@article {pmid37735015,
year = {2023},
author = {Corcia, P and Vourc'h, P and Bernard, E and Cassereau, J and Codron, P and Fleury, MC and Guy, N and Mouzat, K and Pradat, PF and Soriani, MH and Couratier, P},
title = {French National Protocol for genetic of amyotrophic lateral sclerosis.},
journal = {Revue neurologique},
volume = {179},
number = {9},
pages = {1020-1029},
doi = {10.1016/j.neurol.2023.05.005},
pmid = {37735015},
issn = {0035-3787},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Mutation ; },
abstract = {Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics
Mutation

@article {pmid37688479,
year = {2024},
author = {Li, Z and Tian, M and Jia, H and Li, X and Liu, Q and Zhou, X and Li, R and Dong, H and Liu, Y},
title = {Genetic variation in targets of lipid-lowering drugs and amyotrophic lateral sclerosis risk: a Mendelian randomization study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {25},
number = {1-2},
pages = {197-206},
doi = {10.1080/21678421.2023.2255622},
pmid = {37688479},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cholesterol, LDL ; Apolipoproteins B/genetics ; Genetic Variation ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {BACKGROUND: The use of lipid-lowering drugs is still highly controversial in patients with amyotrophic lateral sclerosis (ALS). We performed a drug-target Mendelian randomization (MR) analysis to investigate the effect of targeted lipid-lowering drugs on the risk of ALS.

METHODS: First, we evaluated the causal relationship between HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGCR) inhibitors-taking trait and ALS using a bidirectional two-sample MR study. Second, we investigated the causal relationship between lipid-lowering drugs and ALS through a drug-target MR approach. The summary data for HMGCR inhibitors-taking traits were extracted from a genome-wide association study (GWAS) of medication use and associated disease in the UK Biobank. The summary data for low-density lipoprotein cholesterol and apolipoprotein B (apoB) were extracted from a meta-analysis of GWAS in individuals of European ancestry in the UKB. The GWAS summary data of ALS were obtained from the Project MinE.

RESULTS: Our bidirectional two-sample MR showed that genetically determined increased HMGCR inhibitors-taking trait was an independent risk factor for ALS (odds ratio [OR] = 1.090, 95% confidence interval [CI] = 1.035-1.150, p = 0.001). The results of drug-target MR showed that the increased expression of the HMGCR gene in blood with the higher risk of ALS (OR = 1.21, 95% CI = 1.01-1.46; p = 0.042) through SMR method and the apoB level mediated by the APOB gene increased the risk of ALS (OR = 1.15; 95% CI =1.05-1.25; p = 0.001) through inverse-variance weighted MR method.

CONCLUSION: This present study provides genetic support for a positive causal effect of HMGCR inhibitors-taking trait and ALS. The reason for this may be due to the underlying disease condition behind the medication, rather than the medication itself. Our findings also suggested that HMGCR and apoB inhibitors may have potential protective effects on ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics
Mendelian Randomization Analysis
Genome-Wide Association Study
Cholesterol, LDL
Apolipoproteins B/genetics
Genetic Variation
Polymorphism, Single Nucleotide/genetics

@article {pmid37647907,
year = {2023},
author = {Gondim, FAA and Pinto, WBVR and Chieia, MAT and Correia, CDC and Cunha, FMB and Dourado, MET and França Júnior, MC and Marques Júnior, W and Oliveira, ASB and Rodrigues, CL and Silva, DJD and Dias-Tosta, E},
title = {Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology.},
journal = {Arquivos de neuro-psiquiatria},
volume = {81},
number = {8},
pages = {764-775},
pmid = {37647907},
issn = {1678-4227},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Brazil ; *Laughter ; Crying ; *Motor Neuron Disease ; *Neurology ; },
abstract = {The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/therapy
Brazil
*Laughter
Crying
*Motor Neuron Disease
*Neurology

@article {pmid37516812,
year = {2023},
author = {Yin, Z and Chen, J and Xia, M and Zhang, X and Li, Y and Chen, Z and Bao, Q and Zhong, W and Yao, J and Wu, K and Zhao, L and Liang, F},
title = {Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {12325},
pmid = {37516812},
issn = {2045-2322},
mesh = {Humans ; Cytokines/genetics ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; Fibroblast Growth Factor 2 ; Genome-Wide Association Study ; *Alzheimer Disease ; *Parkinson Disease/genetics ; },
abstract = {Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.},
}

Humans
Cytokines/genetics
*Neurodegenerative Diseases/genetics
Mendelian Randomization Analysis
*Amyotrophic Lateral Sclerosis/genetics
Fibroblast Growth Factor 2
Genome-Wide Association Study
*Alzheimer Disease
*Parkinson Disease/genetics

@article {pmid37211659,
year = {2023},
author = {O'Keefe, DJ},
title = {Commentary on "Do Vaping Prevention Messages Impact Adolescents and Young Adults? A Meta-Analysis of Experimental Studies".},
journal = {Health communication},
volume = {38},
number = {8},
pages = {1723-1726},
doi = {10.1080/10410236.2023.2212467},
pmid = {37211659},
issn = {1532-7027},
mesh = {Humans ; Adolescent ; Young Adult ; *Vaping/prevention & control ; },
abstract = {Preventing vaping by adolescents and young adults is unquestionably an important goal. Ma et al.'s meta-analysis invites the conclusion that vaping prevention messages are effective. This commentary discusses two concerns about that conclusion and the affiliated meta-analysis: (1) None of the analyzed effect sizes describes the effectiveness of vaping prevention messages; the effect sizes describe the difference in effectiveness (the difference on an outcome variable) between the two conditions being compared. (2) As the two conditions being compared vary, so do the relevant conclusions--but the review combines different kinds of comparisons.},
}

Humans
Adolescent
Young Adult
*Vaping/prevention & control

@article {pmid37171577,
year = {2023},
author = {Zhao, B and Jiang, Q and Lin, J and Wei, Q and Li, C and Hou, Y and Cao, B and Zhang, L and Ou, R and Liu, K and Yang, T and Xiao, Y and Huang, R and Shang, H},
title = {Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort.},
journal = {Molecular neurobiology},
volume = {60},
number = {7},
pages = {4150-4160},
pmid = {37171577},
issn = {1559-1182},
support = {2020YJ0457//Sichuan Science and Technology Program/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; 82101485//National Natural Science Foundation of China/ ; 2021-YF05-00242-SN//Science and Technology commission foundation of Chengdu City/ ; },
mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/genetics ; East Asian People ; *Frontotemporal Dementia/genetics ; Genetic Association Studies ; Mutation, Missense/genetics ; Mutation ; Cyclins ; },
abstract = {Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patients, and missense variants were predicted by software analyses. Additionally, we searched PubMed, Embase, and Web of Science for relevant literature and conducted a meta-analysis of the frequency of variants. In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. Among these ALS patients, 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants, and 11 of 15 variants were novel. Seven relevant studies were identified, and a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of males to females in our cohort (10/8) was similar to that in Caucasian populations (4/7) and significantly higher than that in Asian populations (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0 vs. 27.8%); however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohort (1/75) of Caucasian individuals. There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific studies are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants.},
}

Humans
Male
Female
*Amyotrophic Lateral Sclerosis/genetics
East Asian People
*Frontotemporal Dementia/genetics
Genetic Association Studies
Mutation, Missense/genetics
Mutation
Cyclins

@article {pmid36835433,
year = {2023},
author = {Vasilopoulou, C and McDaid-McCloskey, SL and McCluskey, G and Duguez, S and Morris, AP and Duddy, W},
title = {Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36835433},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Genotype ; Motor Neurons ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal late-onset motor neuron disease characterized by the loss of the upper and lower motor neurons. Our understanding of the molecular basis of ALS pathology remains elusive, complicating the development of efficient treatment. Gene-set analyses of genome-wide data have offered insight into the biological processes and pathways of complex diseases and can suggest new hypotheses regarding causal mechanisms. Our aim in this study was to identify and explore biological pathways and other gene sets having genomic association to ALS. Two cohorts of genomic data from the dbGaP repository were combined: (a) the largest available ALS individual-level genotype dataset (N = 12,319), and (b) a similarly sized control cohort (N = 13,210). Following comprehensive quality control pipelines, imputation and meta-analysis, we assembled a large European descent ALS-control cohort of 9244 ALS cases and 12,795 healthy controls represented by genetic variants of 19,242 genes. Multi-marker analysis of genomic annotation (MAGMA) gene-set analysis was applied to an extensive collection of 31,454 gene sets from the molecular signatures database (MSigDB). Statistically significant associations were observed for gene sets related to immune response, apoptosis, lipid metabolism, neuron differentiation, muscle cell function, synaptic plasticity and development. We also report novel interactions between gene sets, suggestive of mechanistic overlaps. A manual meta-categorization and enrichment mapping approach is used to explore the overlap of gene membership between significant gene sets, revealing a number of shared mechanisms.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Genome-Wide Association Study
Genotype
Motor Neurons

@article {pmid36613659,
year = {2022},
author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R},
title = {A Meta-Analysis Study of SOD1-Mutant Mouse Models of ALS to Analyse the Determinants of Disease Onset and Progression.},
journal = {International journal of molecular sciences},
volume = {24},
number = {1},
pages = {},
pmid = {36613659},
issn = {1422-0067},
mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; Superoxide Dismutase-1/genetics/therapeutic use ; Superoxide Dismutase/genetics ; Mice, Transgenic ; Mutation ; Disease Models, Animal ; Disease Progression ; },
abstract = {A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan-Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.},
}

Mice
Animals
*Amyotrophic Lateral Sclerosis/pathology
Superoxide Dismutase-1/genetics/therapeutic use
Superoxide Dismutase/genetics
Mice, Transgenic
Mutation
Disease Models, Animal
Disease Progression

@article {pmid36504126,
year = {2023},
author = {Gautam, AS and Pulivarthi, CB and Singh, RK},
title = {Proinflammatory IL-17 levels in serum/cerebrospinal fluid of patients with neurodegenerative diseases: a meta-analysis study.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {396},
number = {3},
pages = {577-588},
pmid = {36504126},
issn = {1432-1912},
mesh = {Humans ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Interleukin-17 ; Leukocytes, Mononuclear ; *Parkinson Disease ; Cytokines ; *Multiple Sclerosis ; },
abstract = {IL-17 is one of the major proinflammatory cytokine implicated in the pathophysiology of various chronic inflammatory diseases. However, a clear association between the levels of IL-17 and various neurodegenerative diseases is inconclusive due to lack of consistent results reported in several studies. Therefore, we designed and performed a meta-analysis study to assess the levels of IL-17 cytokine in various neurodegenerative diseases. The aim of this meta-analysis study was to assess the level of IL-17 in cerebrospinal fluid/serum of the patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis. An extensive search was performed on electronic databases including PubMed, Cochrane, and Google Scholar to find out the relevant studies for analysis. The quality of selected studies was assessed by Newcastle-Ottawa scale for cohort and case control studies. The standardized mean difference of level of IL-17 in patients with neurodegenerative diseases and control was calculated using RevMan 5 software. A significant increase in the level of serum IL-17 was found to in the patients with neurodegenerative diseases like Alzheimer's disease (p = 0.001) and amyotrophic lateral sclerosis (p = 0.009), whereas IL-17 level in serum of Parkinson's disease (p = 0.22), multiple sclerosis (p = 0.09), and in peripheral blood mononuclear cells of MS patients (p = 0.34) was not found to be significant. IL-17 may be involved in regulation of neuronal inflammation during the pathogenesis of these neurodegenerative disease, and its specific inhibition could be a potential therapeutic target.},
}

Humans
*Neurodegenerative Diseases
*Alzheimer Disease
*Amyotrophic Lateral Sclerosis
Interleukin-17
Leukocytes, Mononuclear
*Parkinson Disease
Cytokines
*Multiple Sclerosis

@article {pmid36460467,
year = {2023},
author = {Janse van Mantgem, MR and van Rheenen, W and Hackeng, AV and van Es, MA and Veldink, JH and van den Berg, LH and van Eijk, RPA},
title = {Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis: A Meta-analysis and Population-Based Study.},
journal = {Neurology},
volume = {100},
number = {10},
pages = {e1062-e1071},
pmid = {36460467},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Genome-Wide Association Study ; Triglycerides ; Cholesterol, HDL ; Biomarkers ; },
abstract = {BACKGROUND AND OBJECTIVE: To explore the association between lipids, polygenic profile scores (PPS) for biomarkers of lipid metabolism, markers of disease severity, and survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We meta-analyzed the current literature on the prognostic value of lipids in patients with ALS. Subsequently, we evaluated the relationship between lipid levels at diagnosis, clinical disease stage, and survival in all consecutive patients diagnosed in the Netherlands. We determined the hazard ratio (HR) of each lipid for overall survival, defined as death from any cause. A subset of patients was matched to a previous genome-wide association study; data were used to calculate PPS for biomarkers of lipid metabolism and to determine the association between observed lipid levels at diagnosis and survival.

RESULTS: Meta-analysis of 4 studies indicated that none of the biomarkers of the lipid metabolism were statistically significantly associated with overall survival; there was, however, considerable heterogeneity between study results. Using individual patient data (N = 1,324), we found that increased high-density lipoprotein (HDL) cholesterol was associated with poorer survival (HR of 1.33 (95% CI 1.14-1.55, p < 0.001)). The correlation between BMI and HDL cholesterol (Pearson r -0.26, 95% CI -0.32 to -0.20) was negative and between BMI and triglycerides (TG) positive (Pearson r 0.18, 95% CI 0.12-0.24). Serum concentrations of total cholesterol and LDL cholesterol were lower in more advanced clinical stages (both p < 0.001). PPS for biomarkers of lipid metabolism explained 1.2%-13.1% of their variance at diagnosis. None of the PPS was significantly associated with survival (all p > 0.50).

DISCUSSION: Lipids may contain valuable information about disease severity and prognosis, but their main value may be driven as a consequence of disease progression. Our results underscore that gaining further insight into lipid metabolism and longitudinal data on serum concentrations of the lipid profile could improve the monitoring of patients and potentially further disentangle ALS pathogenesis.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism
Genome-Wide Association Study
Triglycerides
Cholesterol, HDL
Biomarkers

@article {pmid36252825,
year = {2022},
author = {Román-Caballero, R and Lupiáñez, J},
title = {Suggestive but not conclusive: An independent meta-analysis on the auditory benefits of learning to play a musical instrument. Commentary on.},
journal = {Neuroscience and biobehavioral reviews},
volume = {142},
number = {},
pages = {104916},
doi = {10.1016/j.neubiorev.2022.104916},
pmid = {36252825},
issn = {1873-7528},
mesh = {Humans ; *Music ; Auditory Perception ; Learning ; },
abstract = {The literature on musical training suggests benefits of this activity on auditory skills (i.e., near transfer) and general cognitive abilities (i.e., far transfer). However, other positions have taken those results more skeptically, rather arguing that studies with positive outcomes suffer from methodological issues that impede inferences of causality. In the context of this debate, we conducted an independent meta-analysis similar to one recently published by Neves et al.'s, also showing auditory benefits of musical training. Our meta-analysis suggests that the available evidence is not sufficient to reach firm conclusions as interventions with design-quality features (randomization and active control) are still scarce. Moreover, the reviewed studies measured auditory skills with tests based on same/different judgments that rely on short-term memory, therefore being less sensitive to changes produced by musicmaking experiences. Although the evidence is not conclusive, the results are in line with those observed with other cognitively stimulating activities and suggest a positive impact of musical training on auditory skills. Thus, the available evidence does not support extreme versions of skepticism.},
}

Humans
*Music
Auditory Perception
Learning

@article {pmid36116424,
year = {2022},
author = {Lu, WZ and Lin, HA and Hou, SK and Lee, CF and Bai, CH and Lin, SF},
title = {Split-hand index for amyotrophic lateral sclerosis diagnosis: A frequentist and Bayesian meta-analysis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {143},
number = {},
pages = {56-66},
doi = {10.1016/j.clinph.2022.08.020},
pmid = {36116424},
issn = {1872-8952},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Bayes Theorem ; Hand ; Humans ; Muscle, Skeletal ; ROC Curve ; },
abstract = {OBJECTIVE: Preferential wasting of the thenar muscles, the split-hand sign, may be used for early diagnosis of amyotrophic lateral sclerosis (ALS).

METHODS: Electronic databases were searched for studies assessing the split-hand index (SHI) and the compound muscle action potential (CMAP) amplitudes of abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM). The SHI was obtained by multiplying CMAP amplitudes of APB and FDI and dividing the product by the CMAP amplitude of ADM. The Bayesian analysis was used for validation.

RESULTS: In total, 17 studies and 1635 patients were included. Our meta-analysis revealed that ALS patients had significantly decreased SHI (standardized mean difference [SMD], -1.60, P < 0.001), CMAP of the APB (SMD, -1.67, P < 0.001), FDI (SMD, -1.12, P < 0.001), and ADM (SMD, -1.09, P < 0.001). The binormal receiver operating characteristic curve analysis showed a threshold of < 7.4 for SHI, and cutoff values of < 6.4 mV for APB and < 8.4 mV for FDI, respectively. The Bayesian analysis validated decreased SHI in ALS patients (posterior mean difference of - 5.91).

CONCLUSIONS: An SHI of < 7.4 can be used facilitating earlier diagnosis of ALS.

SIGNIFICANCE: SHI can be used as a standard neurophysiological biomarker for early diagnosis.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Bayes Theorem
Hand
Humans
Muscle, Skeletal
ROC Curve

@article {pmid35946434,
year = {2022},
author = {Cao, MC and Scotter, EL},
title = {Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.},
journal = {Disease models & mechanisms},
volume = {15},
number = {9},
pages = {},
pmid = {35946434},
issn = {1754-8411},
mesh = {*Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Humans ; RNA ; },
abstract = {TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function. Here, we conducted re-analysis and meta-analysis of publicly available RNA-sequencing datasets from six TDP-43-knockdown models, and TDP-43-immunonegative neuronal nuclei from ALS/FTD brain, to identify differentially expressed genes (DEGs) and differential exon usage (DEU) events. There was little overlap in DEGs between knockdown models, but PFKP, STMN2, CFP, KIAA1324 and TRHDE were common targets and were also differentially expressed in TDP-43-immunonegative neurons. DEG enrichment analysis revealed diverse biological pathways including immune and synaptic functions. Common DEU events in human datasets included well-known targets POLDIP3 and STMN2, and novel targets EXD3, MMAB, DLG5 and GOSR2. Our interactive database (https://www.scotterlab.auckland.ac.nz/research-themes/tdp43-lof-db/) allows further exploration of TDP-43 DEG and DEU targets. Together, these data identify TDP-43 targets that can be exploited therapeutically or used to validate loss-of-function processes. This article has an associated First Person interview with the first author of the paper.},
}

*Amyotrophic Lateral Sclerosis/pathology
DNA-Binding Proteins/genetics/metabolism
*Frontotemporal Dementia/genetics/pathology
Humans
RNA

@article {pmid35820692,
year = {2022},
author = {de Jong, VMT and Rousset, RZ and Antonio-Villa, NE and Buenen, AG and Van Calster, B and Bello-Chavolla, OY and Brunskill, NJ and Curcin, V and Damen, JAA and Fermín-Martínez, CA and Fernández-Chirino, L and Ferrari, D and Free, RC and Gupta, RK and Haldar, P and Hedberg, P and Korang, SK and Kurstjens, S and Kusters, R and Major, RW and Maxwell, L and Nair, R and Naucler, P and Nguyen, TL and Noursadeghi, M and Rosa, R and Soares, F and Takada, T and van Royen, FS and van Smeden, M and Wynants, L and Modrák, M and , and Asselbergs, FW and Linschoten, M and , and Moons, KGM and Debray, TPA},
title = {Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.},
journal = {BMJ (Clinical research ed.)},
volume = {378},
number = {},
pages = {e069881},
pmid = {35820692},
issn = {1756-1833},
mesh = {*COVID-19 ; Data Analysis ; Hospital Mortality ; Humans ; *Models, Statistical ; Prognosis ; },
abstract = {OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.

DESIGN: Two stage individual participant data meta-analysis.

SETTING: Secondary and tertiary care.

PARTICIPANTS: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.

DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge.

Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.

METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.

MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality.

RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).

CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.},
}

*COVID-19
Data Analysis
Hospital Mortality
Humans
*Models, Statistical
Prognosis

@article {pmid35789175,
year = {2022},
author = {Walsh, CJ and Batt, J and Herridge, MS and Mathur, S and Bader, GD and Hu, P and Khatri, P and Dos Santos, CC},
title = {Comprehensive multi-cohort transcriptional meta-analysis of muscle diseases identifies a signature of disease severity.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {11260},
pmid = {35789175},
issn = {2045-2322},
support = {MOP-137002//CIHR/Canada ; MOP-106545//CIHR/Canada ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Cohort Studies ; Humans ; *Muscular Diseases/genetics ; Quadriceps Muscle ; Severity of Illness Index ; },
abstract = {Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a "leave-one-disease-out" analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = -0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = -0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10[-3]) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10[-9]). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.},
}

*Amyotrophic Lateral Sclerosis/genetics
Cohort Studies
Humans
*Muscular Diseases/genetics
Quadriceps Muscle
Severity of Illness Index

@article {pmid35703478,
year = {2022},
author = {Li, Z and Zheng, Y and Li, D and Wang, X and Cheng, S and Luo, X and Wen, A},
title = {Low-Dose NOACs Versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Asian Patients with NVAF: A Meta-Analysis.},
journal = {Anatolian journal of cardiology},
volume = {26},
number = {6},
pages = {424-433},
pmid = {35703478},
issn = {2149-2271},
mesh = {Administration, Oral ; Anticoagulants/therapeutic use ; *Atrial Fibrillation/complications ; Gastrointestinal Hemorrhage/complications/drug therapy ; Humans ; Intracranial Hemorrhages/complications/drug therapy ; *Stroke/complications/prevention & control ; Treatment Outcome ; Warfarin/therapeutic use ; },
abstract = {BACKGROUND: The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled tri- als and cohort studies.

METHODS: Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were sys- tematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.

RESULTS: Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed compa- rable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemor- rhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).

CONCLUSION: Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagu- lants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastroin- testinal hemorrhage. Further, high qualified studies are warranted.},
}

Administration, Oral
Anticoagulants/therapeutic use
*Atrial Fibrillation/complications
Gastrointestinal Hemorrhage/complications/drug therapy
Humans
Intracranial Hemorrhages/complications/drug therapy
*Stroke/complications/prevention & control
Treatment Outcome
Warfarin/therapeutic use

@article {pmid35363117,
year = {2023},
author = {Medrano, NW and Villarreal, CL and Mann, NC and Price, MA and Nolte, KB and MacKenzie, EJ and Bixby, P and Eastridge, BJ and , },
title = {Activation and On-Scene Intervals for Severe Trauma EMS Interventions: An Analysis of the NEMSIS Database.},
journal = {Prehospital emergency care},
volume = {27},
number = {1},
pages = {46-53},
doi = {10.1080/10903127.2022.2053615},
pmid = {35363117},
issn = {1545-0066},
mesh = {Humans ; Databases, Factual ; *Emergency Medical Services ; Information Systems ; Retrospective Studies ; Time Factors ; },
abstract = {Objective: Time to care is a determinant of trauma patient outcomes, and timely delivery of trauma care to severely injured patients is critical in reducing mortality. Numerous studies have analyzed access to care using prehospital intervals from a Carr et al. meta-analysis of studies from 1975 to 2005. Carr et al.'s research sought to determine national mean activation and on-scene intervals for trauma patients using contemporary emergency medical services (EMS) records. Since the Carr et al. meta-analysis was published, the National Highway Traffic Safety Administration (NHTSA) created and refined the National Emergency Medical Services Information System (NEMSIS) database. We sought to perform a modern analysis of prehospital intervals to establish current standards and temporal patterns.Methods: We utilized NEMSIS to analyze EMS data of trauma patients from 2016 to 2019. The dataset comprises more than 94 million EMS records, which we filtered to select for severe trauma and stratified by type of transport and rurality to calculate mean activation and on-scene intervals. Furthermore, we explored the impact of basic life support (BLS) and advanced life support (ALS) of ground units on activation and on-scene time intervals.Results: Mean activation and on-scene intervals for ground transport were statistically different when stratified by rurality. Urban, suburban, and rural ground activation intervals were 2.60 ± 3.94, 2.88 ± 3.89, and 3.33 ± 4.58 minutes, respectively. On-scene intervals were 15.50 ± 10.46, 17.56 ± 11.27, and 18.07 ± 16.13 minutes, respectively. Mean helicopter transport activation time was 13.75 ± 7.44 minutes and on-scene time was 19.42 ± 16.09 minutes. This analysis provides an empirically defined mean for activation and on-scene times for trauma patients based on transport type and rurality. Results from this analysis proved to be significantly longer than the previous analysis, except for helicopter transport on-scene time. Shorter mean intervals were seen in ALS compared to BLS for activation intervals, however ALS on-scene intervals were marginally longer than BLS.Conclusions: With the increasing sophistication of geospatial technologies employed to analyze access to care, these intervals are the most accurate and up-to-date and should be included in access to care models.},
}

Humans
Databases, Factual
*Emergency Medical Services
Information Systems
Retrospective Studies
Time Factors

@article {pmid35264038,
year = {2022},
author = {Erazo, D and Luna, J and Preux, PM and Medina, MT and Magne, J and Boumediene, F and Couratier, P},
title = {Amyotrophic lateral sclerosis mortality rates in Latin America and the Caribbean: a meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {7-8},
pages = {608-619},
doi = {10.1080/21678421.2022.2048310},
pmid = {35264038},
issn = {2167-9223},
mesh = {Humans ; Latin America/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Ethnicity ; Caribbean Region ; Europe ; },
abstract = {Background: Recent studies have described a low occurrence of Amyotrophic Lateral Sclerosis (ALS) in Latin America. Significant differences in ALS risk have been reported among ethnic populations in the region. We conducted a meta-analysis using population-based data to describe ALS mortality rates in Latin America. We explored sources of heterogeneity among key covariates.Methods: National mortality registries from Latin American countries were searched to identify ALS deaths according to the International Classification of Diseases (ICD-9: code 335.2 and ICD-10: code G12.2). Crude and standardized mortality rates were calculated. A random-effect meta-analysis was conducted to estimate pooled mortality rates. Subgroup analysis was performed as a means of investigating heterogeneity.Results: Overall, 28,548 ALS deaths and 819 million person-years of follow-up (PYFU) from ten Latin American countries were considered. Standardized mortality varied among countries. The highest mortality rates were observed in Uruguay and Costa Rica at 1.3 and 1.2 per 100,000 PYFU, respectively. The pooled crude mortality rate was 0.38 (95%CI: 0.28-0.53) and the pooled standardized mortality was 0.62 (95%CI: 0.49-0.77) per 100,000 PYFU. Heterogeneity was high (I2: 99.9%, Cochran's Q p < 0.001). Subgroup analysis showed a higher mortality rate among countries with a higher proportion of Caucasian populations and higher income levels.Conclusion: There is a lower ALS occurrence in Latin America compared to Europe and North America. This meta-analysis supports the hypothesis of a higher ALS risk among the Caucasian population. Further studies are needed to investigate the role of ancestral origins in ALS, taking socioeconomic status into consideration.},
}

Humans
Latin America/epidemiology
*Amyotrophic Lateral Sclerosis/epidemiology
Ethnicity
Caribbean Region
Europe

@article {pmid35179485,
year = {2022},
author = {Lidborg, LH and Cross, CP and Boothroyd, LG},
title = {A meta-analysis of the association between male dimorphism and fitness outcomes in humans.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35179485},
issn = {2050-084X},
mesh = {*Choice Behavior ; Female ; Humans ; Male ; Masculinity ; *Sex Characteristics ; Sexual Behavior ; Testosterone ; },
abstract = {Humans are sexually dimorphic: men and women differ in body build and composition, craniofacial structure, and voice pitch, likely mediated in part by developmental testosterone. Sexual selection hypotheses posit that, ancestrally, more 'masculine' men may have acquired more mates and/or sired more viable offspring. Thus far, however, evidence for either association is unclear. Here, we meta-analyze the relationships between six masculine traits and mating/reproductive outcomes (96 studies, 474 effects, N = 177,044). Voice pitch, height, and testosterone all predicted mating; however, strength/muscularity was the strongest and only consistent predictor of both mating and reproduction. Facial masculinity and digit ratios did not significantly predict either. There was no clear evidence for any effects of masculinity on offspring viability. Our findings support arguments that strength/muscularity may be sexually selected in humans, but cast doubt regarding selection for other forms of masculinity and highlight the need to increase tests of evolutionary hypotheses outside of industrialized populations.},
}

*Choice Behavior
Female
Humans
Male
Masculinity
*Sex Characteristics
Sexual Behavior
Testosterone

@article {pmid35169211,
year = {2022},
author = {Zhang, L and Tang, L and Huang, T and Fan, D},
title = {Association between type 2 diabetes and amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {2544},
pmid = {35169211},
issn = {2045-2322},
mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/*epidemiology ; Genome-Wide Association Study ; Humans ; },
abstract = {Type 2 diabetes (T2D) and amyotrophic lateral sclerosis (ALS) are associated consistently. However, it is currently unknown whether this association is causal. We aimed to estimate the unconfounded, causal association between T2D on ALS using a two-sample Mendelian randomization approach both in European and East Asian ancestry. Genetic variants strongly associated with T2D and each T2D markers were used to investigate the effect of T2D on ALS risk in European (involving 20,806 ALS cases and 59,804 controls) and East Asian (involving 1234 ALS cases and 2850 controls) ancestry. We found that the OR of ALS per 1 SD increase in T2D was estimated to be 0.96 [95% confidence interval (CI) 0.92-0.996; p = 0.03] in European populations. Similarly, all 8 SNPs were associated with T2D in East Asian ancestry, the OR of ALS per 1 SD increase in T2D was estimated to be 0.83 [95% CI 0.70-0.992; p = 0.04] in East Asian populations. Examining the intercept estimates from MR-Egger regression also leads to the same conclusion, in that horizontal pleiotropy unlikely influences the results in either population. We found that genetically predicted T2D was associated with significantly lower odds of amyotrophic lateral sclerosis both in European and East Asian populations. It is now critical to identify a clear molecular explanation for this association between T2D and ALS and to focus on its potential therapeutic implications.},
}

Amyotrophic Lateral Sclerosis/*epidemiology
Case-Control Studies
Diabetes Mellitus, Type 2/*epidemiology
Genome-Wide Association Study
Humans

@article {pmid34963663,
year = {2022},
author = {Ziff, OJ and Clarke, BE and Taha, DM and Crerar, H and Luscombe, NM and Patani, R},
title = {Meta-analysis of human and mouse ALS astrocytes reveals multi-omic signatures of inflammatory reactive states.},
journal = {Genome research},
volume = {32},
number = {1},
pages = {71-84},
pmid = {34963663},
issn = {1549-5469},
support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/L016311/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 103760/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Animals ; Astrocytes/metabolism ; Disease Models, Animal ; Humans ; *Induced Pluripotent Stem Cells ; Mice ; Mice, Transgenic ; Motor Neurons/metabolism ; Mutation ; },
abstract = {Astrocytes contribute to motor neuron death in amyotrophic lateral sclerosis (ALS), but whether they adopt deleterious features consistent with inflammatory reactive states remains incompletely resolved. To identify inflammatory reactive features in ALS human induced pluripotent stem cell (hiPSC)-derived astrocytes, we examined transcriptomics, proteomics, and glutamate uptake in VCP-mutant astrocytes. We complemented this by examining other ALS mutations and models using a systematic meta-analysis of all publicly-available ALS astrocyte sequencing data, which included hiPSC-derived astrocytes carrying SOD1, C9orf72, and FUS gene mutations as well as mouse ALS astrocyte models with SOD1[G93A] mutation, Tardbp deletion, and Tmem259 (also known as membralin) deletion. ALS astrocytes were characterized by up-regulation of genes involved in the extracellular matrix, endoplasmic reticulum stress, and the immune response and down-regulation of synaptic integrity, glutamate uptake, and other neuronal support processes. We identify activation of the TGFB, Wnt, and hypoxia signaling pathways in both hiPSC and mouse ALS astrocytes. ALS changes positively correlate with TNF, IL1A, and complement pathway component C1q-treated inflammatory reactive astrocytes, with significant overlap of differentially expressed genes. By contrasting ALS changes with models of protective reactive astrocytes, including middle cerebral artery occlusion and spinal cord injury, we uncover a cluster of genes changing in opposing directions, which may represent down-regulated homeostatic genes and up-regulated deleterious genes in ALS astrocytes. These observations indicate that ALS astrocytes augment inflammatory processes while concomitantly suppressing neuronal supporting mechanisms, thus resembling inflammatory reactive states and offering potential therapeutic targets.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Animals
Astrocytes/metabolism
Disease Models, Animal
Humans
*Induced Pluripotent Stem Cells
Mice
Mice, Transgenic
Motor Neurons/metabolism
Mutation

@article {pmid34874217,
year = {2022},
author = {Sferruzza, G and Bosco, L and Falzone, YM and Russo, T and Domi, T and Quattrini, A and Filippi, M and Riva, N},
title = {Neurofilament light chain as a biological marker for amyotrophic lateral sclerosis: a meta-analysis study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {5-6},
pages = {446-457},
doi = {10.1080/21678421.2021.2007952},
pmid = {34874217},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Enzyme-Linked Immunosorbent Assay ; Humans ; Intermediate Filaments ; Neurofilament Proteins ; },
abstract = {Aim: The aim of the present metanalysis is to evaluate blood and CSF Neurofilament light chain (NfL) concentrations in ALS patients, compared to healthy controls, ALS mimic disorders (ALSmd) and other neurological diseases (OND), and to evaluate their diagnostic yield against ALSmd. Methods: Search engines were systematically investigated for relevant studies. A random effect model was applied to estimate the pooled standard mean difference in NfL levels between ALS and controls and a bivariate mixed-effects model was applied to estimate their diagnostic accuracy on blood and CSF. Results and conclusions: NfL CSF levels were higher in ALS compared with all other control groups. On blood, NfL levels were significantly higher in ALS patients compared with healthy controls and ALSmd. In a subgroup analysis, the use of SIMOA yielded to a better differentiation between ALS and controls on blood, compared with ELISA. Studies performed on CSF (AUC = 0.90) yielded to better diagnostic performances compared with those conducted on blood (AUC = 0.78). Further prospective investigations are needed to determine a diagnostic cutoff, exploitable in clinical practice.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Biomarkers
Enzyme-Linked Immunosorbent Assay
Humans
Intermediate Filaments
Neurofilament Proteins

@article {pmid34864363,
year = {2021},
author = {Su, WM and Cheng, YF and Jiang, Z and Duan, QQ and Yang, TM and Shang, HF and Chen, YP},
title = {Predictors of survival in patients with amyotrophic lateral sclerosis: A large meta-analysis.},
journal = {EBioMedicine},
volume = {74},
number = {},
pages = {103732},
pmid = {34864363},
issn = {2352-3964},
mesh = {Amyotrophic Lateral Sclerosis/*mortality ; Female ; Humans ; Life Style ; Male ; Prognosis ; Risk Assessment ; Survival Analysis ; Young Adult ; },
abstract = {BACKGROUND: The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS.

METHODS: A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1[st] January 1966 to 1[st] December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923.

FINDINGS: A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival.

INTERPRETATION: Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS.

FUNDING: This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).},
}

Amyotrophic Lateral Sclerosis/*mortality
Female
Humans
Life Style
Male
Prognosis
Risk Assessment
Survival Analysis
Young Adult

@article {pmid34726989,
year = {2022},
author = {Shi, G and Shao, S and Zhou, J and Huang, K and Bi, FF},
title = {Urinary p75[ECD] levels in patients with amyotrophic lateral sclerosis: a meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {5-6},
pages = {438-445},
doi = {10.1080/21678421.2021.1990345},
pmid = {34726989},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Case-Control Studies ; Humans ; },
abstract = {Objective: p75 neurotrophin receptor (p75[NTR]) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75[NTR](p75[ECD]) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75[ECD] levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p = 0.008). Increased urinary p75[ECD] levels were inversely associated with ALSFRS-R in ALS patients (r = -0.32, 95% CI [-0.43, -0.21], p < 0.001). Conclusions: Given the associations between p75[ECD] and ALS found in this meta-analysis, urinary p75[ECD] levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Case-Control Studies
Humans

@article {pmid34502460,
year = {2021},
author = {Fernández-Beltrán, LC and Godoy-Corchuelo, JM and Losa-Fontangordo, M and Williams, D and Matias-Guiu, J and Corrochano, S},
title = {A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice.},
journal = {International journal of molecular sciences},
volume = {22},
number = {17},
pages = {},
pmid = {34502460},
issn = {1422-0067},
support = {2018-T1/BMD-10731//Consejería de Educación, Juventud y Deporte, Comunidad de Madrid/ ; },
mesh = {Amyotrophic Lateral Sclerosis/etiology/*metabolism ; Animals ; Disease Models, Animal ; Female ; *Lipid Metabolism ; Mice ; Spinal Cord/*metabolism ; Steroid Hydroxylases/genetics/metabolism ; *Transcriptome ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1[G93A] mice at an early disease stage, followed by a robust transcriptomic meta-analysis using publicly available RNA-seq data from the spinal cord of SOD1 mice at early and late symptomatic disease stages. The meta-analyses identified few lipid metabolic pathways dysregulated early that were exacerbated at symptomatic stages; mainly cholesterol biosynthesis, ceramide catabolism, and eicosanoid synthesis pathways. We present an insight into the pathological mechanisms in ALS, confirming that lipid metabolic alterations are transcriptionally dysregulated and are central to ALS aetiology, opening new options for the treatment of these devastating conditions.},
}

Amyotrophic Lateral Sclerosis/etiology/*metabolism
Animals
Disease Models, Animal
Female
*Lipid Metabolism
Mice
Spinal Cord/*metabolism
Steroid Hydroxylases/genetics/metabolism
*Transcriptome

@article {pmid34431799,
year = {2021},
author = {Mavroudis, I and Knights, M and Petridis, F and Chatzikonstantinou, S and Karantali, E and Kazis, D},
title = {Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis.},
journal = {Journal of clinical neuromuscular disease},
volume = {23},
number = {1},
pages = {31-38},
doi = {10.1097/CND.0000000000000353},
pmid = {34431799},
issn = {1537-1611},
mesh = {5'-Nucleotidase ; Autoantibodies ; Bayes Theorem ; Humans ; Male ; Muscle, Skeletal ; *Myositis ; *Myositis, Inclusion Body/diagnosis ; },
abstract = {Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5'-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.},
}

5'-Nucleotidase
Autoantibodies
Bayes Theorem
Humans
Male
Muscle, Skeletal
*Myositis
*Myositis, Inclusion Body/diagnosis

@article {pmid34397718,
year = {2021},
author = {Chang, MC and Kwak, SG and Park, JS and Park, D},
title = {Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis.},
journal = {Medicine},
volume = {100},
number = {30},
pages = {e26751},
pmid = {34397718},
issn = {1536-5964},
support = {NRF-2019M3E5D1A02068106//National Research Foundation of Korea grand funded by the Korean government/ ; },
mesh = {Amyotrophic Lateral Sclerosis/*chemically induced ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects ; },
abstract = {OBJECTIVE: Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence.

METHODS: A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis.

RESULTS: Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53-1.08]).

CONCLUSION: No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.},
}

Amyotrophic Lateral Sclerosis/*chemically induced
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects

@article {pmid33706058,
year = {2021},
author = {Haji, S and Sako, W and Murakami, N and Osaki, Y and Furukawa, T and Izumi, Y and Kaji, R},
title = {The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis.},
journal = {Clinical neurology and neurosurgery},
volume = {203},
number = {},
pages = {106566},
doi = {10.1016/j.clineuro.2021.106566},
pmid = {33706058},
issn = {1872-6968},
mesh = {Amyotrophic Lateral Sclerosis/*blood/*diagnosis ; Biomarkers/blood ; Humans ; Prognosis ; Sensitivity and Specificity ; Uric Acid/*blood ; },
abstract = {OBJECTIVE: To determine the value of uric acid (UA) as a prognostic biomarker for amyotrophic lateral sclerosis (ALS) using a meta-analysis of hazard ratio-based studies.

METHODS: We included data from Tokushima University (47 patients with ALS) and three previous studies (1835 patients with ALS) with a hazard ratio (HR) identified by a systematic computational search. A total of four studies and 1882 patients were enrolled in the pooled analysis. We pooled HRs of death or tracheostomy, which were estimated by a Cox proportional hazard model, using a random-effects model. Heterogeneity was assessed by Q statistic, and a p value < 0.1 was considered significant heterogeneity. Furthermore, sensitivity analysis was performed to assess the effect of each single study and the robustness of the summary effect. We evaluated publication bias by visual assessment of the funnel plot and Egger's test, and adjusted the bias using a trim-and-fill method.

RESULTS: This meta-analysis revealed that UA could be a prognostic factor for ALS (all, HR = 0.87, p < 0.001; men, HR = 0.83, p < 0.001; women, HR = 0.76, p < 0.001). The included studies were homogeneous (all, p = 0.43; men, p = 0.9; women, p = 0.49). Sensitivity analysis confirmed the robustness of these summary effects. Publication bias was detected, which was adjusted for by a trim-and-fill method. The adjusted results showed significant summary effects (all, HR = 0.88, p = 0.002; men, HR = 0.83, p < 0.001; women, HR = 0.77, p < 0.001).

CONCLUSION: The present meta-analysis suggests that the serum UA level could be a prognostic biomarker in patients with ALS. Sensitivity analyses and the trim-and-fill method supported the robustness of these results.},
}

Amyotrophic Lateral Sclerosis/*blood/*diagnosis
Biomarkers/blood
Humans
Prognosis
Sensitivity and Specificity
Uric Acid/*blood

@article {pmid33678061,
year = {2021},
author = {Spielmans, GI},
title = {Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women.},
journal = {Journal of sex research},
volume = {58},
number = {9},
pages = {1085-1105},
doi = {10.1080/00224499.2021.1885601},
pmid = {33678061},
issn = {1559-8519},
mesh = {Female ; Humans ; *Libido ; Peptides, Cyclic ; *Sexual Dysfunctions, Psychological/drug therapy ; alpha-MSH ; },
abstract = {Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.},
}

Female
Humans
*Libido
Peptides, Cyclic
*Sexual Dysfunctions, Psychological/drug therapy
alpha-MSH

@article {pmid33199452,
year = {2020},
author = {Shoesmith, C and Abrahao, A and Benstead, T and Chum, M and Dupre, N and Izenberg, A and Johnston, W and Kalra, S and Leddin, D and O'Connell, C and Schellenberg, K and Tandon, A and Zinman, L},
title = {Canadian best practice recommendations for the management of amyotrophic lateral sclerosis.},
journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne},
volume = {192},
number = {46},
pages = {E1453-E1468},
pmid = {33199452},
issn = {1488-2329},
mesh = {Amyotrophic Lateral Sclerosis/*therapy ; Canada ; Humans ; *Patient Care Team ; Societies, Medical ; },
}

Amyotrophic Lateral Sclerosis/*therapy
Canada
Humans
*Patient Care Team
Societies, Medical

@article {pmid33113361,
year = {2020},
author = {Iacoangeli, A and Lin, T and Al Khleifat, A and Jones, AR and Opie-Martin, S and Coleman, JRI and Shatunov, A and Sproviero, W and Williams, KL and Garton, F and Restuadi, R and Henders, AK and Mather, KA and Needham, M and Mathers, S and Nicholson, GA and Rowe, DB and Henderson, R and McCombe, PA and Pamphlett, R and Blair, IP and Schultz, D and Sachdev, PS and Newhouse, SJ and Proitsi, P and Fogh, I and Ngo, ST and Dobson, RJB and Wray, NR and Steyn, FJ and Al-Chalabi, A},
title = {Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.},
journal = {Cell reports},
volume = {33},
number = {4},
pages = {108323},
pmid = {33113361},
issn = {2211-1247},
support = {ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_PC_17214/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; ALCHALABI-TALBOT/APR14/926-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {Acyltransferases/*adverse effects ; Amyotrophic Lateral Sclerosis/*complications/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study/*methods ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Weight Loss/*genetics ; },
abstract = {We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10[-9]), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.},
}

Acyltransferases/*adverse effects
Amyotrophic Lateral Sclerosis/*complications/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study/*methods
Humans
Polymorphism, Single Nucleotide/*genetics
Weight Loss/*genetics

@article {pmid32968195,
year = {2020},
author = {Nakamura, R and Misawa, K and Tohnai, G and Nakatochi, M and Furuhashi, S and Atsuta, N and Hayashi, N and Yokoi, D and Watanabe, H and Watanabe, H and Katsuno, M and Izumi, Y and Kanai, K and Hattori, N and Morita, M and Taniguchi, A and Kano, O and Oda, M and Shibuya, K and Kuwabara, S and Suzuki, N and Aoki, M and Ohta, Y and Yamashita, T and Abe, K and Hashimoto, R and Aiba, I and Okamoto, K and Mizoguchi, K and Hasegawa, K and Okada, Y and Ishihara, T and Onodera, O and Nakashima, K and Kaji, R and Kamatani, Y and Ikegawa, S and Momozawa, Y and Kubo, M and Ishida, N and Minegishi, N and Nagasaki, M and Sobue, G},
title = {A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.},
journal = {Communications biology},
volume = {3},
number = {1},
pages = {526},
pmid = {32968195},
issn = {2399-3642},
mesh = {Amyotrophic Lateral Sclerosis/ethnology/*genetics ; Asian People/genetics ; Case-Control Studies ; China ; Coenzyme A Ligases/*genetics/physiology ; Female ; Genes/*genetics ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Japan ; Male ; Polymorphism, Single Nucleotide/genetics ; White People/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10[-8]). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10[-4]). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10[-11]). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.},
}

Amyotrophic Lateral Sclerosis/ethnology/*genetics
Asian People/genetics
Case-Control Studies
China
Coenzyme A Ligases/*genetics/physiology
Female
Genes/*genetics
Genetic Predisposition to Disease/*genetics
Genome-Wide Association Study
Humans
Japan
Male
Polymorphism, Single Nucleotide/genetics
White People/genetics

@article {pmid32901053,
year = {2020},
author = {Chang, MC and Kwak, SG and Park, JS and Park, D},
title = {The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {14759},
pmid = {32901053},
issn = {2045-2322},
mesh = {Acetaminophen/*therapeutic use ; Amyotrophic Lateral Sclerosis/metabolism/pathology/*prevention & control ; Analgesics, Non-Narcotic/*therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Drug Therapy, Combination ; Humans ; },
abstract = {To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90-1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73-0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69-0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.},
}

Acetaminophen/*therapeutic use
Amyotrophic Lateral Sclerosis/metabolism/pathology/*prevention & control
Analgesics, Non-Narcotic/*therapeutic use
Animals
Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
Drug Therapy, Combination
Humans

@article {pmid32651855,
year = {2021},
author = {Yang, B and Yang, C and Ren, J and Zhong, C and Liu, K and Zhao, L and Li, L and Wang, H and Zhu, M and Lin, Z},
title = {Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {42},
number = {2},
pages = {625-631},
pmid = {32651855},
issn = {1590-3478},
support = {20YYJC0146//Sichuan application basic research project/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Asian People ; Case-Control Studies ; Genome-Wide Association Study ; Humans ; Mitochondrial Proteins/genetics ; White People ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS.

METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed.

RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201).

CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.},
}

*Amyotrophic Lateral Sclerosis/epidemiology/genetics
Asian People
Case-Control Studies
Genome-Wide Association Study
Humans
Mitochondrial Proteins/genetics
White People

@article {pmid32028381,
year = {2020},
author = {Lenoir, D and De Pauw, R and Van Oosterwijck, S and Cagnie, B and Meeus, M},
title = {Acupuncture Versus Sham Acupuncture: A Meta-Analysis on Evidence for Longer-term Effects of Acupuncture in Musculoskeletal Disorders.},
journal = {The Clinical journal of pain},
volume = {36},
number = {7},
pages = {533-549},
doi = {10.1097/AJP.0000000000000812},
pmid = {32028381},
issn = {1536-5409},
mesh = {*Acupuncture Therapy ; Humans ; *Musculoskeletal Diseases/therapy ; Pain ; Quality of Life ; },
abstract = {EDITORIAL NOTE: The original Letter to the Editor prepared by Jones et al was based on the initial electronic version then contained several important procedural errors that resulted in erroneous conclusions as noted by Jones et al in their original Letter. Subsequently, the authors of the Letter to the Editor were notified of the corrections and they then prepared the revised Letter to the Editor published here. Jones et al did note a remaining error in Table 5 of their corrected manuscript. Based on Jones et al's observation, Lenoir et al were notified of an error on Table 5 and have addressed this in the current version of their paper published in this issue. We appreciate the input of the authors of the letter and the positive response of the author(s) of this article. Dennis C. Turk, PhD Editor-in-Chief OBJECTIVE:: Acupuncture is a common modality in the therapy of musculoskeletal disorders. The evidence for acupuncture has been examined frequently, but a clear synthesis of previous research is currently lacking. This meta-analysis aimed to summarize the evidence for nonimmediate effects of acupuncture on pain, functionality, and quality of life in patients with musculoskeletal disorders, when compared with sham acupuncture.

METHODS: Search results from PubMed and Web of Science were brought together. All screening procedures were executed twice by 2 independent researchers. The pooled standardized mean difference (SMD) with its confidence interval (CI) was estimated at follow-up at <1 month, 1 to 3 months, 3 to 6 months, and >6 months.

RESULTS: For pain, the SMD equalled respectively -0.47 (CI -0.76 to -0.19), -0.27 (CI -0.44 to -0.11), -0.32 (CI -0.51 to -0.13) and -0.12 (CI -0.36 to 0.11) for <1 month, 1 to 3 months, 3 to 6 months, and >6 months follow-up. For functionality, the pooled SMD equalled -0.43 (CI -0.76 to -0.10), -0.41 (CI -0.76 to -0.05), 0.07 (CI -0.22 to 0.36), and -0.13 (-0.46 to 0.19). In the area of QOL, pooled SMD of respectively 0.20 (CI 0.04 to 0.35), 0.19 (CI -0.01 to 0.39), 0.02 (CI -0.09 to 0.14) and -0.04 (CI -0.25 to 0.16) were obtained.

DISCUSSION: A significant difference in therapy effect, favoring acupuncture, was found for pain at <1 month, 1 to 3 months, and 3 to 6 months, as well as on quality of life at <1 month, and on functionality at <1 month and 1 to 3 months.},
}

*Acupuncture Therapy
Humans
*Musculoskeletal Diseases/therapy
Pain
Quality of Life

@article {pmid31932031,
year = {2020},
author = {Corcia, P and Lumbroso, S and Cazeneuve, C and Mouzat, K and Camu, W and Vourc'h, P and , },
title = {Pre-symptomatic diagnosis in ALS.},
journal = {Revue neurologique},
volume = {176},
number = {3},
pages = {166-169},
doi = {10.1016/j.neurol.2019.07.027},
pmid = {31932031},
issn = {0035-3787},
mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology/*genetics ; Asymptomatic Diseases ; Confidentiality/standards ; DNA Mutational Analysis/methods/standards ; Disclosure/standards ; Early Diagnosis ; Gene Frequency ; Genetic Association Studies ; Genetic Counseling/methods/standards ; Genetic Predisposition to Disease ; Genetic Testing/methods/*standards ; Humans ; Molecular Diagnostic Techniques/methods/standards ; Prodromal Symptoms ; },
abstract = {Pathophysiology of amyotrophic lateral sclerosis (ALS) remains partially understood even though it is accepted worldwide that motor neuron death results from a pluri-factorial process with a variable role of genetic factors. Although not distinguishable from a clinical point of view, familial forms of ALS (fALS, 10% of cases) and sporadic forms (sALS, 90% of cases) can be described. Since the identification of superoxide dismutase 1 gene (SOD1) mutations, more than 30 genes have been linked to fALS. Among these genes, five (C9ORF72, SOD1, TARDBP, FUS, TBK1) seem predominant with mutation frequencies of 40%, 20%, 5%, <5%, <5% in fALS and 6%, 3%, and <1% for the last three in sALS, respectively. The situation that classically leads to request genetic screening is the presence of a familial history of motor neuron disorders (MND) or fronto-temporal lobar dementia (FTLD). However, this dichotomy between fALS and sALS based on familial history can lead to mistakes since illegitimacy, ignorance of MND, FTD or psychiatric disorders within the family due to a familial censorship or lack of familial relationship, or a recessive autosomal inheritance could wrongly lead to failing to recognize a familial form. The significant development of genetic research and easier access to genetic tests in fALS increase the number of situations for which gene mutations are identified. The consequence is an increase in genetic requests from relatives of ALS patients who are eager to know their own genetic status and their own individual risk to develop ALS. Pre-symptomatic testing is thus becoming a daily issue in ALS Centers. This led us to propose a framework for such pre-symptomatic genetic testing for people at risk for developing ALS.},
}

Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology/*genetics
Asymptomatic Diseases
Confidentiality/standards
DNA Mutational Analysis/methods/standards
Disclosure/standards
Early Diagnosis
Gene Frequency
Genetic Association Studies
Genetic Counseling/methods/standards
Genetic Predisposition to Disease
Genetic Testing/methods/*standards
Humans
Molecular Diagnostic Techniques/methods/standards
Prodromal Symptoms

@article {pmid31673225,
year = {2019},
author = {Xu, C and Wu, J and Wang, J},
title = {Associations of rs524952 and rs634990 gene polymorphisms in 15q14 with high myopia: A meta-analysis.},
journal = {Molecular vision},
volume = {25},
number = {},
pages = {603-609},
pmid = {31673225},
issn = {1090-0535},
mesh = {Adult ; Chromosomes, Human, Pair 15/*genetics ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Middle Aged ; Models, Genetic ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; Risk Factors ; Young Adult ; },
abstract = {PURPOSE: Many studies have been conducted to investigate the association between the rs524952 and rs634990 polymorphisms and high myopia (HM). However, the results were conflicting. Thus, a meta-analysis was needed to reveal the real association between the two single nucleotide polymorphisms (SNPs) and HM.

METHODS: All eligible studies published in Pubmed, Embase, China Biologic Medicine (CBM), the China National Knowledge Infrastructure (CNKI), the Cochrane Library, and the Web of Science from 2010 to March 2019 were examined.

RESULTS: Six comparison groups in four studies with 5,293 subjects for the rs524952 polymorphism and five studies with 6,750 subjects for the rs634990 polymorphism were included. No statistically significant associations were observed between the rs524952 and rs634990 polymorphisms and HM under the allelic model, recessive genetic model, and dominant genetic model in this meta-analysis. Subgroup analysis was conducted by dividing the studies into two groups according to the case sample size, which showed that the association between the rs524952 polymorphism and HM was found only in a subgroup of fewer than 300 cases under the dominant genetic model (OR=0.64; 95% confidence interval [CI]:0.43-0.96). Sensitivity analysis for the rs524952 polymorphism suggested the results of this study were stable under all the genetic models. However, the association between the rs634990 polymorphism and HM turned out to be statistically significant in the allelic, recessive, and dominant genetic models after the omission of Qiang et al.'s study. No publication bias was found.

CONCLUSIONS: The results of this meta-analysis suggested the rs524952 and rs634990 polymorphisms may have nothing to do with the development of HM. The present results must be confirmed with larger-scale studies in the future.},
}

Adult
Chromosomes, Human, Pair 15/*genetics
*Genetic Association Studies
*Genetic Predisposition to Disease
Humans
Middle Aged
Models, Genetic
Myopia/*genetics
Polymorphism, Single Nucleotide/*genetics
Publication Bias
Risk Factors
Young Adult

@article {pmid31610740,
year = {2020},
author = {Zuckerman, M and Li, C and Lin, S and Hall, JA},
title = {The Negative Intelligence-Religiosity Relation: New and Confirming Evidence.},
journal = {Personality & social psychology bulletin},
volume = {46},
number = {6},
pages = {856-868},
doi = {10.1177/0146167219879122},
pmid = {31610740},
issn = {1552-7433},
mesh = {Adult ; Cognition ; Educational Status ; Female ; Humans ; *Intelligence ; Male ; *Religion ; },
abstract = {Zuckerman et al. (2013) conducted a meta-analysis of 63 studies that showed a negative intelligence-religiosity relation (IRR). As more studies have become available and because some of Zuckerman et al.'s (2013) conclusions have been challenged, we conducted a new meta-analysis with an updated data set of 83 studies. Confirming previous conclusions, the new analysis showed that the correlation between intelligence and religious beliefs in college and noncollege samples ranged from -.20 to -.23. There was no support for mediation of the IRR by education but there was support for partial mediation by analytic cognitive style. Thus, one possible interpretation for the IRR is that intelligent people are more likely to use analytic style (i.e., approach problems more rationally). An alternative (and less interesting) reason for the mediation is that tests of both intelligence and analytic style assess cognitive ability. Additional empirical and theoretical work is needed to resolve this issue.},
}

Adult
Cognition
Educational Status
Female
Humans
*Intelligence
Male
*Religion

@article {pmid31286297,
year = {2019},
author = {Corrado, L and Brunetti, M and Di Pierro, A and Barberis, M and Croce, R and Bersano, E and De Marchi, F and Zuccalà, M and Barizzone, N and Calvo, A and Moglia, C and Mazzini, L and Chiò, A and D'Alfonso, S},
title = {Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {40},
number = {12},
pages = {2537-2540},
pmid = {31286297},
issn = {1590-3478},
support = {FGBR17/2013//Arisla/ ; RF-2013-02355764//Ministero della Salute/ ; RF-2010-2309849//Ministero della Salute/ ; prin 2015//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Joint Programme - Neurodegenerative Disease Research (Strength and Brain-Mend projects)//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; FP7/2007-2013 under grant agreement 259867//FP7 Ideas: European Research Council/ ; },
mesh = {Amyotrophic Lateral Sclerosis/*genetics ; C9orf72 Protein/*genetics ; Cohort Studies ; Genes, Modifier/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Italy ; Membrane Proteins/*genetics ; Trinucleotide Repeat Expansion ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeat expansion in C9orf72 gene (C9orf72-HRE) is the most frequent genetic cause of ALS. Since many ALS pedigrees showed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72-HRE patients with contrasting findings. To disclose the possible role of NIPA1 GCG repeat length as modifier of the disease risk in C9orf72-HRE carriers, we analyzed a large cohort of 532 Italian ALS cases enriched in C9orf72-HRE carriers (172 cases) and 483 Italian controls. This sample size is powered (92% power, p = 0.05) to replicate the modifier effect observed in literature. We did not observe higher frequency of NIPA1 long alleles (> 8 GCG) in C9orf72-HRE carriers (3.5%) compared with C9orf72-HRE negative patients (4.1%) and healthy controls (5%). For the latter comparison, we meta-analyzed our data with currently available literature data, and no statistically significant effect was observed (p = 0.118). In conclusion, we did not confirm a role of NIPA1 repeat length as a modifier of the C9orf72 ALS disease risk.},
}

Amyotrophic Lateral Sclerosis/*genetics
C9orf72 Protein/*genetics
Cohort Studies
Genes, Modifier/*genetics
Genetic Predisposition to Disease/*genetics
Humans
Italy
Membrane Proteins/*genetics
Trinucleotide Repeat Expansion

@article {pmid31201598,
year = {2019},
author = {Yang, B and Jiang, H and Wang, F and Li, S and Wu, C and Bao, J and Zhu, Y and Xu, Z and Liu, B and Ren, H and Yang, X},
title = {UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {40},
number = {11},
pages = {2293-2302},
pmid = {31201598},
issn = {1590-3478},
support = {201801CH00572//Applied Basic Research Key Project of Yunnan (CN)/ ; 2018NS0102//Applied Basic Research Key Project of Yunnan (CN)/ ; 81860247//National Natural Science Foundation of China/ ; 2017BS005//Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas (BR)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/ethnology/genetics/mortality ; *Genetic Predisposition to Disease/epidemiology/ethnology/genetics ; Humans ; Nerve Tissue Proteins/*genetics ; Risk ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival.

METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed.

RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001).

CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.},
}

*Amyotrophic Lateral Sclerosis/ethnology/genetics/mortality
*Genetic Predisposition to Disease/epidemiology/ethnology/genetics
Humans
Nerve Tissue Proteins/*genetics
Risk

@article {pmid31020811,
year = {2019},
author = {Apolloni, S and Amadio, S and Fabbrizio, P and Morello, G and Spampinato, AG and Latagliata, EC and Salvatori, I and Proietti, D and Ferri, A and Madaro, L and Puglisi-Allegra, S and Cavallaro, S and Volonté, C},
title = {Histaminergic transmission slows progression of amyotrophic lateral sclerosis.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {10},
number = {4},
pages = {872-893},
pmid = {31020811},
issn = {2190-6009},
mesh = {Amyotrophic Lateral Sclerosis/*drug therapy/genetics ; Animals ; Disease Models, Animal ; Disease Progression ; Gene Expression/*genetics ; Histamine/pharmacology/*therapeutic use ; Humans ; Mice ; },
abstract = {BACKGROUND: Histamine is an immune modulator, neuroprotective, and remyelinating agent, beneficially acting on skeletal muscles and promoting anti-inflammatory features in amyotrophic lateral sclerosis (ALS) microglia. Drugs potentiating the endogenous release of histamine are in trial for neurological diseases, with a role not systematically investigated in ALS. Here, we examine histamine pathway associations in ALS patients and the efficacy of a histamine-mediated therapeutic strategy in ALS mice.

METHODS: We adopted an integrative multi-omics approach combining gene expression profiles, copy number variants, and single nucleotide polymorphisms of ALS patients. We treated superoxide dismutase 1 (SOD1)-G93A mice that recapitulate key ALS features, with the brain-permeable histamine precursor histidine in the symptomatic phase of the disease and analysed the rescue from disease pathological signs. We examined the action of histamine in cultured SOD1-G93A motor neuron-like cells.

RESULTS: We identified 13 histamine-related genes deregulated in the spinal cord of two ALS patient subgroups, among which genes involved in histamine metabolism, receptors, transport, and secretion. Some histamine-related genes overlapped with genomic regions disrupted by DNA copy number and with ALS-linked pathogenic variants. Histidine treatment in SOD1-G93A mice proved broad efficacy in ameliorating ALS features, among which most importantly lifespan, motor performance, microgliosis, muscle atrophy, and motor neurons survival in vivo and in vitro.

CONCLUSIONS: Our gene set/pathway enrichment analyses and preclinical studies started at the onset of symptoms establish that histamine-related genes are modifiers in ALS, supporting their role as candidate biomarkers and therapeutic targets. We disclose a novel important role for histamine in the characterization of the multi-gene network responsible for ALS and, furthermore, in the drug development process.},
}

Amyotrophic Lateral Sclerosis/*drug therapy/genetics
Animals
Disease Models, Animal
Disease Progression
Gene Expression/*genetics
Histamine/pharmacology/*therapeutic use
Humans
Mice

@article {pmid30982356,
year = {2019},
author = {Palumbo, JM and Hubble, J and Apple, S and Takei, K and Tsuda, K and Liu, S and Zhang, J and Agnese, W},
title = {Post-hoc analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {20},
number = {5-6},
pages = {421-431},
doi = {10.1080/21678421.2019.1599955},
pmid = {30982356},
issn = {2167-9223},
mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*drug therapy ; Clinical Trials, Phase II as Topic/*methods ; Clinical Trials, Phase III as Topic/*methods ; Disease Progression ; Double-Blind Method ; Edaravone/*therapeutic use ; Humans ; Neuroprotective Agents/*therapeutic use ; Randomized Controlled Trials as Topic/*methods ; Treatment Outcome ; },
abstract = {Objectives: The edaravone development program established a study design in which a treatment effect slowing functional loss in amyotrophic lateral sclerosis (ALS) could be documented within a 24-week time frame. This report elucidates the strategic enrichment design utilized to create efficiency and precision in the development program. Methods: Post-hoc analyses describe learning, sequential iteration, and evolution in study design. Results: The first Phase 3 study of edaravone in ALS (Study MCI186-16) included a large proportion (35%) of placebo patients who were minimal progressors. These patients demonstrated high heterogeneity in change in ALSFRS-R score (-4 median with interquartile range [IQR] 7.5) and a modal distribution score of 0, suggesting evidence of minimal change in ALSFRS-R during the study. This level of variability and rate of progression may have made it difficult to detect a prospective treatment effect in the study. A strategic enrichment strategy provided the second Phase 3 study (Study MCI186-19) with the ability to detect a treatment effect. In Study MCI186-19, only 13% of the placebo patients were minimal progressors. Further, these placebo patients demonstrated less heterogeneity and greater functional progression of ALS, thereby providing greater likelihood of detecting a treatment effect. The enrichment strategy may have excluded some rapidly progressing patients, potentially supporting the detection of a treatment effect. As previously published, Study MCI186-19 prospectively documented a 33% reduction in rate of progression of ALS (p = 0.0013). Conclusions: Strategic choices in the design of Study MCI186-19 reduced the proportion of minimally progressing patients and supported detection of a treatment effect.},
}

Amyotrophic Lateral Sclerosis/*diagnosis/*drug therapy
Clinical Trials, Phase II as Topic/*methods
Clinical Trials, Phase III as Topic/*methods
Disease Progression
Double-Blind Method
Edaravone/*therapeutic use
Humans
Neuroprotective Agents/*therapeutic use
Randomized Controlled Trials as Topic/*methods
Treatment Outcome

@article {pmid30337677,
year = {2018},
author = {Gorges, M and Del Tredici, K and Dreyhaupt, J and Braak, H and Ludolph, AC and Müller, HP and Kassubek, J},
title = {Corticoefferent pathology distribution in amyotrophic lateral sclerosis: in vivo evidence from a meta-analysis of diffusion tensor imaging data.},
journal = {Scientific reports},
volume = {8},
number = {1},
pages = {15389},
pmid = {30337677},
issn = {2045-2322},
mesh = {Amyotrophic Lateral Sclerosis/*pathology ; Brain Mapping/*methods ; Case-Control Studies ; Cross-Sectional Studies ; Diffusion Tensor Imaging/*methods ; Disease Progression ; Humans ; Image Processing, Computer-Assisted/*methods ; Longitudinal Studies ; Pyramidal Tracts/*pathology ; },
abstract = {A sequential transaxonal disease spread of amyotrophic lateral sclerosis (ALS)-associated TDP-43 pathology in four stages has been defined by post-mortem data, which have been transferred to in vivo imaging by diffusion tensor imaging (DTI) studies. Here, we aimed to investigate whether DTI meta-data are consistent with this proposed pattern of progression in ALS. A systematic literature search using the search engines PubMed and Scopus yielded a total of 370 publications. Of these, 57 studies with cross-sectional data and 10 longitudinal studies of human whole-brain analyses of fractional anisotropy (FA) were included in the final data analysis. Statistical meta-analyses on coordinates of significant FA alterations were performed on a grand average alteration data set using a fixed-effect model. A widespread pattern of white matter impairment was identified from cross-sectional meta data (n = 2064 ALS patients vs. n = 1688 controls) and supported from longitudinal meta data (n = 266 ALS patients over 8 months). The results from cross-sectional meta-analyses corresponded to the brain regions and tract systems according to the sequential disease spread of ALS. Structural alterations in ALS patients vs. controls followed a power gradient, i.e., the most frequent alterations were observed along the corticospinal tract (CST, related to ALS stage 1), followed by frequent alterations along the corticorubral/-pontine tract (related to ALS stage 2), together with corticostriatal pathways (related to ALS stage 3), and, finally, alterations in the hippocampal regions adjacent to the proximal portion of the perforant path (related to ALS stage 4). The results from the DTI-based neuroimaging meta-analysis strongly support the model of the corticoefferent axonal disease progression in ALS and provides further in vivo evidence for the proposed staging scheme of ALS-associated pathology.},
}

Amyotrophic Lateral Sclerosis/*pathology
Brain Mapping/*methods
Case-Control Studies
Cross-Sectional Studies
Diffusion Tensor Imaging/*methods
Disease Progression
Humans
Image Processing, Computer-Assisted/*methods
Longitudinal Studies
Pyramidal Tracts/*pathology

@article {pmid30228876,
year = {2018},
author = {Duggan, M and Tressoldi, P},
title = {Predictive physiological anticipatory activity preceding seemingly unpredictable stimuli: An update of Mossbridge et al's meta-analysis.},
journal = {F1000Research},
volume = {7},
number = {},
pages = {407},
pmid = {30228876},
issn = {2046-1402},
mesh = {Bayes Theorem ; *Forecasting ; Humans ; *Physiological Phenomena ; Publication Bias ; Regression Analysis ; },
abstract = {Background: This is an update of the Mossbridge et al's meta-analysis related to the physiological anticipation preceding seemingly unpredictable stimuli which overall effect size was 0.21; 95% Confidence Intervals: 0.13 - 0.29 Methods: Nineteen new peer and non-peer reviewed studies completed from January 2008 to June 2018 were retrieved describing a total of 27 experiments and 36 associated effect sizes. Results: The overall weighted effect size, estimated with a frequentist multilevel random model, was: 0.28; 95% Confidence Intervals: 0.18-0.38; the overall weighted effect size, estimated with a multilevel Bayesian model, was: 0.28; 95% Credible Intervals: 0.18-0.38. The weighted mean estimate of the effect size of peer reviewed studies was higher than that of non-peer reviewed studies, but with overlapped confidence intervals: Peer reviewed: 0.36; 95% Confidence Intervals: 0.26-0.47; Non-Peer reviewed: 0.22; 95% Confidence Intervals: 0.05-0.39. Similarly, the weighted mean estimate of the effect size of Preregistered studies was higher than that of Non-Preregistered studies: Preregistered: 0.31; 95% Confidence Intervals: 0.18-0.45; No-Preregistered: 0.24; 95% Confidence Intervals: 0.08-0.41. The statistical estimation of the publication bias by using the Copas selection model suggest that the main findings are not contaminated by publication bias. Conclusions: In summary, with this update, the main findings reported in Mossbridge et al's meta-analysis, are confirmed.},
}

Bayes Theorem
*Forecasting
Humans
*Physiological Phenomena
Publication Bias
Regression Analysis

@article {pmid30035009,
year = {2018},
author = {Zhang, F and Chen, G and He, M and Dai, J and Shang, H and Gong, Q and Jia, Z},
title = {Altered white matter microarchitecture in amyotrophic lateral sclerosis: A voxel-based meta-analysis of diffusion tensor imaging.},
journal = {NeuroImage. Clinical},
volume = {19},
number = {},
pages = {122-129},
pmid = {30035009},
issn = {2213-1582},
mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*diagnostic imaging/physiopathology ; Anisotropy ; Corpus Callosum/pathology ; *Diffusion Tensor Imaging/methods ; Female ; Humans ; *Image Processing, Computer-Assisted/methods ; Internal Capsule/pathology ; Male ; Middle Aged ; Nerve Fibers, Myelinated/pathology ; Nerve Net/pathology ; Pyramidal Tracts/*pathology ; White Matter/*pathology ; },
abstract = {BACKGROUND: The results of recent diffusion tensor imaging (DTI) studies on amyotrophic lateral sclerosis (ALS) are inconclusive and controversial. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS.

METHODS: A systematic search was conducted for relevant studies that used voxel-wise analyses of WM microarchitecture in patients with ALS. Anisotropic effect size-signed differential mapping (AES-SDM) was applied to analyze fractional anisotropy (FA) differences between ALS patients and healthy controls. Meta-regression analysis was used to explore the effects of clinical characteristics on WM integrity in patients with ALS.

RESULTS: A total of 14 studies with 16 datasets that included 396 patients and 360 healthy controls were identified. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The largest cluster exhibited a peak coordinate in the left corona radiata, extending to the body and splenium of the corpus callosum, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus. The other cluster exhibited decreased FA in the right corticospinal tract that extended to the right cerebral peduncle. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Mean age and illness duration were not linearly correlated with the FA reductions.

CONCLUSIONS: This study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract but also includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter.},
}

Adult
Aged
Aged, 80 and over
Amyotrophic Lateral Sclerosis/*diagnostic imaging/physiopathology
Anisotropy
Corpus Callosum/pathology
*Diffusion Tensor Imaging/methods
Female
Humans
*Image Processing, Computer-Assisted/methods
Internal Capsule/pathology
Male
Middle Aged
Nerve Fibers, Myelinated/pathology
Nerve Net/pathology
Pyramidal Tracts/*pathology
White Matter/*pathology

@article {pmid29943172,
year = {2018},
author = {Trippas, D and Kellen, D and Singmann, H and Pennycook, G and Koehler, DJ and Fugelsang, JA and Dubé, C},
title = {Characterizing belief bias in syllogistic reasoning: A hierarchical Bayesian meta-analysis of ROC data.},
journal = {Psychonomic bulletin & review},
volume = {25},
number = {6},
pages = {2141-2174},
pmid = {29943172},
issn = {1531-5320},
mesh = {*Bayes Theorem ; Humans ; *Logic ; *ROC Curve ; *Thinking ; },
abstract = {The belief-bias effect is one of the most-studied biases in reasoning. A recent study of the phenomenon using the signal detection theory (SDT) model called into question all theoretical accounts of belief bias by demonstrating that belief-based differences in the ability to discriminate between valid and invalid syllogisms may be an artifact stemming from the use of inappropriate linear measurement models such as analysis of variance (Dube et al., Psychological Review, 117(3), 831-863, 2010). The discrepancy between Dube et al.'s, Psychological Review, 117(3), 831-863 (2010) results and the previous three decades of work, together with former's methodological criticisms suggests the need to revisit earlier results, this time collecting confidence-rating responses. Using a hierarchical Bayesian meta-analysis, we reanalyzed a corpus of 22 confidence-rating studies (N = 993). The results indicated that extensive replications using confidence-rating data are unnecessary as the observed receiver operating characteristic functions are not systematically asymmetric. These results were subsequently corroborated by a novel experimental design based on SDT's generalized area theorem. Although the meta-analysis confirms that believability does not influence discriminability unconditionally, it also confirmed previous results that factors such as individual differences mediate the effect. The main point is that data from previous and future studies can be safely analyzed using appropriate hierarchical methods that do not require confidence ratings. More generally, our results set a new standard for analyzing data and evaluating theories in reasoning. Important methodological and theoretical considerations for future work on belief bias and related domains are discussed.},
}

*Bayes Theorem
Humans
*Logic
*ROC Curve
*Thinking

@article {pmid29932266,
year = {2018},
author = {Nobili, F and Arbizu, J and Bouwman, F and Drzezga, A and Agosta, F and Nestor, P and Walker, Z and Boccardi, M and , },
title = {European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain [18] F-fluorodeoxyglucose positron emission tomography in neurodegenerative cognitive impairment and dementia: Delphi consensus.},
journal = {European journal of neurology},
volume = {25},
number = {10},
pages = {1201-1217},
doi = {10.1111/ene.13728},
pmid = {29932266},
issn = {1468-1331},
mesh = {Brain/*diagnostic imaging ; Cognitive Dysfunction/*diagnostic imaging ; Dementia/*diagnostic imaging ; Diagnosis, Differential ; *Fluorodeoxyglucose F18 ; Humans ; Neurodegenerative Diseases/*diagnostic imaging ; Nuclear Medicine ; Positron-Emission Tomography/*methods ; Sensitivity and Specificity ; },
abstract = {BACKGROUND AND PURPOSE: Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured.

METHODS: Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion.

RESULTS: Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline.

CONCLUSIONS: Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.},
}

Brain/*diagnostic imaging
Cognitive Dysfunction/*diagnostic imaging
Dementia/*diagnostic imaging
Diagnosis, Differential
*Fluorodeoxyglucose F18
Humans
Neurodegenerative Diseases/*diagnostic imaging
Nuclear Medicine
Positron-Emission Tomography/*methods
Sensitivity and Specificity

@article {pmid29687175,
year = {2018},
author = {Marin, B and Fontana, A and Arcuti, S and Copetti, M and Boumédiene, F and Couratier, P and Beghi, E and Preux, PM and Logroscino, G},
title = {Age-specific ALS incidence: a dose-response meta-analysis.},
journal = {European journal of epidemiology},
volume = {33},
number = {7},
pages = {621-634},
pmid = {29687175},
issn = {1573-7284},
mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*epidemiology ; Child ; Child, Preschool ; Humans ; Incidence ; Infant ; Internationality ; Middle Aged ; Young Adult ; },
abstract = {To evaluate the association between worldwide ALS incidence rates and age, using a dose-response meta-analysis. We reviewed Medline and Embase up to July 2016 and included all population-based studies of newly-diagnosed cases, using multiple sources for case ascertainment. A dose-response meta-analysis was performed. A meta-regression investigated potential sources of heterogeneity. Of 3254 articles identified in the literature, we included 41 incidence studies covering 42 geographical areas. Overall, the fit between observed and predicted age-specific rates was very good. The expected variation of ALS incidence with age was characterized, in each study, by a progressive increase in the incidence from the 40s leading to a peak in the 60s or 70s, followed by a sharp decrease. Cochran's Q test suggested a significant heterogeneity between studies. Overall, estimated patterns of ALS age-specific incidence (at which the peak was reached) were similar among subcontinents of Europe and North America: peak of ALS incidence ranged in these areas between 6.98 and 8.17/100,000 PYFU, which referred to age in the range 71.6-77.4 years. The relationship between age and ALS incidence appeared different for Eastern Asia which was characterized by a peak of ALS incidence at 2.20/100,000 PYFU around 75 years of age. This study confirms the consistency of the age-specific ALS incidence pattern within different subcontinents. Age-specific incidence appears lower in Eastern Asia as compared to Europe and North America.},
}

Adolescent
Adult
Age Distribution
Aged
Aged, 80 and over
Amyotrophic Lateral Sclerosis/*epidemiology
Child
Child, Preschool
Humans
Incidence
Infant
Internationality
Middle Aged
Young Adult

@article {pmid29408898,
year = {2018},
author = {Cui, F and Sun, L and Xiong, J and Li, J and Zhao, Y and Huang, X},
title = {Therapeutic effects of percutaneous endoscopic gastrostomy on survival in patients with amyotrophic lateral sclerosis: A meta-analysis.},
journal = {PloS one},
volume = {13},
number = {2},
pages = {e0192243},
pmid = {29408898},
issn = {1932-6203},
mesh = {Aged ; Amyotrophic Lateral Sclerosis/physiopathology/*surgery ; Endoscopy/*methods ; Female ; Gastrostomy/*methods ; Humans ; Male ; Middle Aged ; Survival Rate ; },
abstract = {Percutaneous endoscopic gastrostomy (PEG) is a method widely used for patients with amyotrophic lateral sclerosis (ALS); nevertheless, its effect on survival remains unclear. The purpose of this meta-analysis study was to determine the effects of PEG on survival in ALS patients. Relevant studies were retrieved from PubMed, EmBase, and the Cochrane Library databases, from inception to June 2017. Studies comparing PEG with other procedures in ALS patients were included. Odds ratios (ORs) in a random-effects model were used to assess the survival at different follow-up periods. Briefly, ten studies involving a total of 996 ALS patients were included. Summary ORs indicated that PEG administration was not associated with 30-day (OR = 1.59; 95%CI 0.93-2.71; P = 0.092), 10-month (OR = 1.25; 95%CI 0.72-2.17; P = 0.436), and 30-month (OR = 1.28; 95% CI 0.77-2.11; P = 0.338) survival rates, while they showed a beneficial effect in 20-month survival rate (OR = 1.97; 95%CI 1.21-3.21; P = 0.007). The survival rate was significantly prominent in reports published before 2005, and in studies with a retrospective design, sample size <100, mean age <60.0 years, and percentage male ≥50.0%. To sum up, these findings suggested that ALS patients administered with PEG had an increased 20-month survival rates, while there was no significant effect in 30-day, 10-month, and 30-month survival rates.},
}

Aged
Amyotrophic Lateral Sclerosis/physiopathology/*surgery
Endoscopy/*methods
Female
Gastrostomy/*methods
Humans
Male
Middle Aged
Survival Rate

@article {pmid29348425,
year = {2018},
author = {Zhang, F and Zhang, Q and Ke, Y and Hao, J and Lu, L and Lu, N and Chen, X},
title = {Serum uric acid levels in patients with amyotrophic lateral sclerosis: a meta-analysis.},
journal = {Scientific reports},
volume = {8},
number = {1},
pages = {1100},
pmid = {29348425},
issn = {2045-2322},
mesh = {Amyotrophic Lateral Sclerosis/*blood/diagnosis/mortality ; Biomarkers ; Case-Control Studies ; Cause of Death ; Humans ; Prognosis ; Publication Bias ; Uric Acid/*blood ; },
abstract = {The pathogenic mechanism of ALS remains unclear. However, increasing evidence has indicated that uric acid (UA) may play a protective role in the pathogenesis of ALS. The aim of this study was to evaluate the association between serum UA levels and ALS. A comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library was conducted up to 31st August, 2017, using keywords. A random-effects model or fixed-effects model was used to calculate the pooled estimate according to the inter-group heterogeneity. Finally, we indentified 8 case-control and 3 cohort studies. The results indicated that patients with ALS had significant decreased levels of serum UA compared to healthy controls (standardized mean difference (SMD) = -0.72, 95% CI [-0.98,-0.46], P < 0.001). Increased serum UA levels were associated with lower all-cause mortality risk among ALS patients (risk ratio (RR) = 0.70, 95% CI [0.57, 0.87], P = 0.001). To summarize, there is an inverse association between serum UA levels and risk of death among ALS patients. Randomized controlled trials with high quality are required to elucidate the role of UA on ALS.},
}

Amyotrophic Lateral Sclerosis/*blood/diagnosis/mortality
Biomarkers
Case-Control Studies
Cause of Death
Humans
Prognosis
Publication Bias
Uric Acid/*blood

@article {pmid29274834,
year = {2018},
author = {Burgos, R and Bretón, I and Cereda, E and Desport, JC and Dziewas, R and Genton, L and Gomes, F and Jésus, P and Leischker, A and Muscaritoli, M and Poulia, KA and Preiser, JC and Van der Marck, M and Wirth, R and Singer, P and Bischoff, SC},
title = {ESPEN guideline clinical nutrition in neurology.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {37},
number = {1},
pages = {354-396},
doi = {10.1016/j.clnu.2017.09.003},
pmid = {29274834},
issn = {1532-1983},
mesh = {Deglutition Disorders/diagnosis/diet therapy/physiopathology ; Humans ; *Nervous System Diseases/diagnosis/diet therapy/physiopathology ; *Nutrition Policy ; Nutritional Status ; Prognosis ; Stroke/diagnosis/diet therapy/physiopathology ; },
abstract = {Neurological diseases are frequently associated with swallowing disorders and malnutrition. Moreover, patients with neurological diseases are at increased risk of micronutrient deficiency and dehydration. On the other hand, nutritional factors may be involved in the pathogenesis of neurological diseases. Multiple causes for the development of malnutrition in patients with neurological diseases are known including oropharyngeal dysphagia, impaired consciousness, perception deficits, cognitive dysfunction, and increased needs. The present evidence- and consensus-based guideline addresses clinical questions on best medical nutrition therapy in patients with neurological diseases. Among them, management of oropharyngeal dysphagia plays a pivotal role. The guideline has been written by a multidisciplinary team and offers 88 recommendations for use in clinical practice for amyotrophic lateral sclerosis, Parkinson's disease, stroke and multiple sclerosis.},
}

Deglutition Disorders/diagnosis/diet therapy/physiopathology
Humans
*Nervous System Diseases/diagnosis/diet therapy/physiopathology
*Nutrition Policy
Nutritional Status
Prognosis
Stroke/diagnosis/diet therapy/physiopathology

@article {pmid29092835,
year = {2017},
author = {Grafton, B and MacLeod, C and Rudaizky, D and Holmes, EA and Salemink, E and Fox, E and Notebaert, L},
title = {Confusing procedures with process when appraising the impact of cognitive bias modification on emotional vulnerability[†].},
journal = {The British journal of psychiatry : the journal of mental science},
volume = {211},
number = {5},
pages = {266-271},
doi = {10.1192/bjp.bp.115.176123},
pmid = {29092835},
issn = {1472-1465},
mesh = {Affective Symptoms/*therapy ; Cognitive Behavioral Therapy/*methods ; Humans ; *Meta-Analysis as Topic ; *Psychotherapeutic Processes ; },
abstract = {If meta-analysis is to provide valuable answers, then it is critical to ensure clarity about the questions being asked. Here, we distinguish two important questions concerning cognitive bias modification research that are not differentiated in the meta-analysis recently published by Cristea et al (2015) in this journal: (1) do the varying procedures that investigators have employed with the intention of modifying cognitive bias, on average, significantly impact emotional vulnerability?; and (2) does the process of successfully modifying cognitive bias, on average, significantly impact emotional vulnerability? We reanalyse the data from Cristea et al to address this latter question. Our new analyses demonstrate that successfully modifying cognitive bias does significantly alter emotional vulnerability. We revisit Cristea et al's conclusions in light of these findings.},
}

Affective Symptoms/*therapy
Cognitive Behavioral Therapy/*methods
Humans
*Meta-Analysis as Topic
*Psychotherapeutic Processes

@article {pmid29080013,
year = {2017},
author = {Watanabe, Y and Watanabe, T},
title = {Meta-analytic evaluation of the association between head injury and risk of amyotrophic lateral sclerosis.},
journal = {European journal of epidemiology},
volume = {32},
number = {10},
pages = {867-879},
pmid = {29080013},
issn = {1573-7284},
support = {656161//Horizon 2020/International ; },
mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*epidemiology/etiology ; Craniocerebral Trauma/complications/*diagnosis/*epidemiology ; Female ; Humans ; Risk Assessment ; Risk Factors ; },
abstract = {Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21-1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01-1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84-1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.},
}

Amyotrophic Lateral Sclerosis/*diagnosis/*epidemiology/etiology
Craniocerebral Trauma/complications/*diagnosis/*epidemiology
Female
Humans
Risk Assessment
Risk Factors

@article {pmid28984793,
year = {2017},
author = {Liu, J and Lu, SY and Wang, YG and Wei, ZY and Zhang, HX},
title = {SPINK1 Gene is Significantly Associated With Pancreatitis: A Comprehensive Meta-Analysis.},
journal = {Pancreas},
volume = {46},
number = {10},
pages = {1373-1380},
doi = {10.1097/MPA.0000000000000947},
pmid = {28984793},
issn = {1536-4828},
mesh = {Case-Control Studies ; Genetic Predisposition to Disease/*genetics ; Humans ; Mutation ; Odds Ratio ; Pancreatitis/*genetics ; Trypsin Inhibitor, Kazal Pancreatic/*genetics ; },
abstract = {OBJECTIVES: This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias.

METHODS: MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted.

RESULTS: Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists.

CONCLUSIONS: The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis.},
}

Case-Control Studies
Genetic Predisposition to Disease/*genetics
Humans
Mutation
Odds Ratio
Pancreatitis/*genetics
Trypsin Inhibitor, Kazal Pancreatic/*genetics

@article {pmid28931804,
year = {2017},
author = {Benyamin, B and He, J and Zhao, Q and Gratten, J and Garton, F and Leo, PJ and Liu, Z and Mangelsdorf, M and Al-Chalabi, A and Anderson, L and Butler, TJ and Chen, L and Chen, XD and Cremin, K and Deng, HW and Devine, M and Edson, J and Fifita, JA and Furlong, S and Han, YY and Harris, J and Henders, AK and Jeffree, RL and Jin, ZB and Li, Z and Li, T and Li, M and Lin, Y and Liu, X and Marshall, M and McCann, EP and Mowry, BJ and Ngo, ST and Pamphlett, R and Ran, S and Reutens, DC and Rowe, DB and Sachdev, P and Shah, S and Song, S and Tan, LJ and Tang, L and van den Berg, LH and van Rheenen, W and Veldink, JH and Wallace, RH and Wheeler, L and Williams, KL and Wu, J and Wu, X and Yang, J and Yue, W and Zhang, ZH and Zhang, D and Noakes, PG and Blair, IP and Henderson, RD and McCombe, PA and Visscher, PM and Xu, H and Bartlett, PF and Brown, MA and Wray, NR and Fan, D},
title = {Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.},
journal = {Nature communications},
volume = {8},
number = {1},
pages = {611},
pmid = {28931804},
issn = {2041-1723},
support = {ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Amyotrophic Lateral Sclerosis/ethnology/*genetics ; Asian People/*genetics ; Australia ; China ; DNA-Binding Proteins/*genetics ; Genome-Wide Association Study ; Glutathione Peroxidase/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis, DNA ; White People/*genetics ; },
abstract = {Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10[-8]), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10[-3]). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.},
}

Amyotrophic Lateral Sclerosis/ethnology/*genetics
Asian People/*genetics
Australia
China
DNA-Binding Proteins/*genetics
Genome-Wide Association Study
Glutathione Peroxidase/*genetics
High-Throughput Nucleotide Sequencing
Humans
Sequence Analysis, DNA
White People/*genetics

@article {pmid28864407,
year = {2017},
author = {Tai, H and Cui, L and Shen, D and Li, D and Cui, B and Fang, J},
title = {Military service and the risk of amyotrophic lateral sclerosis: A meta-analysis.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {45},
number = {},
pages = {337-342},
doi = {10.1016/j.jocn.2017.08.035},
pmid = {28864407},
issn = {1532-2653},
mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; Female ; Humans ; Military Personnel/*statistics & numerical data ; Risk Factors ; },
abstract = {To explore the relationship between the risk of amyotrophic lateral sclerosis and exposure to overall military service, we conducted a search of articles relevant to military service and the risk of ALS that used human subjects and were published in English through 20 May 2016, using Ovid Medline and Embase databases. Studies specially investigating the risk of ALS for Gulf war veterans were excluded. Quality of the cohort and case-control studies was assessed according to the Newcastle-Ottawa Scale (NOS). Analysis of data and publication bias were performed with Review Manager 5.3. A total of 8 case-control studies and 3 cohort studies were included in the meta-analysis. Only two case-control studies were conducted in Japan, comparing to 9 studies conducted in Europe/USA. The NOS scores of all studies were ≥6/9. The risk of ALS was significantly increased in military personnel compared to non-military personnel (pooled OR=1.29, 95% CI: 1.08-1.54, by random-effects model), with a moderate heterogeneity (P=0.01, I[2]=55%) due to some studies with lower quality, conformed by subgroup and sensitivity analysis. The present meta-analysis supports a positive association between overall military service and the risk of ALS. Additional studies are needed to find out related factors influencing the ALS risk of veterans, especially by gender and for specific geographic regions such as Asia. That would also do some favor to explore the etiology and mechanism of ALS.},
}

Amyotrophic Lateral Sclerosis/*epidemiology
Female
Humans
Military Personnel/*statistics & numerical data
Risk Factors

@article {pmid28795874,
year = {2018},
author = {Yang, X and Li, S and Xing, D and Li, P and Li, C and Qi, L and Xu, Y and Ren, H},
title = {Lack of association between the P413L variant of chromogranin B and ALS risk or age at onset: a meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {19},
number = {1-2},
pages = {80-86},
doi = {10.1080/21678421.2017.1361444},
pmid = {28795874},
issn = {2167-9223},
mesh = {Age of Onset ; Amyotrophic Lateral Sclerosis/*genetics ; Asian People ; Case-Control Studies ; Chromogranin B/*genetics ; Female ; Gene Frequency/genetics ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Genotype ; Heterozygote ; Humans ; Male ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is thought to result from interaction of genetic and environmental risk factors. Whether the potentially functional exonic P413L variant in the chromogranin B gene influences ALS risk and age at onset is controversial.

METHOD: We meta-analysed or other studies assessing the association between the P413L variant and ALS risk or age at ALS onset indexed in Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases.

RESULTS: Five case-control studies were analysed, involving 2639 patients with sporadic ALS, 201 with familial ALS and 3381 controls. No association was detected between risk of either ALS type and the CT + TT genotype or T-allele of the P413L variant. Age at ALS onset was similar between carriers and non-carriers of the T-allele.

CONCLUSION: The available evidence suggests that the P413L variant of chromogranin B is not associated with ALS risk or age at ALS onset. These results should be validated in large, well-designed studies.},
}

Age of Onset
Amyotrophic Lateral Sclerosis/*genetics
Asian People
Case-Control Studies
Chromogranin B/*genetics
Female
Gene Frequency/genetics
*Genetic Predisposition to Disease
Genetic Testing/methods
Genotype
Heterozygote
Humans
Male
Polymorphism, Single Nucleotide/genetics

@article {pmid28427253,
year = {2017},
author = {Su, M and Guo, J and Huang, J},
title = {Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma.},
journal = {Clinical and molecular hepatology},
volume = {23},
number = {2},
pages = {138-146},
pmid = {28427253},
issn = {2287-285X},
mesh = {Alleles ; Carcinoma, Hepatocellular/complications/*diagnosis/genetics ; Case-Control Studies ; Databases, Factual ; Gene Frequency ; *Genetic Predisposition to Disease ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/complications/*diagnosis/virology ; Humans ; Kinesins/*genetics ; Liver Neoplasms/complications/*diagnosis/genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; },
abstract = {BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC.

METHODS: The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study.

RESULTS: The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.'s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent.

CONCLUSIONS: The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.},
}

Alleles
Carcinoma, Hepatocellular/complications/*diagnosis/genetics
Case-Control Studies
Databases, Factual
Gene Frequency
*Genetic Predisposition to Disease
Hepatitis B virus/isolation & purification
Hepatitis B, Chronic/complications/*diagnosis/virology
Humans
Kinesins/*genetics
Liver Neoplasms/complications/*diagnosis/genetics
Odds Ratio
Polymorphism, Single Nucleotide
Risk Factors

@article {pmid28236105,
year = {2017},
author = {Morello, G and Spampinato, AG and Conforti, FL and D'Agata, V and Cavallaro, S},
title = {Selection and Prioritization of Candidate Drug Targets for Amyotrophic Lateral Sclerosis Through a Meta-Analysis Approach.},
journal = {Journal of molecular neuroscience : MN},
volume = {61},
number = {4},
pages = {563-580},
pmid = {28236105},
issn = {1559-1166},
mesh = {Amyotrophic Lateral Sclerosis/drug therapy/*genetics/metabolism ; Animals ; Antioxidants/*pharmacology/therapeutic use ; Drug Discovery ; Humans ; Mice ; Molecular Targeted Therapy ; Motor Cortex/drug effects/metabolism ; Neuroprotective Agents/*pharmacology/therapeutic use ; Species Specificity ; Superoxide Dismutase/genetics/metabolism ; Transcriptome ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. Although several compounds have shown promising results in preclinical studies, their translation into clinical trials has failed. This clinical failure is likely due to the inadequacy of the animal models that do not sufficiently reflect the human disease. Therefore, it is important to optimize drug target selection by identifying those that overlap in human and mouse pathology. We have recently characterized the transcriptional profiles of motor cortex samples from sporadic ALS (SALS) patients and differentiated these into two subgroups based on differentially expressed genes, which encode 70 potential therapeutic targets. To prioritize drug target selection, we investigated their degree of conservation in superoxide dismutase 1 (SOD1) G93A transgenic mice, the most widely used ALS animal model. Interspecies comparison of our human expression data with those of eight different SOD1[G93A] datasets present in public repositories revealed the presence of commonly deregulated targets and related biological processes. Moreover, deregulated expression of the majority of our candidate targets occurred at the onset of the disease, offering the possibility to use them for an early and more effective diagnosis and therapy. In addition to highlighting the existence of common key drivers in human and mouse pathology, our study represents the basis for a rational preclinical drug development.},
}

Amyotrophic Lateral Sclerosis/drug therapy/*genetics/metabolism
Animals
Antioxidants/*pharmacology/therapeutic use
Drug Discovery
Humans
Mice
Molecular Targeted Therapy
Motor Cortex/drug effects/metabolism
Neuroprotective Agents/*pharmacology/therapeutic use
Species Specificity
Superoxide Dismutase/genetics/metabolism
Transcriptome

@article {pmid28187987,
year = {2017},
author = {Żur-Wyrozumska, K and Pera, J and Dziubek, A and Sado, M and Golenia, A and Słowik, A and Dziedzic, T},
title = {Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis.},
journal = {Neurologia i neurochirurgia polska},
volume = {51},
number = {2},
pages = {135-139},
doi = {10.1016/j.pjnns.2017.01.008},
pmid = {28187987},
issn = {0028-3843},
mesh = {Adult ; Aged ; *Alleles ; Amyotrophic Lateral Sclerosis/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Poland ; Polymorphism, Genetic/*genetics ; Risk ; },
abstract = {OBJECTIVE: Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population.

METHODS: We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System.

RESULTS: The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population.

CONCLUSION: Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population.},
}

Adult
Aged
*Alleles
Amyotrophic Lateral Sclerosis/*genetics
Female
Gene Frequency
Genetic Predisposition to Disease/*genetics
Genotype
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
Middle Aged
Poland
Polymorphism, Genetic/*genetics
Risk

@article {pmid28104502,
year = {2017},
author = {Margeta, MA and Kuo, AN and Proia, AD and Freedman, SF},
title = {Staying away from the optic nerve: a formula for modifying glaucoma drainage device surgery in pediatric and other small eyes.},
journal = {Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus},
volume = {21},
number = {1},
pages = {39-43.e1},
doi = {10.1016/j.jaapos.2016.09.027},
pmid = {28104502},
issn = {1528-3933},
mesh = {Adolescent ; Axial Length, Eye/pathology ; Child ; Child, Preschool ; *Decision Support Techniques ; Drainage/instrumentation ; Female ; Glaucoma/physiopathology/*surgery ; *Glaucoma Drainage Implants ; Humans ; Infant ; Infant, Newborn ; Intraocular Pressure/physiology ; Limbus Corneae/*pathology ; Male ; Microphthalmos/physiopathology/*surgery ; Optic Nerve/*pathology ; Prosthesis Implantation/*standards ; },
abstract = {PURPOSE: To provide guidelines for safe implantation of glaucoma drainage devices (GDDs) in small and pediatric eyes to avoid contact between the optic nerve (ON) and the posterior edge of the GDD plate.

METHODS: We developed a formula for calculating limbus-to-ON distance to estimate the available "real estate" for GDD placement in small eyes. The formula was validated using eyes of pediatric decedents undergoing clinical autopsy, with axial lengths (AL) of 15-24 mm. For each autopsy eye, we measured AL, anterior chamber depth, corneal diameter, and limbus-to-ON distances for the four eye quadrants. The main outcome measure was the degree of agreement between measured and calculated limbus-to-ON distances.

RESULTS: A total of 15 autopsy eyes were divided into derivation (n = 10) and validation (n = 5) groups. A formula was derived to estimate superotemporal limbus-to-ON distance (DST) using AL and corneal diameter data. Linear regression showed excellent correlation between the measured DST and AL (R[2] = 0.98). There was excellent agreement between measured and calculated limbus-to-ON values for all four eye quadrants (R[2] range, 0.92-0.98).

CONCLUSIONS: Our formula accurately predicts limbus-to-ON distances across a wide range of clinically relevant ALs. Based on this information, GDD surgery in small eyes can be adjusted by positioning the GDD closer to the limbus or by trimming the posterior edge of the GDD plate. To our knowledge, this is the first set of guidelines developed to promote safe implantation of GDDs in small eyes.},
}

Adolescent
Axial Length, Eye/pathology
Child
Child, Preschool
*Decision Support Techniques
Drainage/instrumentation
Female
Glaucoma/physiopathology/*surgery
*Glaucoma Drainage Implants
Humans
Infant
Infant, Newborn
Intraocular Pressure/physiology
Limbus Corneae/*pathology
Male
Microphthalmos/physiopathology/*surgery
Optic Nerve/*pathology
Prosthesis Implantation/*standards

@article {pmid28004338,
year = {2018},
author = {Monti, C and Colugnat, I and Lopiano, L and Chiò, A and Alberio, T},
title = {Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.},
journal = {Molecular neurobiology},
volume = {55},
number = {1},
pages = {370-381},
pmid = {28004338},
issn = {1559-1182},
mesh = {Animals ; *Databases, Genetic/trends ; Gene Regulatory Networks/*physiology ; Humans ; Parkinson Disease/*genetics/metabolism/pathology ; Proteomics/*methods/trends ; Signal Transduction/*physiology ; },
abstract = {Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.},
}

Animals
*Databases, Genetic/trends
Gene Regulatory Networks/*physiology
Humans
Parkinson Disease/*genetics/metabolism/pathology
Proteomics/*methods/trends
Signal Transduction/*physiology

@article {pmid28002755,
year = {2017},
author = {Bora, E},
title = {Meta-analysis of social cognition in amyotrophic lateral sclerosis.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {88},
number = {},
pages = {1-7},
doi = {10.1016/j.cortex.2016.11.012},
pmid = {28002755},
issn = {1973-8102},
mesh = {Amyotrophic Lateral Sclerosis/*psychology ; Cognition/*physiology ; Emotions/*physiology ; Executive Function/physiology ; Facial Recognition/*physiology ; Humans ; *Social Perception ; Theory of Mind/*physiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is associated with executive dysfunction and behavioural impairment. Recent studies suggested that social cognitive deficits might also be a prominent feature of ALS. Current meta-analysis aimed to summarize available evidence for deficits in social cognition including theory of mind (ToM) and emotion recognition in ALS. In this meta-analysis of 15 studies, facial emotion recognition and ToM performances of 389 patients with ALS and 471 healthy controls were compared. ALS was associated with significant impairments with medium effect sizes in ToM (d = .65) and facial emotion recognition (d = .69). Among individual emotions recognition of disgust and surprise were particularly impaired. Deficits in perspective taking (d = .73) aspects of ToM (ToM-PT) was more pronounced in comparison to decoding (d = .28) aspects of ToM (ToM-decoding). The severity of social cognitive impairment was similar to level of executive dysfunction and there was a significant relationship between social cognition and executive dysfunction. Deficits in social cognition are part of the cognitive phenotype of ALS.},
}

Amyotrophic Lateral Sclerosis/*psychology
Cognition/*physiology
Emotions/*physiology
Executive Function/physiology
Facial Recognition/*physiology
Humans
*Social Perception
Theory of Mind/*physiology

@article {pmid27642606,
year = {2016},
author = {Bernabò, N and Ordinelli, A and Ramal Sanchez, M and Mattioli, M and Barboni, B},
title = {Networks Models of Actin Dynamics during Spermatozoa Postejaculatory Life: A Comparison among Human-Made and Text Mining-Based Models.},
journal = {BioMed research international},
volume = {2016},
number = {},
pages = {9795409},
pmid = {27642606},
issn = {2314-6141},
mesh = {Actins/*metabolism ; Ejaculation/physiology ; Fertilization/*physiology ; Humans ; Male ; Spermatozoa/*physiology ; },
abstract = {Here we realized a networks-based model representing the process of actin remodelling that occurs during the acquisition of fertilizing ability of human spermatozoa (HumanMade_ActinSpermNetwork, HM_ASN). Then, we compared it with the networks provided by two different text mining tools: Agilent Literature Search (ALS) and PESCADOR. As a reference, we used the data from the online repository Kyoto Encyclopaedia of Genes and Genomes (KEGG), referred to the actin dynamics in a more general biological context. We found that HM_ALS and the networks from KEGG data shared the same scale-free topology following the Barabasi-Albert model, thus suggesting that the information is spread within the network quickly and efficiently. On the contrary, the networks obtained by ALS and PESCADOR have a scale-free hierarchical architecture, which implies a different pattern of information transmission. Also, the hubs identified within the networks are different: HM_ALS and KEGG networks contain as hubs several molecules known to be involved in actin signalling; ALS was unable to find other hubs than "actin," whereas PESCADOR gave some nonspecific result. This seems to suggest that the human-made information retrieval in the case of a specific event, such as actin dynamics in human spermatozoa, could be a reliable strategy.},
}

Actins/*metabolism
Ejaculation/physiology
Fertilization/*physiology
Humans
Male
Spermatozoa/*physiology

@article {pmid27613758,
year = {2016},
author = {Goldstein, B and Speth, RC and Trivedi, M},
title = {Renin-angiotensin system gene expression and neurodegenerative diseases.},
journal = {Journal of the renin-angiotensin-aldosterone system : JRAAS},
volume = {17},
number = {3},
pages = {},
pmid = {27613758},
issn = {1752-8976},
mesh = {*Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Neurodegenerative Diseases/*genetics ; Renin-Angiotensin System/*genetics ; },
abstract = {HYPOTHESIS: Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases.

INTRODUCTION: Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease.

MATERIALS AND METHODS: A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis.

RESULTS: No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed.

CONCLUSIONS: To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases.},
}

*Gene Expression Regulation
Genome-Wide Association Study
Humans
Neurodegenerative Diseases/*genetics
Renin-Angiotensin System/*genetics

@article {pmid27515846,
year = {2016},
author = {de Vries, YA and Roest, AM and Franzen, M and Munafò, MR and Bastiaansen, JA},
title = {Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.},
journal = {Psychological medicine},
volume = {46},
number = {14},
pages = {2971-2979},
doi = {10.1017/S0033291716000805},
pmid = {27515846},
issn = {1469-8978},
support = {//British Heart Foundation/United Kingdom ; //Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; },
mesh = {*Bibliometrics ; *Depressive Disorder, Major/etiology/genetics ; Humans ; Publication Bias/*statistics & numerical data ; Serotonin Plasma Membrane Transport Proteins/*physiology ; *Stress, Psychological/complications ; },
abstract = {BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings.

METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.

RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.

CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.},
}

*Bibliometrics
*Depressive Disorder, Major/etiology/genetics
Humans
Publication Bias/*statistics & numerical data
Serotonin Plasma Membrane Transport Proteins/*physiology
*Stress, Psychological/complications

@article {pmid27094521,
year = {2016},
author = {Hu, X and Yang, Y and Su, J and Yao, C},
title = {Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation.},
journal = {Neurosciences (Riyadh, Saudi Arabia)},
volume = {21},
number = {2},
pages = {120-125},
pmid = {27094521},
issn = {1319-6138},
mesh = {Aged ; Amyotrophic Lateral Sclerosis/*blood ; Case-Control Studies ; Female ; Ferritins/*blood ; Humans ; Male ; Middle Aged ; },
abstract = {OBJECTIVE: To study the possible relationship between amyotrophic lateral sclerosis (ALS) patients and their susceptibility to serum ferritin level elevation.

METHODS: We searched the PubMed, Springer, Medline, and OVID databases for any-language original research articles relating to serum ferritin levels in ALS patients published between June 2005 and June 2015. The search term used with `amyotrophic lateral sclerosis`, `ferritins`, `ferritin`, `iron`, `iron stores, `iron status, `iron intake`, and `iron consumption`. The meta-analysis software RevMan 5.0 was used for the heterogeneity test, and to test for the overall effect.

RESULTS: Six case-control studies met our inclusion criteria including data from a total of 1813 participants. The mean difference of serum ferritin levels comparing ALS to healthy controls was 69.05 (95% confidence interval: 52.56-85.54; p<0.00001); heterogeneity: p=0.03; I2=50%. The findings indicate homology in the sensitivity analysis. Funnel plot assessment indicated publication bias.

CONCLUSION: Our results suggest that ALS is positively associated with susceptibility to the elevation of serum ferritin levels; however, further evidence is required to support this.},
}

Aged
Amyotrophic Lateral Sclerosis/*blood
Case-Control Studies
Female
Ferritins/*blood
Humans
Male
Middle Aged

@article {pmid26919175,
year = {2016},
author = {von Grabowiecki, Y and Abreu, P and Blanchard, O and Palamiuc, L and Benosman, S and Mériaux, S and Devignot, V and Gross, I and Mellitzer, G and Gonzalez de Aguilar, JL and Gaiddon, C},
title = {Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63.},
journal = {eLife},
volume = {5},
number = {},
pages = {},
pmid = {26919175},
issn = {2050-084X},
mesh = {Amyotrophic Lateral Sclerosis/*physiopathology ; Animals ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; Mice ; Muscle Proteins/*biosynthesis ; Muscles/pathology ; Transcription Factors/*biosynthesis ; Tripartite Motif Proteins ; Tumor Suppressor Protein p53/biosynthesis ; Tumor Suppressor Proteins/*biosynthesis ; Ubiquitin-Protein Ligases/*biosynthesis ; Up-Regulation ; },
abstract = {Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63.},
}

Amyotrophic Lateral Sclerosis/*physiopathology
Animals
Disease Models, Animal
Gene Expression Profiling
Humans
Mice
Muscle Proteins/*biosynthesis
Muscles/pathology
Transcription Factors/*biosynthesis
Tripartite Motif Proteins
Tumor Suppressor Protein p53/biosynthesis
Tumor Suppressor Proteins/*biosynthesis
Ubiquitin-Protein Ligases/*biosynthesis
Up-Regulation

@article {pmid26700797,
year = {2016},
author = {Lu, Y and Liu, W and Tan, K and Peng, J and Zhu, Y and Wang, X},
title = {Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {37},
number = {4},
pages = {525-532},
pmid = {26700797},
issn = {1590-3478},
mesh = {Alzheimer Disease/ethnology/*genetics ; Asian People/genetics ; Calcium Channels/*genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Membrane Glycoproteins/*genetics ; *Polymorphism, Single Nucleotide ; Risk ; White People/genetics ; },
abstract = {Recent studies investigating the association of Calcium homeostasis modulator 1 (CALHM1) p.P86L polymorphism (rs2986017) with Alzheimer's disease (AD) are controversial. Herein, we performed a meta-analysis to investigate the association between CALHM1 rs2986017 and AD risk. Literature searches of PubMed, Alzgene, and Embase were carried out up to 24 Nov 2015. The strength of the association between rs2986017 and AD was evaluated by odds ratio (OR) and 95 % confidence interval (CI). A total of 19 studies between 2008 and 2014 comprising 8777 AD cases and 8487 controls were included. Significant association of rs2986017 with AD was found in Caucasian population in allelic model (T vs. C: OR 1.13, 95 % CI 1.02-1.26, P = 0.022), and dominant model (TT + TC vs. CC: OR 1.15, 95 % CI 1.04-1.29, P = 0.018). No significant association was found in Asian population in any genetic model. Sensitivity analysis found that Dreses-Werringloer et al.'s might affect the overall result. The current meta-analysis suggested that CALHM1 rs2986017 might be associated with increased AD risk in Caucasian, but not Asian population.},
}

Alzheimer Disease/ethnology/*genetics
Asian People/genetics
Calcium Channels/*genetics
Genetic Association Studies
*Genetic Predisposition to Disease
Humans
Membrane Glycoproteins/*genetics
*Polymorphism, Single Nucleotide
Risk
White People/genetics

@article {pmid26362941,
year = {2015},
author = {Sheng, L and Ma, H and Zhong, J and Shang, H and Shi, H and Pan, P},
title = {Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies.},
journal = {Neurobiology of aging},
volume = {36},
number = {12},
pages = {3288-3299},
doi = {10.1016/j.neurobiolaging.2015.08.018},
pmid = {26362941},
issn = {1558-1497},
mesh = {Aging/pathology ; Amyotrophic Lateral Sclerosis/*pathology ; Anisotropy ; Atrophy ; Brain Mapping ; Gray Matter/*pathology ; Humans ; Motor Cortex/*pathology ; Regression Analysis ; },
abstract = {Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. Twenty studies, which reported 22 comparisons and were composed of 454 ALS patients and 426 healthy controls, were included in the meta-analyses. Regional GM atrophy in ALS was consistently found in the frontal, temporal, and somatosensory areas. Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker.},
}

Aging/pathology
Amyotrophic Lateral Sclerosis/*pathology
Anisotropy
Atrophy
Brain Mapping
Gray Matter/*pathology
Humans
Motor Cortex/*pathology
Regression Analysis

@article {pmid26255299,
year = {2015},
author = {Pan, L and Deng, X and Ding, D and Leng, H and Zhu, X and Wang, Z},
title = {Association between the Angiogenin (ANG) K17I variant and amyotrophic lateral sclerosis risk in Caucasian: a meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {36},
number = {12},
pages = {2163-2168},
pmid = {26255299},
issn = {1590-3478},
mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Case-Control Studies ; Female ; *Genetic Predisposition to Disease ; Humans ; Male ; Mutation/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Ribonuclease, Pancreatic/*genetics ; Risk ; White People ; },
abstract = {The study purpose is to perform a meta-analysis to help resolve the debate of whether the Angiogenin (ANG) K17I variant is associated with amyotrophic lateral sclerosis (ALS) risk in Caucasian. Three literature databases were searched for eligible studies published up to January 8, 2015: PubMed, Embase and Web of Science using the following search terms: amyotrophic lateral sclerosis or ALS and Angiogenin or ANG. Five eligible articles were identified, which reported 6 case-control studies and a total of 2326 cases and 3799 controls. The overall results suggested low frequencies of the K17I variant in Caucasian patients (10/2326, 0.43 %) and controls (6/3799, 0.16 %). There is no difference in the variant frequencies between patients with FALS or SALS (p = 0.069). Analysis of pooled odds ratios (ORs) and 95 % confidence intervals (CIs) revealed that the ANG K17I variant increases the risk for ALS (AT vs. AA: OR 2.65, 95 % CI 1.05-6.66, p = 0.038) and familial ALS (FALS) (AT vs. AA: OR 11.81, 95 % CI 2.11-66.15, p = 0.005) but not for sporadic ALS (SALS) (AT vs. AA: OR 1.63, 95 % CI 0.55-4.82, p = 0.378). The ANG K17I variant is rare in Caucasian patients and controls and increases the risk for ALS and FALS but not for SALS in Caucasian populations. Further well-designed studies with larger samples are needed to validate these results.},
}

Amyotrophic Lateral Sclerosis/*genetics
Case-Control Studies
Female
*Genetic Predisposition to Disease
Humans
Male
Mutation/*genetics
Polymorphism, Single Nucleotide/*genetics
Ribonuclease, Pancreatic/*genetics
Risk
White People

@article {pmid26001565,
year = {2015},
author = {Holtman, IR and Raj, DD and Miller, JA and Schaafsma, W and Yin, Z and Brouwer, N and Wes, PD and Möller, T and Orre, M and Kamphuis, W and Hol, EM and Boddeke, EW and Eggen, BJ},
title = {Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis.},
journal = {Acta neuropathologica communications},
volume = {3},
number = {},
pages = {31},
pmid = {26001565},
issn = {2051-5960},
mesh = {Aging/*genetics/immunology ; Alzheimer Disease/genetics ; Animals ; Humans ; Inflammation/*genetics ; Mice ; Microglia/*immunology ; NF-kappa B/genetics ; Neurodegenerative Diseases/*genetics/immunology ; Signal Transduction/*genetics ; Transcriptome/*genetics ; Up-Regulation ; },
abstract = {INTRODUCTION: Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).

RESULTS: A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified.

CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.},
}

Aging/*genetics/immunology
Alzheimer Disease/genetics
Animals
Humans
Inflammation/*genetics
Mice
Microglia/*immunology
NF-kappa B/genetics
Neurodegenerative Diseases/*genetics/immunology
Signal Transduction/*genetics
Transcriptome/*genetics
Up-Regulation

@article {pmid25881952,
year = {2015},
author = {Slade, A and Stanic, S},
title = {Managing excessive saliva with salivary gland irradiation in patients with amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {352},
number = {1-2},
pages = {34-36},
doi = {10.1016/j.jns.2015.02.008},
pmid = {25881952},
issn = {1878-5883},
mesh = {Adult ; Amyotrophic Lateral Sclerosis/complications/physiopathology/*radiotherapy ; Female ; Humans ; Male ; Middle Aged ; Parotid Gland/radiation effects ; Salivary Glands/*radiation effects ; Salivation/*radiation effects ; Sialorrhea/etiology/*radiotherapy ; Treatment Outcome ; },
abstract = {OBJECTIVE: A significant fraction of patients with amyotrophic lateral sclerosis (ALS) are unable to swallow saliva, which may result in the spillage of saliva outside of the oral cavity. Although anticholinergic agents and botulin toxin injections are considered the first line of treatment, they have not been effective for all patients. We performed a literature search on therapeutic salivary gland irradiation in patients with ALS.

METHODS: We searched the PubMed for English language publications up to December 2014 on therapeutic salivary gland irradiation in patients with ALS. The search was performed using the following key words: amyotrophic lateral sclerosis, excessive salivation, sialorrhea, and radiation therapy.

RESULTS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. The whole bilateral submandibular, and whole or partial bilateral parotid glands have been the target tissue for radiation therapy in most of the published studies. Various radiation therapy regimens have been utilized. The response to radiation therapy lasts for several months.

CONCLUSIONS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. Neurologists should consider this treatment option for select patients with ALS and excessive salivation.},
}

Adult
Amyotrophic Lateral Sclerosis/complications/physiopathology/*radiotherapy
Female
Humans
Male
Middle Aged
Parotid Gland/radiation effects
Salivary Glands/*radiation effects
Salivation/*radiation effects
Sialorrhea/etiology/*radiotherapy
Treatment Outcome

@article {pmid25806521,
year = {2015},
author = {Sun, X and Xu, D and Luo, F and Wei, Z and Wei, C and Xue, G},
title = {A cross-cultural perspective on the preference for potential effect: an individual participant data (IPD) meta-analysis approach.},
journal = {PloS one},
volume = {10},
number = {3},
pages = {e0124170},
pmid = {25806521},
issn = {1932-6203},
mesh = {China ; *Choice Behavior ; *Cross-Cultural Comparison ; Humans ; *Social Behavior ; United States ; },
abstract = {A recent paper [Tormala ZL, Jia JS, Norton MI (2012). The preference for potential. Journal of personality and social psychology, 103: 567-583] demonstrated that persons often prefer potential rather than achievement when evaluating others, because information regarding potential evokes greater interest and processing, resulting in more favorable evaluations. This research aimed to expand on this finding by asking two questions: (a) Is the preference for potential effect replicable in other cultures? (b) Is there any other mechanism that accounts for this preference for potential? To answer these two questions, we replicated Tormala et al.'s study in multiple cities (17 studies with 1,128 participants) in China using an individual participant data (IPD) meta-analysis approach to test our hypothesis. Our results showed that the preference for potential effect found in the US is also robust in China. Moreover, we also found a pro-youth bias behind the preference for potential effect. To be specific, persons prefer a potential-oriented applicant rather than an achievement-oriented applicant, partially because they believe that the former is younger than the latter.},
}

China
*Choice Behavior
*Cross-Cultural Comparison
Humans
*Social Behavior
United States

@article {pmid25654401,
year = {2015},
author = {Kivimäki, M and Singh-Manoux, A and Virtanen, M and Ferrie, JE and Batty, GD and Rugulies, R},
title = {IPD-Work consortium: pre-defined meta-analyses of individual-participant data strengthen evidence base for a link between psychosocial factors and health.},
journal = {Scandinavian journal of work, environment & health},
volume = {41},
number = {3},
pages = {312-321},
doi = {10.5271/sjweh.3485},
pmid = {25654401},
issn = {1795-990X},
support = {MR/K013351/1/MRC_/Medical Research Council/United Kingdom ; K013351/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Evidence-Based Practice ; *Health Status ; Humans ; *Psychology ; },
abstract = {Established in 2008 and comprising over 60 researchers, the IPD-Work (individual-participant data meta-analysis in working populations) consortium is a collaborative research project that uses pre-defined meta-analyses of individual-participant data from multiple cohort studies representing a range of countries. The aim of the consortium is to estimate reliably the associations of work-related psychosocial factors with chronic diseases, disability, and mortality. Our findings are highly cited by the occupational health, epidemiology, and clinical medicine research community. However, some of the IPD-Work's findings have also generated disagreement as they challenge the importance of job strain as a major target for coronary heart disease (CHD) prevention, this is reflected in the critical discussion paper by Choi et al (1). In this invited reply to Choi et al, we aim to (i) describe how IPD-Work seeks to advance research on associations between work-related psychosocial risk factors and health; (ii) demonstrate as unfounded Choi et al's assertion that IPD-Work has underestimated associations between job strain and health endpoints; these include the dichotomous measurement of job strain, potential underestimation of the population attributable risk (PAR) of job strain for CHD, and policy implications arising from the findings of the IPD-Work consortium; and (iii) outline general principles for designing evidence-based policy and prevention from good-quality evidence, including future directions for research on psychosocial factors at work and health. In addition, we highlight some problems with Choi et al's approach.},
}

*Evidence-Based Practice
*Health Status
Humans
*Psychology

@article {pmid25597926,
year = {2015},
author = {Jang, JS and Bae, JS},
title = {AWAJI criteria are not always superior to the previous criteria: A meta-analysis.},
journal = {Muscle & nerve},
volume = {51},
number = {6},
pages = {822-829},
doi = {10.1002/mus.24575},
pmid = {25597926},
issn = {1097-4598},
mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology ; Databases, Bibliographic/statistics & numerical data ; Demography ; Early Diagnosis ; Electromyography ; Humans ; ROC Curve ; },
abstract = {INTRODUCTION: Recently, some authors have claimed that the Awaji criteria (AC) are not always more sensitive than the revised El Escorial criteria (rEEC) in amyotrophic lateral sclerosis (ALS).

METHODS: A meta-analysis examined 2 prospective and 7 retrospective studies, which included 1,121 ALS patients, to compare AC and rEEC for early diagnosis of ALS.

RESULTS: AC led to an 11% greater likelihood of being classified into the categories "clinically definite" or "clinically probable", while if confined to the "clinically probable - laboratory supported (LS)" category, this effect was 40% higher with the rEEC (95% cnfidence interval, 3-82%; I2=98%). Specifically, AC downgraded 20% of the rEEC "clinically probable - LS" category to the AC "clinically possible".

CONCLUSIONS: Despite overall superiority of AC, this meta-analysis shows that it is not always more sensitive than rEEC. These results are related to the requirement for 2 upper motor neuron signs in the AC "clinically probable" category.},
}

Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology
Databases, Bibliographic/statistics & numerical data
Demography
Early Diagnosis
Electromyography
Humans
ROC Curve

@article {pmid25578179,
year = {2015},
author = {Chen, Y and Li, S and Su, L and Sheng, J and Lv, W and Chen, G and Xu, Z},
title = {Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis.},
journal = {Journal of neurology},
volume = {262},
number = {4},
pages = {814-822},
pmid = {25578179},
issn = {1432-1459},
mesh = {Alzheimer Disease/*genetics ; Amyotrophic Lateral Sclerosis/*genetics ; Frontotemporal Lobar Degeneration/*genetics ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics ; Parkinson Disease/*genetics ; Polymorphism, Single Nucleotide ; Progranulins ; },
abstract = {The purpose of this meta-analysis was to investigate the association between progranulin polymorphism rs5848 and risk of the neurodegenerative diseases frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Published literature from PubMed and other databases were retrieved, and 16 case-control studies were identified as eligible: 5 on FTLD (1,439 cases, 4,461 controls), 5 on AD (2,502 cases, 2,162 controls), 3 on PD (1,605 cases, 1,591 controls), and 3 on ALS (663 cases, 811 controls). The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. We found that rs5848 was associated with an increased risk of neurodegenerative diseases in the homozygous (TT vs. CC: OR, 1.24; 95% CI, 1.10-1.39; P < 0.001) and recessive models (TT vs. CC + CT: OR, 1.23; 95% CI, 1.10-1.37; P < 0.001). Stratified analyses showed associations of rs5848 with increased risk of AD and PD in the homozygous and recessive models. Our data indicate that rs5848 is associated with risk of AD and PD, suggesting important roles of progranulin in neurodegenerative processes.},
}

Alzheimer Disease/*genetics
Amyotrophic Lateral Sclerosis/*genetics
Frontotemporal Lobar Degeneration/*genetics
Humans
Intercellular Signaling Peptides and Proteins/*genetics
Parkinson Disease/*genetics
Polymorphism, Single Nucleotide
Progranulins

@article {pmid25449558,
year = {2015},
author = {Marchetti, M and Priftis, K},
title = {Brain-computer interfaces in amyotrophic lateral sclerosis: A metanalysis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {126},
number = {6},
pages = {1255-1263},
doi = {10.1016/j.clinph.2014.09.017},
pmid = {25449558},
issn = {1872-8952},
mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*physiopathology/*therapy ; *Brain-Computer Interfaces/trends ; *Communication Devices for People with Disabilities/trends ; Electroencephalography/methods/trends ; Humans ; },
abstract = {OBJECTIVE: Despite recent groundbreaking findings on the genetic causes of amyotrophic lateral sclerosis (ALS), and improvements on neuroimaging techniques for ALS diagnosis have been reported, the main clinical intervention in ALS remains palliative care. Brain-computer interfaces (BCIs) have been proposed as a channel of communication and control for ALS patients. The present metanalysis was performed to test the evidence of BCI effectiveness in ALS, and to investigate whether the promising aims emerged from the first studies have been reached.

METHODS: Studies on ALS patients tested with BCIs, until June 2013, were searched in PubMed and PsychInfo. The random-effect approach was used to compute the pooled effectiveness of BCI in ALS. A meta-regression was performed to test whether there was a BCI performance improvement as a function of time. Finally, BCI effectiveness for complete paralyzed ALS patients was tested. Twenty-seven studies were eligible for metanalysis.

RESULTS: The pooled classification accuracy (C.A.) of ALS patients with BCI was about 70%, but this estimation was affected by significant heterogeneity and inconsistency. C.A. did not significantly increase as a function of time. C.A. of completely paralyzed ALS patients with BCI did not differ from that obtained by chance.

CONCLUSIONS: After 15 years of studies, it is as yet not possible to reliably establish the effectiveness of BCIs.

SIGNIFICANCE: Methodological issues among the retrieved studies should be addressed and new well-powered studies should be conducted to confirm BCI effectiveness for ALS patients.},
}

Amyotrophic Lateral Sclerosis/diagnosis/*physiopathology/*therapy
*Brain-Computer Interfaces/trends
*Communication Devices for People with Disabilities/trends
Electroencephalography/methods/trends
Humans

@article {pmid25405377,
year = {2014},
author = {Capozzella, A and Sacco, C and Chighine, A and Loreti, B and Scala, B and Casale, T and Sinibaldi, F and Tomei, G and Giubilati, R and Tomei, F and Rosati, MV},
title = {Work related etiology of amyotrophic lateral sclerosis (ALS): a meta-analysis.},
journal = {Annali di igiene : medicina preventiva e di comunita},
volume = {26},
number = {5},
pages = {456-472},
doi = {10.7416/ai.2014.2005},
pmid = {25405377},
issn = {1120-9135},
mesh = {Amyotrophic Lateral Sclerosis/epidemiology/*etiology ; Electromagnetic Fields/adverse effects ; Female ; Humans ; Male ; Metals, Heavy/toxicity ; Occupational Diseases/epidemiology/*etiology/physiopathology ; Occupational Exposure/*adverse effects ; Pesticides/toxicity ; Research Design ; Risk Factors ; Sex Factors ; Solvents/toxicity ; },
abstract = {BACKGROUND: The aim of this meta-analysis was to evaluate the association between ALS and occupational exposure to physical (ELF-EMF) and chemicals (solvents, heavy metals and pesticides) agents.

METHODS: We considered articles published from 1980 up to April 2013; in total, 750 publications were evaluated. The studies had to satisfy the following criteria: 1) cohort or case-control studies; 2) the presence of individual exposures; 3) clinical diagnosis of sporadic ALS or sporadic ALS on the death certificate. We followed the evaluation of quality in two steps. The first step classified studies according to a rating system based on a mix of criteria developed by scientific organizations, especially developed for studies of risk factors for ALS. The ratings obtained range from I (highest) to V (lowest). The data on risk factors derived from studies with Armon ratings of I, II, and III can reach levels of evidence A (established risk factor), B (likely risk factor), or C (possible risk factor). The second step evaluated the exposure and a score from 1 to 4 was assigned to each item; an exposure with a score of 3 or 4 was considered sufficient. Different analyses were performed on ALS and exposure to metals, solvents, pesticides and electromagnetic fields. In our study the heterogeneity was assessed both by χ2-based Q-tests and through the index of inconsistency I² while the measure RR/OR and CI of 95% to estimate the relationship between ALS and the various considered risk factors was employed.

RESULTS: The association between exposure to pesticides and ALS as a whole is weak and not significant. With regard to the results of individual studies the following critical synthesis can be reported: 1) the selected studies showed a low level of association between ALS and electromagnetic fields; 2) as regards the solvents, the association with ALS in some studies is combined with a slightly increased risk, particularly in women, and in others a slight but significant linear association is observed; 3) for the metals, in some cases there was a stronger association in women than in men; for individual metals, there was an association especially with chromium and lead; 4) lastly, with regard to the products of agricultural pesticides in general, there was an association with ALS in men but not in women, with a dose-response relationship.

CONCLUSIONS: The lack of statistically significant association between occupational exposure and ALS is mainly due to the methodological diversity of the studies and the lack of prospective studies at the workplace.},
}

Amyotrophic Lateral Sclerosis/epidemiology/*etiology
Electromagnetic Fields/adverse effects
Female
Humans
Male
Metals, Heavy/toxicity
Occupational Diseases/epidemiology/*etiology/physiopathology
Occupational Exposure/*adverse effects
Pesticides/toxicity
Research Design
Risk Factors
Sex Factors
Solvents/toxicity

@article {pmid25238455,
year = {2014},
author = {Marcus, DK and O'Connell, D and Norris, AL and Sawaqdeh, A},
title = {Is the Dodo bird endangered in the 21st century? A meta-analysis of treatment comparison studies.},
journal = {Clinical psychology review},
volume = {34},
number = {7},
pages = {519-530},
doi = {10.1016/j.cpr.2014.08.001},
pmid = {25238455},
issn = {1873-7811},
mesh = {Adult ; Cognitive Behavioral Therapy/*statistics & numerical data ; *Data Interpretation, Statistical ; Female ; Humans ; Male ; Outcome Assessment, Health Care/*statistics & numerical data ; Randomized Controlled Trials as Topic/*statistics & numerical data ; },
abstract = {The Dodo bird hypothesis asserts that when bona fide treatments are compared they yield similar outcomes and this hypothesis is consistent with a common factors or contextual model of psychotherapy. Wampold et al. (1997), the most recent comprehensive meta-analysis to test the Dodo bird hypothesis, yielded consistent evidence of treatment equivalence. However, some of Wampold et al.'s analytic strategies, such as using multiple effect sizes from the same study and prioritizing long-term follow-up, may have obscured treatment differences. The current meta-analysis updated Wampold et al. by analyzing studies published in the subsequent 16 years (k=51). Separate effect sizes were calculated for primary outcomes versus secondary outcomes, at termination and follow-up. Contrary to the Dodo bird hypothesis, there was evidence of treatment differences for primary outcomes at termination. Furthermore, cognitive-behavioral treatments may be incrementally more effective than alternative treatments for primary outcomes. Consistent with the Dodo bird hypothesis, there was little evidence of treatment differences for the secondary outcomes at termination and follow-up. There are small, statistically significant differences between bona-fide treatments when the specific targets of those treatments are assessed, but not when secondary outcomes are assessed, providing mixed support for both specific factors and contextual models of psychotherapy.},
}

Adult
Cognitive Behavioral Therapy/*statistics & numerical data
*Data Interpretation, Statistical
Female
Humans
Male
Outcome Assessment, Health Care/*statistics & numerical data
Randomized Controlled Trials as Topic/*statistics & numerical data

@article {pmid24918518,
year = {2014},
author = {Govone, F and Vacca, A and Rubino, E and Gai, A and Boschi, S and Gentile, S and Orsi, L and Pinessi, L and Rainero, I},
title = {Lack of association between APOE gene polymorphisms and amyotrophic lateral sclerosis: a comprehensive meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {15},
number = {7-8},
pages = {551-556},
doi = {10.3109/21678421.2014.918149},
pmid = {24918518},
issn = {2167-9223},
mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Apolipoproteins E/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Odds Ratio ; Polymorphism, Single Nucleotide/*genetics ; },
abstract = {Several studies have evaluated the association between APOE gene polymorphisms and the risk for amyotrophic lateral sclerosis (ALS), with inconclusive results. The aim of our study was to further define the risk associated with carriage of the APOE alleles and development and clinical characteristics of ALS. We performed a comprehensive meta-analysis of all existing studies investigating the association between the APOE gene and ALS published up to September 2013, comprising a total of 4249 ALS patients and 10,397 controls. Pooled odds ratios (OR) were estimated using the random effect (RE) model. Results showed that the carriage of different APOE alleles had no effect on disease risk. In particular, the ϵ4 allele was not associated with a significantly increased disease risk (ϵ4 carriers vs. non-ϵ4 carriers: RE OR 1.18; 95% CI 0.91-1.53). In conclusion, our study suggests that the APOE gene does not have a significant effect in ALS aetiopathogenesis.},
}

Amyotrophic Lateral Sclerosis/*genetics
Apolipoproteins E/*genetics
Female
Gene Frequency
Genetic Predisposition to Disease/*genetics
Genotype
Humans
Male
Odds Ratio
Polymorphism, Single Nucleotide/*genetics

@article {pmid24699859,
year = {2014},
author = {Abraham, A and Drory, VE},
title = {Influence of serum uric acid levels on prognosis and survival in amyotrophic lateral sclerosis: a meta-analysis.},
journal = {Journal of neurology},
volume = {261},
number = {6},
pages = {1133-1138},
pmid = {24699859},
issn = {1432-1459},
mesh = {Amyotrophic Lateral Sclerosis/*blood/*mortality ; Female ; Humans ; Male ; Prognosis ; PubMed/statistics & numerical data ; Sex Factors ; Uric Acid/*blood ; },
abstract = {Uric acid (UA) is considered to be one of the most important antioxidants in the blood. While high UA levels are found in many disease states, low UA levels are reported in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). Various studies showed consistently that ALS patients have lower serum UA levels than healthy individuals, more prominently in cases with bulbar onset and longer disease duration. A systematic search of PubMed was conducted to retrieve published studies on UA levels in ALS patients. A meta-analysis was performed on published studies comparing UA levels between ALS patients and controls. This meta-analysis revealed highly statistically significant (p < 0.0001) lower UA levels and a very large size effect in 311 ALS patients compared to 515 controls as a group, as well as calculated for men and women separately. Many studies indicate that patients with neurodegenerative diseases, including ALS, have low UA levels. Our meta-analysis strengthens these findings in ALS patients, demonstrating highly statistically significant (p < 0.0001) lower UA levels in patients compared to controls, with very large total size effect, more prominent in men.},
}

Amyotrophic Lateral Sclerosis/*blood/*mortality
Female
Humans
Male
Prognosis
PubMed/statistics & numerical data
Sex Factors
Uric Acid/*blood

@article {pmid24672220,
year = {2014},
author = {Liu, J and Zhang, HX},
title = {Polymorphism in the 11q24.1 genomic region is associated with myopia: a comprehensive genetic study in Chinese and Japanese populations.},
journal = {Molecular vision},
volume = {20},
number = {},
pages = {352-358},
pmid = {24672220},
issn = {1090-0535},
mesh = {Asian People/*genetics ; China ; Chromosomes, Human, Pair 11/*genetics ; Female ; Genetic Association Studies ; Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Genome, Human/*genetics ; Humans ; Japan ; Male ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; },
abstract = {PURPOSE: To evaluate the association of polymorphisms in the 11q24.1 genomic region and the CTNND2 gene with myopia.

METHODS: We conducted a comprehensive meta-analysis included 6,954 cases and 9,346 controls. Odds ratios (ORs) were calculated using Carlin's method. Publication bias was assessed using Egger et al.'s approach. Sensitivity, heterogeneity, and trim and fill analyses were also conducted.

RESULTS: For the 11q24.1 genomic region, the rs11218544 polymorphism showed significant association with myopia [OR and 95% confidence interval (CI): 1.167 (1.032-1.319), p=0.013], while rs577948 showed no association with the disease [OR and 95%CI: 0.988 (0.727-1.342), p=0.936]. For the CTNND2 gene, neither rs6885224 nor rs12716080 was significantly associated with myopia {rs6885224: [OR and 95%CI: 1.051 (0.795-1.391), p=0.725], rs12716080: [OR and 95%CI: 1.173 (0.990-1.390), p=0.065]}.


CONCLUSIONS: Our study indicated that the 11q24.1 genomic region, and particularly the rs11218544 polymorphism, has a genetic association with the development of myopia.},
}

Asian People/*genetics
China
Chromosomes, Human, Pair 11/*genetics
Female
Genetic Association Studies
Genetic Heterogeneity
*Genetic Predisposition to Disease
Genome, Human/*genetics
Humans
Japan
Male
Myopia/*genetics
Polymorphism, Single Nucleotide/*genetics
Publication Bias

@article {pmid24630593,
year = {2014},
author = {Wang, XB and Cui, NH and Gao, JJ and Qiu, XP and Zheng, F},
title = {SMN1 duplications contribute to sporadic amyotrophic lateral sclerosis susceptibility: evidence from a meta-analysis.},
journal = {Journal of the neurological sciences},
volume = {340},
number = {1-2},
pages = {63-68},
doi = {10.1016/j.jns.2014.02.026},
pmid = {24630593},
issn = {1878-5883},
mesh = {Amyotrophic Lateral Sclerosis/*genetics ; DNA Copy Number Variations ; Databases, Factual/statistics & numerical data ; *Genetic Predisposition to Disease ; Humans ; Survival of Motor Neuron 1 Protein/*genetics ; },
abstract = {OBJECTIVE: To investigate the association between SMN1 and SMN2 copy number variations (CNVs) and sporadic amyotrophic lateral sclerosis (SALS) by a meta-analysis.

METHODS: Through searching PubMed and EMBASE database (or manual searching) up to November 2013 using the following keywords: "survival motor neuron gene", "SMN", and "amyotrophic lateral sclerosis", "ALS" or "motor neuron disease". Nine studies were identified as eligible for this meta-analysis. The association between SMN genes and the SALS risk was investigated based on SMN1 and SMN2 CNVs. The heterogeneity across the studies was tested, as was publication bias.

RESULTS: The analysis showed significant association for SMN1 duplications in SALS risk: the risk estimates were OR=1.76, 95%CI=1.33-2.32, p<0.0001 (still significant when the p value was Bonferroni adjusted to 0.01). However, there was no significant association between SMN1 deletions and SALS risk after Bonferroni correction (OR=1.78, 95%CI=1.02-3.11, p=0.04). In addition, SMN2 copy number statuses were not associated with SALS in our pooled study. No evidence of publication bias was observed.

CONCLUSION: Our meta-analysis suggested that SMN1 duplications are a genetic risk factor in SALS, while there was no modulator effect of the SMN2 gene. In addition, it was possible that SMN1 deletions in predisposition to SALS vary across different countries. More studies were required to warrant the findings of this study.},
}

Amyotrophic Lateral Sclerosis/*genetics
DNA Copy Number Variations
Databases, Factual/statistics & numerical data
*Genetic Predisposition to Disease
Humans
Survival of Motor Neuron 1 Protein/*genetics

@article {pmid24458030,
year = {2014},
author = {Catalá-López, F and Suárez-Pinilla, M and Suárez-Pinilla, P and Valderas, JM and Gómez-Beneyto, M and Martinez, S and Balanzá-Martínez, V and Climent, J and Valencia, A and McGrath, J and Crespo-Facorro, B and Sanchez-Moreno, J and Vieta, E and Tabarés-Seisdedos, R},
title = {Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies.},
journal = {Psychotherapy and psychosomatics},
volume = {83},
number = {2},
pages = {89-105},
doi = {10.1159/000356498},
pmid = {24458030},
issn = {1423-0348},
support = {NIHR/CS/010/024/DH_/Department of Health/United Kingdom ; },
mesh = {Alzheimer Disease/epidemiology ; Amyotrophic Lateral Sclerosis/epidemiology ; Central Nervous System Diseases/*epidemiology ; Child Development Disorders, Pervasive/epidemiology ; Comorbidity ; Down Syndrome/epidemiology ; Humans ; Huntington Disease/epidemiology ; Incidence ; Multiple Sclerosis/epidemiology ; Neoplasms/*epidemiology ; Observational Studies as Topic ; Parkinson Disease/epidemiology ; Schizophrenia/epidemiology ; },
abstract = {BACKGROUND: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ).

METHOD: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively.

RESULTS: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ).

CONCLUSION: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.},
}

Alzheimer Disease/epidemiology
Amyotrophic Lateral Sclerosis/epidemiology
Central Nervous System Diseases/*epidemiology
Child Development Disorders, Pervasive/epidemiology
Comorbidity
Down Syndrome/epidemiology
Humans
Huntington Disease/epidemiology
Incidence
Multiple Sclerosis/epidemiology
Neoplasms/*epidemiology
Observational Studies as Topic
Parkinson Disease/epidemiology
Schizophrenia/epidemiology

@article {pmid24238842,
year = {2014},
author = {Vaa, T},
title = {ADHD and relative risk of accidents in road traffic: a meta-analysis.},
journal = {Accident; analysis and prevention},
volume = {62},
number = {},
pages = {415-425},
doi = {10.1016/j.aap.2013.10.003},
pmid = {24238842},
issn = {1879-2057},
mesh = {Accidents, Traffic/*statistics & numerical data ; Attention Deficit Disorder with Hyperactivity/*epidemiology ; Attention Deficit and Disruptive Behavior Disorders/epidemiology ; Automobile Driving/*statistics & numerical data ; Comorbidity ; Conduct Disorder/epidemiology ; Female ; Humans ; Male ; Risk ; },
abstract = {The present meta-analysis is based on 16 studies comprising 32 results. These studies provide sufficient data to estimate relative accident risks of drivers with ADHD. The overall estimate of relative risk for drivers with ADHD is 1.36 (95% CI: 1.18; 1.57) without control for exposure, 1.29 (1.12; 1.49) when correcting for publication bias, and 1.23 (1.04; 1.46) when controlling for exposure. A relative risk (RR) of 1.23 is exactly the same as found for drivers with cardiovascular diseases. The long-lasting assertion that "ADHD-drivers have an almost fourfold risk of accident compared to non-ADHD-drivers", which originated from Barkley et al.'s study of 1993, is rebutted. That estimate was associated with comorbid Oppositional Defiant Disorder (ODD) and/or Conduct Disorder (CD), not with ADHD, but the assertion has incorrectly been maintained for two decades. The present study provides some support for the hypothesis that the relative accident risk of ADHD-drivers with comorbid ODD, CD and/or other conduct problems, is higher than that of ADHD-drivers without these comorbidities. The estimated RRs were 1.86 (1.27; 2.75) in a sample of ADHD-drivers in which a majority had comorbid ODD and/or CD compared to 1.31 (0.96; 1.81) in a sample of ADHD-drivers with no comorbidity. Given that ADHD-drivers most often seem to drive more than controls, and the fact that a majority of the present studies lack information about exposure, it seems more probable that the true RR is lower rather than higher than 1.23. Also the assertion that ADHD-drivers violate traffic laws more often than other drivers should be modified: ADHD-drivers do have more speeding violations, but no more drunk or reckless driving citations than drivers without ADHD. All accident studies included in the meta-analysis fail to acknowledge the distinction between deliberate violations and driving errors. The former are known to be associated with accidents, the latter are not. A hypothesis that ADHD-drivers speed more frequently than controls because it stimulates attention and reaction time is suggested.},
}

Accidents, Traffic/*statistics & numerical data
Attention Deficit Disorder with Hyperactivity/*epidemiology
Attention Deficit and Disruptive Behavior Disorders/epidemiology
Automobile Driving/*statistics & numerical data
Comorbidity
Conduct Disorder/epidemiology
Female
Humans
Male
Risk

@article {pmid24044580,
year = {2013},
author = {Huang, M and Wang, L and Ma, H and Wang, J and Xiang, M},
title = {Lack of an association between interleukin-6 -174G/C polymorphism and circulating interleukin-6 levels in normal population: a meta-analysis.},
journal = {DNA and cell biology},
volume = {32},
number = {11},
pages = {654-664},
doi = {10.1089/dna.2013.2148},
pmid = {24044580},
issn = {1557-7430},
mesh = {Coronary Disease/genetics ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Interleukin-6/*blood/*genetics ; *Polymorphism, Single Nucleotide ; Reference Values ; },
abstract = {Interleukin-6 (IL-6) signaling may play a causal role in the development of coronary heart disease. However, the relationship between IL-6 genotypes and plasma levels of IL-6 appears to be complex. To help clarify the inconsistent findings, we conducted a meta-analysis of the published genetic association studies of the -174 G/C polymorphisms in the IL-6 gene and the circulating IL-6 levels in a normal population. In this meta-analysis, no significant association of IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population was observed. However, when compared among GG, GC, and CC genotypes, heterogeneity existed among the studies. Sensitivity analysis revealed that, the independent study by Shen et al. influenced the heterogeneity in the homozygous and heterozygous comparison. Although Shen et al.'s study was excluded, no significant association was observed between IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population [homozygous comparison (GG vs. CC): the pooled standard mean difference (SMD) was -0.01, 95% confidence interval (CI): -0.1-0.08; heterozygous comparison (GC vs. GG or CC): the pooled SMD (GG vs. GC) was -0.05, 95%CI: -0.11-0.01, and the pooled SMD (CC vs. GC) was 0.03, 95%CI: -0.03-0.1]. Under the dominant model, the pooled SMD was -0.05, 95%CI: -0.11-0.01). The meta-analysis provides evidence that the -174G/C polymorphism in the IL-6 gene is not significantly associated with circulating IL-6 levels in a normal population.},
}

Coronary Disease/genetics
Genetic Predisposition to Disease
Heterozygote
Humans
Interleukin-6/*blood/*genetics
*Polymorphism, Single Nucleotide
Reference Values

@article {pmid23856242,
year = {2013},
author = {Bowen, RC and Wang, Y and Balbuena, L and Houmphan, A and Baetz, M},
title = {The relationship between mood instability and depression: implications for studying and treating depression.},
journal = {Medical hypotheses},
volume = {81},
number = {3},
pages = {459-462},
doi = {10.1016/j.mehy.2013.06.010},
pmid = {23856242},
issn = {1532-2777},
mesh = {Depression/complications/*diagnosis/*physiopathology ; Factor Analysis, Statistical ; Humans ; Mood Disorders/complications/*physiopathology ; Surveys and Questionnaires ; United Kingdom ; },
abstract = {BACKGROUND: Most individuals with depressed mood report mood fluctuations (Mood Instability) within hours or days. This is not recognized in diagnostic criteria or standard rating scales for depression.

HYPOTHESIS: That mood instability is a distinct component of the development of depression that has been omitted from criteria for depression because of reliance on retrospective recall and structured interviews. The inclusion of Mood Instability would enhance research into causes and treatment of depression.

STUDIES: We examined three datasets that used retrospective and prospective measures of depressed symptom ratings and mood instability to determine the relationship between the two. Study 1 used data from the 1991 UK Health and Lifestyle Surveys (HALS). Studies 2 and 3 used clinical samples. The scales used to assess mood instability were the mood instability factor from the Eysenck Personality Inventory Neuroticism Scale, the Affective Lability Scale (ALS), and the Visual Analogue Depression Scale (VAS). The depression scales (depressive symptoms) were the General Health Questionnaire (GHQ) depression factor, the Beck Depression Inventory IA (BDI) and the mean from the Visual Analogue Depression Scale (VAS). We used partial correlation analysis to assess the association between mood instability and depression and exploratory factor analysis to determine the factor structure of items pooled from the mood instability and depression scales from studies 1 and 2.

RESULTS: Mood Instability was found to be moderately associated with depressive symptoms. The Pearson's r-values ranged from 0.49 to 0.57. The correlation was lower when recalling mood in the past. The factor analytic solution supported the hypothesis that MI and depressive symptoms are related but distinct constructs.

CONCLUSIONS: Reliance exclusively on the retrospective assessment of depressive symptoms has occluded the widespread occurrence of mood instability. Including Mood Instability in diagnostic and assessment criteria would enhance causal and treatment research in depression.},
}

Depression/complications/*diagnosis/*physiopathology
Factor Analysis, Statistical
Humans
Mood Disorders/complications/*physiopathology
Surveys and Questionnaires
United Kingdom

@article {pmid23286751,
year = {2013},
author = {Saris, CG and Groen, EJ and Koekkoek, JA and Veldink, JH and van den Berg, LH},
title = {Meta-analysis of gene expression profiling in amyotrophic lateral sclerosis: a comparison between transgenic mouse models and human patients.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {14},
number = {3},
pages = {177-189},
doi = {10.3109/21678421.2012.729842},
pmid = {23286751},
issn = {2167-9223},
mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*genetics ; Animals ; *Disease Models, Animal ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Humans ; Mice ; Mice, Transgenic ; },
abstract = {The exact pathogenic cascade leading to motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is unknown. Gene expression profiles of ALS-affected spinal cord and motor neurons have been well established in mice and man. We provide a meta-analysis of the reported significant gene lists of gene expression studies in ALS, and compare results between mouse models and human post mortem tissue. In total, 12 articles met inclusion criteria. Twenty-nine genes were found to be differentially expressed at least twice in studies using human post mortem tissue, enriched for the functions 'immune response', 'apoptosis' and 'protein metabolism'. In mouse studies, 86 genes were reported at least two times and were enriched for 'immune response', 'lysosome', 'metal ion binding' and 'mitochondrion'. Next, all differentially expressed genes from the mouse studies were translated to human homologous genes. Seventy-four differentially expressed genes in mouse tissue were also found to be differentially expressed in human tissue. In conclusion, evidence was found for shared dysfunction in protein turnover in the ubiquitin-proteasome system. Differential expression of Cathepsin B and D, GFAP and SERPINA3 was repeatedly found to be significant in both the mouse model and ALS patients.},
}

Amyotrophic Lateral Sclerosis/diagnosis/*genetics
Animals
*Disease Models, Animal
Gene Expression Profiling/*methods
*Gene Expression Regulation
Humans
Mice
Mice, Transgenic

@article {pmid23267027,
year = {2016},
author = {Combescure, C and Courvoisier, DS and Haller, G and Perneger, TV},
title = {Meta-analysis of two-arm studies: Modeling the intervention effect from survival probabilities.},
journal = {Statistical methods in medical research},
volume = {25},
number = {2},
pages = {857-871},
doi = {10.1177/0962280212469716},
pmid = {23267027},
issn = {1477-0334},
mesh = {Breast Neoplasms/diagnosis/mortality ; Disease-Free Survival ; Early Detection of Cancer ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy/surgery ; Neoplasm Recurrence, Local/diagnosis/mortality ; *Proportional Hazards Models ; Time Factors ; },
abstract = {Pooling the hazard ratios is not always feasible in meta-analyses of two-arm survival studies, because the measure of the intervention effect is not systematically reported. An alternative approach proposed by Moodie et al. is to use the survival probabilities of the included studies, all collected at a single point in time: the intervention effect is then summarised as the pooled ratio of the logarithm of survival probabilities (which is an estimator of the hazard ratios when hazards are proportional). In this article, we propose a generalization of this method. By using survival probabilities at several points in time, this generalization allows a flexible modeling of the intervention over time. The method is applicable to partially proportional hazards models, with the advantage of not requiring the specification of the baseline survival. As in Moodie et al.'s method, the study-level factors modifying the survival functions can be ignored as long as they do not modify the intervention effect. The procedures of estimation are presented for fixed and random effects models. Two illustrative examples are presented.},
}

Breast Neoplasms/diagnosis/mortality
Disease-Free Survival
Early Detection of Cancer
Female
Humans
Leukemia, Myeloid, Acute/drug therapy/surgery
Neoplasm Recurrence, Local/diagnosis/mortality
*Proportional Hazards Models
Time Factors

@article {pmid23189129,
year = {2012},
author = {Zhou, H and Chen, G and Chen, C and Yu, Y and Xu, Z},
title = {Association between extremely low-frequency electromagnetic fields occupations and amyotrophic lateral sclerosis: a meta-analysis.},
journal = {PloS one},
volume = {7},
number = {11},
pages = {e48354},
pmid = {23189129},
issn = {1932-6203},
mesh = {Amyotrophic Lateral Sclerosis/epidemiology/*etiology ; Electromagnetic Fields/*adverse effects ; Humans ; Occupational Exposure ; Odds Ratio ; Publication Bias ; },
abstract = {OBJECTIVES: To estimate the relationship between exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and the risk of amyotrophic lateral sclerosis (ALS) by a meta-analysis.

METHODS: Through searching PubMed databases (or manual searching) up to April 2012 using the following keywords: "occupational exposure", "electromagnetic fields" and "amyotrophic lateral sclerosis" or "motor neuron disease", seventeen studies were identified as eligible for this meta-analysis. The associations between ELF-EMF exposure and the ALS risk were estimated based on study design (case-control or cohort study), and ELF-EMF exposure level assessment (job title or job-exposure matrix). The heterogeneity across the studies was tested, as was publication bias.

RESULTS: Occupational exposure to ELF-EMF was significantly associated with increased risk of ALS in pooled studies (RR = 1.29, 95%CI = 1.02-1.62), and case-control studies (OR = 1.39, 95%CI = 1.05-1.84), but not cohort studies (RR = 1.16, 95% CI = 0.80-1.69). In sub-analyses, similar significant associations were found when the exposure level was defined by the job title, but not the job-exposure matrix. In addition, significant associations between occupational exposure to ELF-EMF and increased risk of ALS were found in studies of subjects who were clinically diagnosed but not those based on the death certificate. Moderate heterogeneity was observed in all analyses.

CONCLUSIONS: Our data suggest a slight but significant ALS risk increase among those with job titles related to relatively high levels of ELF-EMF exposure. Since the magnitude of estimated RR was relatively small, we cannot deny the possibility of potential biases at work. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may be responsible for the observed associations with ALS.},
}

Amyotrophic Lateral Sclerosis/epidemiology/*etiology
Electromagnetic Fields/*adverse effects
Humans
Occupational Exposure
Odds Ratio
Publication Bias

@article {pmid23063643,
year = {2013},
author = {van Rheenen, W and Diekstra, FP and van Doormaal, PT and Seelen, M and Kenna, K and McLaughlin, R and Shatunov, A and Czell, D and van Es, MA and van Vught, PW and van Damme, P and Smith, BN and Waibel, S and Schelhaas, HJ and van der Kooi, AJ and de Visser, M and Weber, M and Robberecht, W and Hardiman, O and Shaw, PJ and Shaw, CE and Morrison, KE and Al-Chalabi, A and Andersen, PM and Ludolph, AC and Veldink, JH and van den Berg, LH},
title = {H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis.},
journal = {Neurobiology of aging},
volume = {34},
number = {5},
pages = {1517.e5-7},
doi = {10.1016/j.neurobiolaging.2012.07.020},
pmid = {23063643},
issn = {1558-1497},
support = {089701/WT_/Wellcome Trust/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*epidemiology/*genetics ; Europe/epidemiology ; Female ; Genetic Markers/*genetics ; Genetic Predisposition to Disease/*epidemiology/*genetics ; Hemochromatosis Protein ; Histocompatibility Antigens Class I/*genetics ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Polymorphism, Single Nucleotide/*genetics ; Prevalence ; Risk Factors ; },
abstract = {The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.},
}

Adult
Aged
Amyotrophic Lateral Sclerosis/*epidemiology/*genetics
Europe/epidemiology
Female
Genetic Markers/*genetics
Genetic Predisposition to Disease/*epidemiology/*genetics
Hemochromatosis Protein
Histocompatibility Antigens Class I/*genetics
Humans
Male
Membrane Proteins/*genetics
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Prevalence
Risk Factors

@article {pmid22819005,
year = {2012},
author = {Malek, AM and Barchowsky, A and Bowser, R and Youk, A and Talbott, EO},
title = {Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: a meta-analysis of epidemiological studies: pesticide exposure as a risk factor for ALS.},
journal = {Environmental research},
volume = {117},
number = {},
pages = {112-119},
doi = {10.1016/j.envres.2012.06.007},
pmid = {22819005},
issn = {1096-0953},
mesh = {*Agriculture ; Amyotrophic Lateral Sclerosis/*chemically induced/*epidemiology ; Humans ; Male ; Models, Statistical ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pesticides/*toxicity ; Risk Factors ; },
abstract = {BACKGROUND: Exposure to pesticides and agricultural chemicals has been linked to amyotrophic lateral sclerosis (ALS) although findings have been inconsistent. A meta-analysis of studies published through May, 2011 was conducted to investigate the association of pesticide exposure and risk of ALS.

METHODS: Six peer-reviewed studies that met criteria were included in a meta-analysis of men involving 1,517 ALS deaths from one retrospective cohort study and 589 ALS or motor neuron disease cases from five case-control studies. A random effects model was used to calculate sex-specific pooled odds ratios (ORs).

RESULTS: Evidence was found for an association of exposure to pesticides and risk of ALS in male cases compared to controls (OR=1.88, 95% CI: 1.36-2.61), although the chemical or class of pesticide was not specified by the majority of studies.

CONCLUSION: This meta-analysis supports the relationship of exposure to pesticides and development of ALS among male cases compared to controls. The weight of evidence links pesticide exposure to ALS; however, additional prospective studies with a target exposure group are necessary to better elucidate the relationship. Future research should focus on more accurate exposure assessment and the use of job exposure matrices.},
}

*Agriculture
Amyotrophic Lateral Sclerosis/*chemically induced/*epidemiology
Humans
Male
Models, Statistical
Occupational Exposure/*adverse effects
Odds Ratio
Pesticides/*toxicity
Risk Factors

@article {pmid22059178,
year = {2011},
author = {McKim, DA and Road, J and Avendano, M and Abdool, S and Cote, F and Duguid, N and Fraser, J and Maltais, F and Morrison, DL and O'Connell, C and Petrof, BJ and Rimmer, K and Skomro, R and , },
title = {Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline.},
journal = {Canadian respiratory journal},
volume = {18},
number = {4},
pages = {197-215},
pmid = {22059178},
issn = {1916-7245},
mesh = {Adult ; *Airway Management/instrumentation/methods/standards ; Clinical Trials as Topic ; *Home Care Services ; Humans ; *Monitoring, Physiologic/methods/standards ; Musculoskeletal Diseases/complications ; Nervous System Diseases/complications ; Obesity Hypoventilation Syndrome/complications ; Patient Discharge/standards ; Pulmonary Disease, Chronic Obstructive/complications ; *Respiration, Artificial/instrumentation/methods/standards ; Respiratory Function Tests ; *Respiratory Insufficiency/diagnosis/etiology/physiopathology/therapy ; Risk Assessment ; },
abstract = {Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.},
}

Adult
*Airway Management/instrumentation/methods/standards
Clinical Trials as Topic
*Home Care Services
Humans
*Monitoring, Physiologic/methods/standards
Musculoskeletal Diseases/complications
Nervous System Diseases/complications
Obesity Hypoventilation Syndrome/complications
Patient Discharge/standards
Pulmonary Disease, Chronic Obstructive/complications
*Respiration, Artificial/instrumentation/methods/standards
Respiratory Function Tests
*Respiratory Insufficiency/diagnosis/etiology/physiopathology/therapy
Risk Assessment

@article {pmid21914052,
year = {2012},
author = {, and Andersen, PM and Abrahams, S and Borasio, GD and de Carvalho, M and Chio, A and Van Damme, P and Hardiman, O and Kollewe, K and Morrison, KE and Petri, S and Pradat, PF and Silani, V and Tomik, B and Wasner, M and Weber, M},
title = {EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force.},
journal = {European journal of neurology},
volume = {19},
number = {3},
pages = {360-375},
doi = {10.1111/j.1468-1331.2011.03501.x},
pmid = {21914052},
issn = {1468-1331},
mesh = {Advisory Committees ; Amyotrophic Lateral Sclerosis/*diagnosis/*therapy ; Evidence-Based Medicine ; Humans ; },
abstract = {BACKGROUND: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak.

OBJECTIVES: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel.

METHODS: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus.

RECOMMENDATIONS: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.},
}

Advisory Committees
Amyotrophic Lateral Sclerosis/*diagnosis/*therapy
Evidence-Based Medicine
Humans

@article {pmid21644273,
year = {2011},
author = {Hunyadi-Anticević, S and Colak, Z and Funtak, IL and Lukić, A and Filipović-Grcić, B and Tomljanović, B and Kniewald, H and Protić, A and Pandak, T and Poljaković, Z and Canadija, M and , },
title = {[European Resuscitation Council guidelines for resuscitation 2010].},
journal = {Lijecnicki vjesnik},
volume = {133},
number = {1-2},
pages = {1-14},
pmid = {21644273},
issn = {0024-3477},
mesh = {Acute Coronary Syndrome/therapy ; Adult ; Cardiopulmonary Resuscitation/*methods/standards ; Child ; *Emergency Medical Services ; Humans ; Infant, Newborn ; Myocardial Infarction/therapy ; },
abstract = {All rescuers trained or not, should provide chest compressions to victims of cardiac arrest. The aim should be to push to a depth of at least 5 cm at a rate of at least 100 compressions per minute, to allow full chest recoil, and to minimise interruptions in chest compressions. Trained rescuers should also provide ventilations with a compression-ventilation ratio of 30:2. ELECTRICAL THERAPIES: Much greater emphasis on minimising the duration of the pre-shock and post-shock pauses; the continuation of compressions during charging of the defibrillator is recommended. Further development of AED programmes is encouraged. ADULT ADVANCED LIFE SUPPORT: Increased emphasis on high-quality chest compressions throughout any ALS intervention paused briefly only to enable specific interventions. Removal of the recommendation for a pre-specified period of cardiopulmonary resuscitation before out-of-hospital defibrillation following cardiac arrest unwitnessed by the EMS. The role of precordial thump is de-emphasized. Delivery of drugs via a tracheal tube is no longer recommended, drugs should be given by the intraosseous (IO) route. Atropine is no longer recommended for routine use in asystole or pulseless electrical activity. Reduced emphasis on early tracheal intubation unless achieved by highly skilled individuals with minimal interruptions in chest compressions. Increased emphasis on the use of capnography. Recognition of potential harm caused by hyperoxaemia. Revision of the recommendation of glucose control. Use of therapeutic hypothermia to include comatose survivors of cardiac arrest associated initially with shockable rhythms, as well as non-shockable rhythms, with a lower level of evidence acknowledged for the latter. INITIAL MANAGEMENT OF ACUTE CORONARY SYNDROMES: The term non-ST-elevation myocardial infarction-acute coronary syndrome (non-STEMI-ACS) has been introduced for both NSTEMI and unstable angina pectoris. Primary PCI (PPCI) is the preferred reperfusion strategy provided it is performed in a timely manner by an experienced team. Non-steroidal anti-inflammatory drugs should be avoided, as well as routine use of intravenous beta-blockers; oxygen is to be given only to those patients with hypoxaemia, breathlessness or pulmonary congestion. PAEDIATRIC LIFE SUPPORT: The decision to begin resuscitation must be taken in less than 10 seconds. Lay rescuers should be taught to use a ratio of 30 compressions to 2 ventilations, rescuers with a duty to respond should learn and use a 15:2 ratio; however, they can use the 30:2 compression-ventilation ratio if they are alone. Ventilation remains a very important component of resuscitation in asphyxial arrest. The emphasis is on achieving quality compressions with the rate of at least 100 but not greater than 120 per minute, with minimal interruptions. AEDs are safe and successful when used in children older than 1 year. A single shock strategy using a non-escalating dose of 4 J/kg is recommended for defibrillation in children. Cuffed tubes can be used safely in infants and young children. Monitoring exhaled carbon dioxide (CO2), ideally by capnography, is recommended during resuscitation. RESUSCITATION OF BABIES AT BIRTH: For uncompromised babies, a delay in cord clamping of at least one minute from the complete delivery is now recommended. For term infants, air should be used fro resuscitation at birth. For preterm babies less than 32 weeks gestation blended oxygen and air should be given judiciously and its use guided by pulse oximetry. Preterm babies of less than 28 weeks gestation should be completely covered in a plastic wrap up to their necks, without drying, immediately after birth. The recommended compression: ventilation ratio remains at 3:1 for newborn resuscitation. Attempts to aspirate meconium from the nose and mouth of the unborn baby, while the head is still on the perineum, are not recommended. If adrenaline is given the n the intravenous route is recommended using a dose of 10-30 microg/kg. Newly born infants born at term or near-term with moderate to severe hypoxic-ischaemic encephalopathy should be treated with therapeutic hypothermia. PRINCIPLES OF EDUCATION IN RESUSCITATION: The aim is to ensure that learners acquire and retain skill and knowledge that will enable them to act correctly in actual cardiac arrest and improve patient outcome. Short video/computer self-instruction courses, with minimal or no instructor coaching, combined with hands-on practice can be considered as an effective alternative to instructor-led basic life support (BLS and AED) courses. Ideally all citizens should be trained in standard CPR that includes compressions and ventilations. Basic and advanced life support knowledge and skills deteriorate in as little as three to six months. CPR prompt or feedback devices improve CPR skill acquisition and retention.},
}

Acute Coronary Syndrome/therapy
Adult
Cardiopulmonary Resuscitation/*methods/standards
Child
*Emergency Medical Services
Humans
Infant, Newborn
Myocardial Infarction/therapy