docling/tests/data/groundtruth/docling_v2/10-1055-a-2313-0311.nxml.itxt

item-0 at level 0: unspecified: group _root_
  item-1 at level 1: title: Exploring the Two-Way Link betwe ... o-Sample Mendelian Randomization Study
  item-2 at level 1: paragraph: Yang Wang; Vascular Surgery, Sha ... iliated Central Hospital, Jinan, China
  item-3 at level 1: text: Background The objective of this ... nd VTE within the European population.
  item-4 at level 1: section_header: Introduction
    item-5 at level 2: text: Venous thromboembolism (VTE) enc ... risk in clinical settings are crucial.
    item-6 at level 2: text: Migraine, characterized by recur ... elationship between VTE and migraines.
    item-7 at level 2: text: Mendelian randomization (MR) is  ... n traditional epidemiological methods.
  item-8 at level 1: section_header: Research Methodology
    item-9 at level 2: text: A rigorous bidirectional two-sam ... of the resultant causal inferences. 12
  item-10 at level 1: section_header: Data Sources
    item-11 at level 2: text: Our SNPs are obtained from large ... in our study can be found in Table 1 .
    item-12 at level 2: text: The variances in genetic variati ... ecessity for further ethical approval.
  item-13 at level 1: section_header: Filtering Criteria of IVs
    item-14 at level 2: text: To select appropriate SNPs as IV ... 0 to minimize weak instrument bias. 19
  item-15 at level 1: section_header: Results
    item-16 at level 2: text: In the present investigation, we ... analysis results detailed in Table 2 .
  item-17 at level 1: section_header: Mendelian Randomization Analysis
    item-18 at level 2: text: During the IV screening process, ... ined in our investigation ( Fig. 2D ).
  item-19 at level 1: section_header: Reverse Mendelian Randomization Analysis
    item-20 at level 2: text: Upon screening for IVs in migrai ... e estimated causal effect ( Fig. 3D ).
  item-21 at level 1: section_header: Discussion
    item-22 at level 2: text: VTE constitutes a grave health h ... he MR analysis is considered reliable.
    item-23 at level 2: text: Our MR analysis discloses a pote ... s in clinical practice is recommended.
    item-24 at level 2: text: Our endeavor seeks to offer a pr ... rely a weak risk factor for migraines.
  item-25 at level 1: section_header: Tables
  item-27 at level 1: table with [3x6]
    item-27 at level 2: caption: Table 1 Description of GWAS used for each phenotype
  item-29 at level 1: table with [4x7]
    item-29 at level 2: caption: Table 2 Mendelian randomization regression causal association results
  item-30 at level 1: section_header: Figures
  item-32 at level 1: picture
    item-32 at level 2: caption: Fig. 1 This figure illustrates the research methodology for the bidirectional Mendelian randomization analysis concerning migraine and VTE. Assumption I: relevance assumption; Assumption II: independence/exchangeability assumption; Assumption III: exclusion restriction assumption.
  item-34 at level 1: picture
    item-34 at level 2: caption: Fig. 2 This figure explores the correlation between migraine risk and VTE, validating the presence of heterogeneity and pleiotropy. (A) The forest plot displays individual IVs, with each point flanked by lines that depict the 95% confidence interval. The effect of SNPs on the exposure (migraine) is shown along thex-axis, whereas their impact on the outcome (VTE) is presented on they-axis. A fitted line reflects the Mendelian randomization analysis results. (B) A scatter plot visualizes each IV, with the SNP effects on both exposure and outcome similar to that of the forest plot. Again, a fitted line represents the Mendelian randomization results. (C) The funnel plot positions the coefficient βIVfrom the instrumental variable regression on thex-axis to demonstrate the association's strength, while the inverse of its standard error (1/SEIV†) on they-axis indicates the precision of this estimate. (D) A leave-one-out sensitivity analysis is shown on thex-axis, charting the estimated effects from the Mendelian randomization analysis. With each SNP associated with migraine successively excluded, the analysis recalculates the Mendelian randomization effect estimates, culminating with the “all” category that encompasses all considered SNPs. IV, instrumental variable; SNP, single nucleotide polymorphisms; VTE, venous thromboembolism; SE, standard error.†SE is the standard error of β.
  item-36 at level 1: picture
    item-36 at level 2: caption: Fig. 3 (A–D) This figure presents the relationship between VTE risk and migraine, also verifying heterogeneity and pleiotropy through similar graphic representations as detailed forFig. 2, but with the exposure and outcome reversed—SNPs' effect on VTE and outcome on migraine. SNP, single nucleotide polymorphisms; VTE, venous thromboembolism.
  item-37 at level 1: section_header: References
  item-38 at level 1: list: group list
    item-39 at level 2: list_item: F Khan; T Tritschler; S R Kahn;  ...  Venous thromboembolism. Lancet (2021)
    item-40 at level 2: list_item: J A Heit. Epidemiology of venous thromboembolism. Nat Rev Cardiol (2015)
    item-41 at level 2: list_item: . Headache Classification Commit ... rders, 3rd edition. Cephalalgia (2018)
    item-42 at level 2: list_item: K Adelborg; S K Szépligeti; L Ho ... based matched cohort study. BMJ (2018)
    item-43 at level 2: list_item: K P Peng; Y T Chen; J L Fuh; C H ... tionwide cohort study. Headache (2016)
    item-44 at level 2: list_item: S Sacco; A Carolei. Burden of at ... tients with migraine. Neurology (2009)
    item-45 at level 2: list_item: A R Folsom; P L Lutsey; J R Misi ... dults. Res Pract Thromb Haemost (2019)
    item-46 at level 2: list_item: I Y Elgendy; S E Nadeau; C N Bai ... ease in women. J Am Heart Assoc (2019)
    item-47 at level 2: list_item: C A Emdin; A V Khera; S Kathiresan. Mendelian randomization. JAMA (2017)
    item-48 at level 2: list_item: T Karlsson; F Hadizadeh; M Rask- ... n analyses. Arthritis Rheumatol (2023)
    item-49 at level 2: list_item: T Lawler; S Warren Andersen. Ser ... andomization studies. Nutrients (2023)
    item-50 at level 2: list_item: S Burgess; A S Butterworth; J R  ... ic predictors. J Clin Epidemiol (2016)
    item-51 at level 2: list_item: C Sudlow; J Gallacher; N Allen.  ... of middle and old age. PLoS Med (2015)
    item-52 at level 2: list_item: M S Lyon; S J Andrews; B Elswort ... summary statistics. Genome Biol (2021)
    item-53 at level 2: list_item: M I Kurki; J Karjalainen; P Palt ... ped isolated population. Nature (2023)
    item-54 at level 2: list_item: E Sanderson; M M Glymour; M V Ho ... zation. Nat Rev Methods Primers (2022)
    item-55 at level 2: list_item: J R Staley; J Blackshaw; M A Kam ... pe associations. Bioinformatics (2016)
    item-56 at level 2: list_item: M A Kamat; J A Blackshaw; R Youn ... pe associations. Bioinformatics (2019)
    item-57 at level 2: list_item: S Burgess; S G Thompson. Mendeli ... erence Using Genetic Variants.  (2021)
    item-58 at level 2: list_item: A May; L H Schulte. Chronic migr ... s and treatment. Nat Rev Neurol (2016)
    item-59 at level 2: list_item: D W Dodick. Migraine. Lancet (2018)
    item-60 at level 2: list_item: A A Khorana; N Mackman; A Falang ... boembolism. Nat Rev Dis Primers (2022)
    item-61 at level 2: list_item: E J Bell; A R Folsom; P L Lutsey ... alysis. Diabetes Res Clin Pract (2016)
    item-62 at level 2: list_item: S Bhoelan; J Borjas Howard; V Ti ... study. Res Pract Thromb Haemost (2022)
    item-63 at level 2: list_item: V Pengo; G Denas. Antiphospholip ... boembolism. Semin Thromb Hemost (2023)
    item-64 at level 2: list_item: L Maitrot-Mantelet; M H Horellou ... tional French study. Thromb Res (2014)
    item-65 at level 2: list_item: G E Tietjen; S A Collins. Hypercoagulability and migraine. Headache (2018)
    item-66 at level 2: list_item: J Schwaiger; S Kiechl; H Stockne ... tients with migraine. Neurology (2008)
    item-67 at level 2: list_item: C D Bushnell; M Jamison; A H Jam ... n based case-control study. BMJ (2009)
    item-68 at level 2: list_item: W Y Ding; M B Protty; I G Davies ... al fibrillation. Cardiovasc Res (2022)
    item-69 at level 2: list_item: R M Gupta; J Hadaya; A Trehan. A ... othelin-1 gene expression. Cell (2017)
    item-70 at level 2: list_item: B Kumari; A Prabhakar; A Sahu. E ... lation. Clin Appl Thromb Hemost (2017)
    item-71 at level 2: list_item: Y Zhang; J Liu; W Jia. AGEs/RAGE ... thrombosis (DVT). Bioengineered (2021)
    item-72 at level 2: list_item: J Padilla; A J Carpenter; N A Da ... Am J Physiol Heart Circ Physiol (2018)
    item-73 at level 2: list_item: L Liu; C Jouve; J Sebastien Hulo ... th muscle cells. Cardiovasc Res (2022)
    item-74 at level 2: list_item: R Vormittag; P Bencur; C Ay. Low ... romboembolism. J Thromb Haemost (2007)
    item-75 at level 2: list_item: H Chun; J H Kurasawa; P Olivares ... plex contacts. J Thromb Haemost (2022)