-
The Ocular Surface Apr 2024Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid...
PURPOSE
Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics.
METHODS
In this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at -80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h) of cytokine concentrations was analyzed.
RESULTS
90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1β (82.2%) and monocyte chemoattractant protein 1 (68.2%).
CONCLUSIONS
The tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease.
Topics: Humans; Tears; Male; Cytokines; Prospective Studies; Female; Adult; Middle Aged; Twins, Dizygotic; Twins, Monozygotic; Young Adult; Biomarkers; Aged
PubMed: 38387783
DOI: 10.1016/j.jtos.2024.02.005 -
Acta Ophthalmologica Jun 2024To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and...
PURPOSE
To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and environmental variation to WLR in healthy adults.
METHODS
This cross-sectional twin study included 78 monozygotic and 67 dizygotic same-sex twin pairs aged 58.4 ± 9.8 (mean ± SD) years. Lumen diameter (LD) and outer diameter (OD) of a superotemporal retinal artery were measured using adaptive optics fundus photography, and the WLR was calculated. Linear mixed model regression analysis of associations with WLR comprised the descriptive variables ocular axial length (AL), intraocular pressure (IOP), height, weight, body mass index (BMI), smoking, blood pressure, high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins, total cholesterol and triglycerides. The relative influence of genes and environment on WLR was calculated through polygenetic modelling.
RESULTS
Increasing age and arterial blood pressure were associated with a higher WLR, while increasing retinal artery OD and ocular AL were associated with a lower WLR. Sex, smoking status, BMI, IOP, cholesterol levels or triglycerides had no detectable impact on the WLR. Broad-sense heritability of WLR was 21% (95% CI: 1-41%), while environmental factors accounted for the remaining 79% of the interindividual variance (95% CI: 59-99%).
CONCLUSION
Retinal artery wall thickness was closely linked to increasing age and higher arterial blood pressure, the latter being mediated by the environment over genes.
Topics: Aged; Female; Humans; Male; Middle Aged; Axial Length, Eye; Blood Pressure; Cross-Sectional Studies; Intraocular Pressure; Retinal Artery; Twins, Dizygotic; Twins, Monozygotic
PubMed: 37702272
DOI: 10.1111/aos.15755 -
PloS One 2023Although genetics is known to have a role in sickness absences (SA), disability pensions (DP) and in their mutual associations, the empirical knowledge is scarce on not...
Although genetics is known to have a role in sickness absences (SA), disability pensions (DP) and in their mutual associations, the empirical knowledge is scarce on not having these interruptions, i.e., sustainable working life. Hence, we aimed to investigate how genetic and environmental factors affect individual variation in sustainable working life in short-term (two consecutive years) and in long-term (22 years of follow-up) using the classical twin modeling based on different genetic relatedness of mono- and dizygotic twins. The final sample (n = 51 071) included Swedish same-sex twins with known zygosity born between 1930 and 1990 (53% women) with complete national register data of employment, SA, DP, unemployment, old-age pension, emigration, and death. For the short-term sustainable working life, genetic factors explained 36% (95% confidence intervals (CI) 31-41%), environmental factors shared by co-twins such as family background 8% (95% CI 5-14%) and environmental factors unique to each twin individual 56% (95% CI 56-56%) on the individual differences. For the long-term sustainable working life, the largest proportions on individual differences were explained by environmental factors shared by co-twins (46%, 95% CI 44-48%) and unique to each twin individual (37% 95% CI 36-38%) whereas a small proportion was explained by genetic factors (18%, 95%CI 14-22%). To conclude, short-term sustainable working life was explained to a large extent by unique environment and to lesser extent by genetic factors whereas long-term (22 years) sustainable working life had both moderate unique and common environmental effect, and to lower extent genetic effects contributing to individual differences. These findings suggest that sustainable working life have different short- and long-term predictors.
Topics: Humans; Female; Male; Cohort Studies; Sweden; Individuality; Sick Leave; Twins, Dizygotic; Pensions
PubMed: 37498854
DOI: 10.1371/journal.pone.0289074 -
Psychology of Addictive Behaviors :... Feb 2024The purpose of our study was to provide a more rigorous test of the causal hypothesis that chronic alcohol use impairs working memory performance.
OBJECTIVE
The purpose of our study was to provide a more rigorous test of the causal hypothesis that chronic alcohol use impairs working memory performance.
METHOD
We measured linear associations between a latent factor representing alcohol consumption and accuracy across four working memory tasks before and after accounting for familial confounding using a cotwin control design. Specifically, this study examined accuracy through a latent working memory score, the National Institutes of Health (NIH) Toolbox List Sorting, NIH Toolbox Picture Sequence, Penn Word Memory, and 2-back tasks. The study included data from 158 dizygotic and 278 monozygotic twins ( = 29 ± 3 years).
RESULTS
In our initial sample-wide analysis, we did not detect any statistically significant associations between alcohol use and working memory accuracy. However, our cotwin control analyses showed that twins with greater levels of alcohol use exhibited worse scores on the latent working memory composite measure ( = -.25, CI [-.43, -.08], < .01), Picture Sequence ( = -.31, CI [-.55, -.08], < .01), and List Sorting ( = -.28, CI [-.51, -.06 ], = .01) tasks than did their cotwins.
CONCLUSIONS
These results are consistent with a potentially causal relationship between alcohol use and working memory performance that can be detected only after accounting for confounding familial factors. This highlights the importance of understanding the mechanisms that may underlie negative associations between alcohol use and cognitive performance, as well as the potential factors that influence both alcohol behaviors and cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Adult; Humans; Alcohol Drinking; Cognition; Ethanol; Memory, Short-Term; Twins
PubMed: 37326533
DOI: 10.1037/adb0000936 -
Human Brain Mapping Nov 2023We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual...
We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual differences on the functional connectivity of the brain using 65 monozygotic and 65 dizygotic healthy young adult twin pairs' low-frequency oscillation resting state functional Magnetic Resonance Imaging (fMRI) data from the Human Connectome Project. Overall, we found high number of genetically-influenced functional (GIF) connections involving posterior to posterior brain regions (occipital/temporal/parietal) implicated in low-level processes such as vision, perception, motion, categorization, dorsal/ventral stream visuospatial, and long-term memory processes, as well as high number across midline brain regions (cingulate) implicated in attentional processes, and emotional responses to pain. We found low number of GIF connections involving anterior to anterior/posterior brain regions (frontofrontal > frontoparietal, frontotemporal, frontooccipital) implicated in high-level processes such as working memory, reasoning, emotional judgment, language, and action planning. We found very low number of GIF connections involving subcortical/noncortical networks such as basal ganglia, thalamus, brainstem, and cerebellum. In terms of sex-specific individual differences, individual differences in males were more genetically influenced while individual differences in females were more environmentally influenced in terms of the interplay of interactions of Task positive networks (brain regions involved in various task-oriented processes and attending to and interacting with environment), extended Default Mode Network (a central brain hub for various processes such as internal monitoring, rumination, and evaluation of self and others), primary sensorimotor systems (vision, audition, somatosensory, and motor systems), and subcortical/noncortical networks. There were >8.5-19.1 times more GIF connections in males than females. These preliminary (young adult cohort-specific) findings suggest that individual differences in the resting state brain may be more genetically influenced in males and more environmentally influenced in females; furthermore, standard approaches may suggest that it is more substantially nonadditive genetics, rather than additive genetics, which contribute to the differences in sex-specific individual differences based on this young adult (male and female) specific cohort. Finally, considering the preliminary cohort-specific results, based on standard approaches, environmental influences on individual differences may be substantially greater than that of genetics, for either sex, frontally and brain-wide. [Correction added on 10 May 2023, after first online publication: added: functional Magnetic Resonance Imaging. Added: individual differences in, twice. Added statement between furthermore … based on standard approaches.].
Topics: Female; Humans; Male; Young Adult; Basal Ganglia; Brain; Brain Mapping; Connectome; Magnetic Resonance Imaging; Nerve Net; Thalamus; Twins, Dizygotic
PubMed: 36537283
DOI: 10.1002/hbm.25947 -
Cerebral Cortex (New York, N.Y. : 1991) Nov 2023Similarities between twins have been widely demonstrated, underscoring the remarkable influence of genetics across numerous traits. In this study, we explore the genetic...
Similarities between twins have been widely demonstrated, underscoring the remarkable influence of genetics across numerous traits. In this study, we explore the genetic underpinnings of the human brain by examining MRI data from the Queensland Twin Imaging study. Specifically, this study seeks to compare brain structure and function between twins and unrelated subjects, with an emphasis on describing the effects of genetic factors. To achieve these goals, we employed the source-based morphometry method to extract intrinsic components and elucidate recognizable patterns. Our results show that twins exhibit a higher degree of similarity in gray and white matter density compared with unrelated individuals. In addition, four distinct states of brain activity were identified using coactivation patterns analysis. Furthermore, twins demonstrated a greater degree of similarity in the temporal and spatial features of each state compared with unrelated subjects. Taken together, these results support the hypothesis that twins show greater similarity in both brain structure and dynamic functional brain activity. Further exploration of these methods may advance our understanding of the complex interplay between genes, environment, and brain networks.
Topics: Humans; Magnetic Resonance Imaging; Twins; Brain; White Matter; Head; Twins, Monozygotic; Twins, Dizygotic
PubMed: 37771046
DOI: 10.1093/cercor/bhad345 -
BMC Pregnancy and Childbirth May 2024To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived... (Comparative Study)
Comparative Study
Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.
OBJECTIVE
To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally.
METHODS
We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally.
RESULT
MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05).
CONCLUSION
Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.
Topics: Humans; Female; Pregnancy; Pregnancy, Twin; Reproductive Techniques, Assisted; Pregnancy Outcome; Retrospective Studies; Adult; Twins, Monozygotic; Chorion; Premature Birth; Twins, Dizygotic; Infant, Newborn; Placenta Previa
PubMed: 38698326
DOI: 10.1186/s12884-024-06521-z -
Journal of Oral Rehabilitation Jan 2024Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or...
BACKGROUND
Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self-reported sleep bruxism was correlated longitudinally, pairwise and cross-twin over a 20-year period.
OBJECTIVES
Self-reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same-sex twins born 1945-1957.
METHODS
We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross-sectional zygosity correlations and the zygosity-specific cross-twin cross-time correlations.
RESULTS
Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross-twin cross-time correlations were higher in MZ twins than in DZ twins, but less than the cross-sectional MZ and DZ pairwise correlations.
CONCLUSIONS
The higher correlation of reported sleep bruxism in the cross-twin cross-time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women.
Topics: Female; Humans; Male; Cohort Studies; Cross-Sectional Studies; Diseases in Twins; Self Report; Sleep Bruxism; Twins, Dizygotic; Twins, Monozygotic
PubMed: 36062358
DOI: 10.1111/joor.13368 -
Human Reproduction (Oxford, England) Jan 2024Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins?
SUMMARY ANSWER
We identified four new loci, GNRH1, FSHR, ZFPM1, and IPO8, in addition to previously identified loci, FSHB and SMAD3.
WHAT IS KNOWN ALREADY
The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures.
STUDY DESIGN, SIZE, DURATION
We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Over 700 000 mothers of DZ twins, twin individuals and singletons from large cohorts in Australia/New Zealand, Europe, and the USA were carefully screened to exclude twins born after use of ARTs. Genetic association analyses by cohort were followed by meta-analysis, phenome wide association studies (PheWAS), in silico and in vivo annotations, and Zebrafish functional validation.
MAIN RESULTS AND THE ROLE OF CHANCE
This study enlarges the sample size considerably from previous efforts, finding four genome-wide significant loci, including two novel signals and a further two novel genes that are implicated by gene level enrichment analyses. The novel loci, GNRH1 and FSHR, have well-established roles in female reproduction whereas ZFPM1 and IPO8 have not previously been implicated in female fertility. We found significant genetic correlations with multiple aspects of female reproduction and body size as well as evidence for significant selection against DZ twinning during human evolution. The 26 top single nucleotide polymorphisms (SNPs) from our GWAMA in European-origin participants weakly predicted the crude twinning rates in 47 non-European populations (r = 0.23 between risk score and population prevalence, s.e. 0.11, 1-tail P = 0.058) indicating that genome-wide association studies (GWAS) are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. In vivo functional tests in zebrafish for IPO8 validated its essential role in female, but not male, fertility. In most regions, risk SNPs linked to known expression quantitative trait loci (eQTLs). Top SNPs were associated with in vivo reproductive hormone levels with the top pathways including hormone ligand binding receptors and the ovulation cycle.
LARGE SCALE DATA
The full DZT GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/).
LIMITATIONS, REASONS FOR CAUTION
Our study only included European ancestry cohorts. Inclusion of data from Africa (with the highest twining rate) and Asia (with the lowest rate) would illuminate further the biology of twinning and female fertility.
WIDER IMPLICATIONS OF THE FINDINGS
About one in 40 babies born in the world is a twin and there is much speculation on why twinning runs in families. We hope our results will inform investigations of ovarian response in new and existing ARTs and the causes of female infertility.
STUDY FUNDING/COMPETING INTEREST(S)
Support for the Netherlands Twin Register came from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.NL, 184.021.007), Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB, European Research Council (ERC-230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1) and the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951. The QIMR Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). L.Y. is funded by Australian Research Council (Grant number DE200100425). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886) and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). The Women's Genome Health Study (WGHS) was funded by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with support for genotyping provided by Amgen. Data collection in the Finnish Twin Registry has been supported by the Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, AA-09203, AA15416, and K02AA018755) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073 and 336823 to J. Kaprio). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002), the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. Work in the Del Bene lab was supported by the Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01). C.R. was supported by an EU Horizon 2020 Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF-2014 #661527). H.S. and K.S. are employees of deCODE Genetics/Amgen. The other authors declare no competing financial interests.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Animals; Female; Humans; Pregnancy; Carrier Proteins; Fertility; Genome-Wide Association Study; Hormones; Proteins; Twinning, Dizygotic; United States; Zebrafish
PubMed: 38052102
DOI: 10.1093/humrep/dead247 -
Journal of Neurosurgery. Spine Apr 2024Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is... (Review)
Review
OBJECTIVE
Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members.
METHODS
This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included.
RESULTS
Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%).
CONCLUSIONS
Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.
PubMed: 38608294
DOI: 10.3171/2024.1.SPINE231277