Recommending research articles: A multi-level chronological learning-based approach using unsupervised keyphrase extraction and lexical similarity calculation

A research article recommendation approach aims to recommend appropriate research articles to analogous researchers to help them better grasp a new topic in a particular research area. Due to the accessibility of research articles on the web, it is tedious to recommend a relevant article to a researcher who strives to understand a particular article. Most of the existing approaches for recommending research articles are metadata-based, citation-based, bibliographic coupling-based, content-based, and collaborative filtering-based. They require a large amount of data and do not recommend reference articles to the researcher who wants to understand a particular article going through the reference articles of that particular article. Therefore, an approach that can recommend reference articles for a given article is needed. In this paper, a new multi-level chronological learning-based approach is proposed for recommending research articles to understand the topics/concepts of an article in detail. The proposed method utilizes the TeKET keyphrase extraction technique, among other unsupervised techniques, which performs better in extracting keyphrases from the articles. Cosine and Jaccard similarity measures are employed to calculate the similarity between the parent article and its reference articles using the extracted keyphrases. The cosine similarity measure outperforms the Jaccard similarity measure for finding and recommending relevant articles to understand a particular article. The performance of the recommendation approach seems satisfactory, with an NDCG value of 0.87. The proposed approach can play an essential role alongside other existing approaches to recommend research articles. Autho

A genome-wide association study of outcome from traumatic brain injury

Background Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias. Methods We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography. Findings The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10−8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10−5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10−4). Interpretation While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.Additional co-authors: Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, and David K. Menon on behalf of The Genetic Associations In Neurotrauma (GAIN) Consortium (with contribution from the CENTER-TBI, TRACK-TBI, CABI, MGB, and TBIcare studies

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies

Cerebrovascular Injuries in Traumatic Brain Injury

Traumatic brain injury is a complex and highly heterogeneous disease due to the host of concomitant injuries that may accompany the initial insult. Due to the dynamic interplay between the injuries that may arise, the management of these injuries is challenging. In a small subset of patients with traumatic brain injury, cerebral vascular injury may occur, which presents its own diagnostic and therapeutic challenges. These vascular injuries often present in a delayed fashion, thereby going unnoticed by clinicians. Early recognition and treatment of these injuries is crucial, given their high morbidity and mortality. Through a critical review of the literature, we present the spectrum of cerebrovascular injuries that may occur with traumatic brain injury and discuss classification systems that are used to stratify cerebrovascular injury. We then focus on the diagnosis of cerebral vascular injury using different neuroimaging modalities. Lastly, we explore the treatment of these injuries ranging from antiplatelet therapies to endovascular and open vascular procedures. By highlighting the pitfalls and challenges of this complex disease, we hope to provide clinicians with the framework to recognize and treat vascular injuries that are seen in patients with traumatic brain injury

The impact of age and severity on dementia after traumatic brain injury: a comparison study

Background: Growing evidence associates traumatic brain injury (TBI) with increased risk of dementia, but few studies have evaluated associations in patients younger than 55 yr using non-TBI orthopedic trauma (NTOT) patients as controls to investigate the influence of age and TBI severity, and to identify predictors of dementia after trauma. Objective: To investigate the relationship between TBI and dementia in an institutional group. Methods: Retrospective cohort study (2000-2018) of TBI patients aged 45 to 100 yr vs NTOT controls. Primary outcome was dementia after TBI (followed 6410 yr). Cox proportional hazards models were used to assess risk of dementia; logistic regression models assessed predictors of dementia. Results: Among 24 846 patients, TBI patients developed dementia (7.5% vs 4.6%) at a younger age (78.6 vs 82.7 yr) and demonstrated higher 10-yr mortality than controls (27% vs 14%; P &lt; .001). Mild TBI patients had higher incidence of dementia (9%) than moderate/severe TBI (5.4%), with lower 10-yr mortality (20% vs 31%; P &lt; .001). Risk of dementia was significant in all mild TBI age groups, even 45 to 54 yr (hazard ratio 4.1, 95% CI 2.7-7.8). A total of 10-yr cumulative incidence was higher in mild TBI (14.4%) than moderate/severe TBI (11.3%) and controls (6.8%) (P &lt; .001). Predictors of dementia include TBI, sex, age, hypertension, hyperlipidemia, stroke, depression, anxiety, and Injury Severity Score. Conclusion: Mild and moderate/severe TBI patients experienced higher incidence of dementia, even in the youngest group (45-54 yr old), than NTOT controls. All TBI patients, especially middle-aged adults with minor injury who are more likely to be overlooked, should be monitored for dementia

Whole genome sequencing association and gene-by-air-pollution interaction analyses identified kitlg as a novel baseline lung function gene candidate among African American children with asthma

RATIONALE: Baseline lung function, quantified as the forced expiratory volume in the first second of exhalation (FEV1), is a standard diagnostic criterion used by clinicians to identify and classify lung diseases. FEV1 is a complex phenotype that is heavily influenced by both environmental and genetic factors, with estimated heritability as high as 55%. Epidemiological studies have shown that early-life exposure to air pollution is a significant predictor of baseline lung function, while several genetic loci have been associated with FEV1 and genetic ancestry contributes to its variation. Despite numerous studies linking genetic and environmental factors to variation in FEV1, the majority of its heritability remains unexplained. We hypothesized that a portion of this missing heritability is due to gene-by-environment (GxE) interactions. METHODS: Using whole genome sequencing data on 876 African American children with asthma from the Trans-Omics for Precision Medicine (TOPMed) program, we performed a genome-wide association study of FEV1 using the ENCORE tool. Potential gene targets of associated variants were identified using long range chromatin interaction data available in the HUGIN browser. RNA-Seq data of nasal epithelial cells from minority children with asthma was used to identify eQTLs of potential gene targets. FEV1-associated variants were overlapped with candidate cisregulatory elements (ccRE) from ENCODE to identify variants with potential regulatory function. Gene-by-air pollution analyses using early-life and past-year exposure to air pollution were performed. All models were adjusted for age, sex, height, the first five genetic principal components, use of controller medications and sequencing batches. RESULTS AND CONCLUSION: We identified a novel genome-wide significant locus on chromosome 12 (rs73429450) that was associated with FEV1 (p = 1.26 x 10-8, β =0.302). Publicly available Hi-C and in-house eQTL data supported a regulatory role of the novel locus on the KITLG gene. Additional gene-by-air-pollution interaction analyses found that candidate variants interacted with SO2 in the first year of life (rs73440122, p = 0.049, β = 0.009) and past-year exposure (rs58475486, p = 0.003, β = 0.539) to modify association with FEV1. Thus, we identified KITLG as a novel gene candidate with variants that have protective genetic association and gene-by-SO2 interactions with baseline lung function (FEV1) among African American children with asthma

A genome-wide association study of outcome from traumatic brain injury

Background: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias. Methods: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography. Findings: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10−8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10−5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10−4). Interpretation: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

A genome-wide association study of outcome from traumatic brain injury.

BackgroundFactors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.MethodsWe performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FindingsThe estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p &lt; 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p &lt; 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).InterpretationWhile multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section