there are few systematic analyses. Here, we evaluate alternating hemiplegia of childhood progression in humans and in the D801N knock-in alternating hemiplegia of childhood mouse, Mashlool, model. This study performed an ambidirectional (prospective and retrospective data) analysis of an alternating hemiplegia of childhood patient cohort (n = 42, age 10.24 ± 1.48 years) seen at one US centre. To investigate potential disease progression, we used linear mixed effects models incorporating early and subsequent visits, and Wilcoxon Signed Rank test comparing first and last visits. Potential early-life clinical predictors were determined via multivariable regression. We also compared EEG background at first encounter and at last follow-up. We then performed a retrospective confirmation study on a multicentre cohort of alternating hemiplegia of childhood patients from France (n = 52). To investigate disease progression in the Mashlool mouse, we performed behavioural testing on a cohort of Mashlool^– mice at prepubescent and adult ages (n = 11). Results: US patients, over time, demonstrated mild worsening of non-paroxysmal disability index scores, but not of paroxysmal disability index scores. Increasing age was a predictor of worse scores: P < 0.0001 for the non-paroxysmal disability index, intellectual disability scale and gross motor scores. Earliest non-paroxysmal disability index score was a predictor of last visit non-paroxysmal disability index score (P = 0.022), and earliest intellectual disability score was a predictor of last intellectual disability score (P = 0.035). More patients with EEG background slowing were noted at last follow-up as compared to initial (P = 0.015). Similar worsening of disease with age was also noted in the French cohort: age was a significant predictor of non-paroxysmal disability index score (P = 0.001) and first and last non-paroxysmal disability index score scores significantly differed (P = 0.002). In animal studies, adult Mashlool mice had, as compared to younger Mashlool mice, (i) worse balance beam performance; (ii) wider base of support; (iii) higher severity of seizures and resultant mortality; and (iv) no increased predisposition to hemiplegic or dystonic spells. In conclusion, (i) non-paroxysmal alternating hemiplegia of childhood manifestations show, on average over time, progression associated with severity of early-life non-paroxysmal disability and age. (ii) Progression also occurs in Mashlool mice, confirming that ATP1A3 disease can lead to age-related worsening. (iii) Clinical findings provide a basis for counselling patients and for designing therapeutic trials. Animal findings confirm a mouse model for investigation of underlying mechanisms of disease progression, and are also consistent with known mechanisms of ATP1A3-related neurodegeneration.

PMID:34396101 | PMC:PMC8361420 | DOI:10.1093/braincomms/fcab128

Turk J Phys Med Rehabil. 2021 May 25;67(2):233-241. doi: 10.5606/tftrd.2021.6887. eCollection 2021 Jun.

ABSTRACT

OBJECTIVES: This study aims to develop measurement tools for assessing patients’ functional status with rheumatoid arthritis (RA) in terms of upper and lower extremity function and to evaluate the tools’ construct validities with classical and modern psychometric approaches.

PATIENTS AND METHODS: Between April 2010 and April 2012, a total of 300 patients with RA (77 males, 223 females; mean age: 52.3±11.5 years; range, 18 to 82 years) who answered items from a range of widely used instruments were included. After examining initial dimensionality with exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Rasch analysis were used to evaluate the tools’ construct validities. The data-model fit was evaluated with goodness-of-fit (GoF) statistics in CFA, while the tools were examined in terms of item and person fit, unidimensionality and differential item functioning (DIF) from the perspective of Rasch analysis.

RESULTS: According to EFA, two dimensions were identified and named as “self-care-mobility-household activities related to lower extremity” and “self-care-mobility-household activities related to upper extremity” taking into account the factor loadings and the clinical classifications. While the clinical classification was tested with CFA, all items were loaded on their pre-defined dimensions with the factor loadings of ≥0.40 and GoF statistics were within the acceptable ranges. When the “self-care-mobility-household activities related to upper extremity” and “self-care-mobility-household activities related to lower extremity” tools were evaluated via the Rasch analysis, both tools were found to fit the Rasch model expectations, with a mean item fit statistics of -0.528 logit (standard deviation [SD]: 1.365) and -0.213 (SD: 1.168; mean person fit statistics of -0.412 logit (SD: 1.160) and -0.303 logit (SD: 0.859), respectively.

CONCLUSION: For the evaluation of a scale’s construct validity, it is recommended to use the Rasch analysis in tandem with factor analytic methods, as the Rasch analysis explores a scale’s construct validity in terms of item and person fit, DIF and unidimensionality which is the only aspect of the factor analysis.

PMID:34396075 | PMC:PMC8343153 | DOI:10.5606/tftrd.2021.6887

Turk J Phys Med Rehabil. 2021 May 25;67(2):242-249. doi: 10.5606/tftrd.2021.5481. eCollection 2021 Jun.

ABSTRACT

OBJECTIVES: This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP.

PATIENTS AND METHODS: Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms.

RESULTS: There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency).

CONCLUSION: These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

PMID:34396076 | PMC:PMC8343154 | DOI:10.5606/tftrd.2021.5481

J Tradit Chin Med. 2021 Aug;41(4):539-545. doi: 10.19852/j.cnki.jtcm.2021.03.006.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of gecko polysaccharide on the cyclophosphamide-induced suppressed immune response in mice.

METHODS: Polysaccharides were extracted from fresh gecko for the first time using an orthogonal method and protein was removed using Sevag reagent (chloroform:N-butanol, 5:1, v/v). The gecko polysaccharide (GPCE) content was determined by the phenol-concentrated sulfuric acid method. An immunocompromised mouse model was established by intraperitoneally injecting cyclophosphamide at 100 mg/kg into 48 mice. The effects of GPCE on immune regulation in mice were assessed by a thymus-spleen index, serum hemolysin levels, and the proliferation of splenic lymphocytes. Spleen cell CD4+, CD8+, and the CD4+/CD8+ ratio were evaluated by flow cytometry and the tumor necrosis factor-α (TNF-α) levels were measured by ELISA.

RESULTS: The optimal extraction process for gecko polysaccharide included a 1:20 ratio of material to liquid (v/v), an extraction temperature of 60 ℃ and a time of 2 h. The polysaccharide content of the extract was 65.74%. GPCE was analyzed by HPLC and primarily contained glucose and small amounts of mannose, rha, and gal. Compared with the model, the thymus index, the spleen index were indices for GPCE increased with dose, whereas the high and medium groups exhibited significant differences (P < 0.05, P < 0.01). Higher doses of GPCE increased serum TNF-α levels and there was a significant difference between the medium and high GPCE doses and the model (P < 0.05, P < 0.01); The number of CD4+ cells and the CD4+/CD8+ ratio in the gecko polysaccharide group were increased (P < 0.05) and there was no statistical difference in the number of CD8+ cells in the gecko polysaccharide group (P > 0.05); The high GPCE dose significantly increased the level of serum hemolysin (P < 0.01).

CONCLUSIONS: Gecko polysaccharide significantly improved the suppressed immune response induced by cyclophosphamide in mice and promoted the secretion of tumor necrosis factor. The mechanism of gecko polysaccharide as an antitumor agent warrants further study.

PMID:34392646 | DOI:10.19852/j.cnki.jtcm.2021.03.006

Trends Psychiatry Psychother. 2021 Aug 11. doi: 10.47626/2237-6089-2021-0279. Online ahead of print.

ABSTRACT

INTRODUCTION: There are several negative impacts on the physical and mental health of people presenting internet addiction, especially for the development of mood disorders, such as depression.

OBJECTIVE: The aim of the study was to evaluate the association between internet addiction and depressive symptoms, as well as to test the mediating role of physical activity in this association.

METHODS: A cross-sectional study was conducted among undergraduate students from three universities (one private and two public institution) from southern Brazil. Depressive symptoms were measured with the Beck Depression Inventory (BDI-21), internet addiction with the Internet Addiction Test (IAT-20) and physical activity was assessed with the International Physical Activity Questionnaire (IPAQ – short version). Poisson regression and the Karlson-Holm-Breen mediation method were used to the statistical analyses.

RESULTS: We have observed a dose-response relation between internet addiction and depressive symptoms. Levels of physical activity mediated the association between moderate internet addiction and depressive symptoms, accounting for 10.7% of the effect observed.

CONCLUSION: Internet addiction can be detrimental to individuals’ health, and contribute to the development of depressive symptoms. Along with psychological and pharmacological therapies, prescription of physical activities are recommended.

PMID:34392666 | DOI:10.47626/2237-6089-2021-0279