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Results for “causality”

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PubMed2026

Exploring causal associations between autoimmune diseases and hearing loss: a mendelian randomization study.

OBJECTIVE: The causal relationship between Autoimmune Diseases (ADs) and Hearing Loss (HL) remains unclear. This study investigates whether genetic predispositions associated with ADs contribute to HL risk. METHODS: Mendelian Randomization (MR) analysis was conducted to explore the causal effects of ADs on HL. SNPs from Genome-Wide Association Studies (GWAS) were used as instrumental variables for ADs, including Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D), Systemic Lupus Erythematosus (SLE), Sjögren's Syndrome (SS), Ankylosing Spondylitis (AS), Multiple Sclerosis (MS), Crohn's Disease (CD), and Ulcerative Colitis (UC). Outcome data included Sensorineural Hearing Loss (SNHL), Conductive Hearing Loss (CHL), Mixed conductive and sensorineural Hearing Loss (MHL), and Sudden Idiopathic Hearing Loss (SIHL). MR analyses employed Inverse Variance Weighted (IVW) as the primary method, supplemented with MR-Egger, weighted median, and weighted mode. Heterogeneity, pleiotropy, and sensitivity were evaluated using Cochran's Q test, MR-Egger regression, MR-PRESSO, and leave-one-out analysis. RESULTS: The IVW method identified nine significant associations: MS-SIHL (OR = 1.0494, 95% CI 1.0072-1.0934), AS-CHL (OR = 1.2832, 95% CI 1.0643-1.5472), AS-MHL (OR = 1.5994, 95% CI 1.3696-1.8678), AS-SNHL (OR = 1.1903, 95% CI 1.1104-1.276), AS-SIHL (OR = 1.481, 95% CI 1.22-1.798), SLE-CHL (OR = 1.0593, 95% CI 1.0116-1.1092), UC-MHL (OR = 1.0907, 95% CI 1.0027-1.1865), CD-CHL (OR = 1.0529, 95%CI: 1.0074-1.1005), and CD-SIHL (OR = 1.0597, 95% CI 1.0177-1.1034). Among these, outliers were detected only in AS-SNHL. After outlier removal, the AS-SNHL association remained significant (OR = 1.1722, p < 0.00001), with resolved heterogeneity and pleiotropy. No heterogeneity and pleiotropy were found for the other associations. CONCLUSION: This study identified nine significant AD-HL associations, emphasizing the need for targeted screening and management of HL in individuals with AD. LEVEL OF EVIDENCE: Level 5.

Humans↗

PubMed2006

Causal relations drive young children's induction, naming, and categorization.

A number of recent models and experiments have suggested that evidence of early category-based induction is an artifact of perceptual cues provided by experimenters. We tested these accounts against the prediction that different relations (causal versus non-causal) determine the types of perceptual similarity by which children generalize. Young children were asked to label, to infer novel properties, and to project future appearances of a novel animal that varied in two opposite respects: (1) how much it looked like another animal whose name and properties were known, and (2) how much its parents looked like parents of another animal whose name and properties were known. When exemplar origins were known, children generalized to exemplars with similar origins rather than with similar appearances; when origins were unknown, children generalized to exemplars with similar appearances. Results indicate even young children possess the cognitive control to choose the similarities that best predict accurate generalizations.

Avoidance Learning↗

PubMed2006

Transcranial magnetic stimulation, causal structure-function mapping and networks of functional relevance.

Transcranial magnetic stimulation is now a well-established tool for inducing transient changes in brain activity non-invasively in conscious human volunteers. During the past couple of years, the ability to actively interfere with neural processing during behavioral performance has been used increasingly for the investigation of causal brain-behavior relationships in higher cognitive functions. The simultaneous combination of transcranial magnetic stimulation with methods of functional brain imaging, however, promises to be of especially great value for our understanding of the human brain, as it provides the opportunity to stimulate brain circuits while simultaneously monitoring changes in brain activity and behavior. Such an approach could help us to identify brain networks of functional relevance, and might enable causal brain-behavior inferences across the entire brain.

Behavior↗

PubMed2004

Inflammatory brain damage in preterm newborns--dry numbers, wet lab, and causal inferences.

Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.

Analysis of Variance↗

PubMed2026

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗

PubMed2006

The causal role of negative imagery in social anxiety: a test in confident public speakers.

This study tests the causal role of negative self-imagery in social anxiety. Low public-speaking anxious volunteers rehearsed a negative self-image, a positive self-image or a control image prior to giving a speech. As predicted, the negative image group felt more anxious, believed they performed less well and reported more negative thoughts than the positive image group. These findings do not appear to be due to changes in state anxiety, since they remained unchanged when anxiety was controlled in an analysis of covariance. The negative image group also reported more anxiety than the control group. Given that participants do not currently have anxiety problems, the findings are consistent with the idea that negative self-imagery has a causal role in the development and maintenance of social anxiety.

Affect↗

PubMed2005

A secret agent? How infants learn about the identity of objects in a causal scene.

Four experiments examined the role of correlations between dynamic and static parts on 12- to 16-month-olds' ability to learn the identity of agents and recipients in a simple causal event. Infants were habituated to events in which objects with a dynamic or static part acted as an agent or a recipient and then were tested with an event in which the part-causal role relations were switched. Experiment 1 revealed that 16-month-olds, but not 12-month-olds, associate a dynamic part with the role of agent and a static part with the role of recipient. Experiment 2 showed that 12- and 16-month-olds do not associate a static part with the role of agent or a dynamic part with the role of recipient. Experiment 3 demonstrated that 14-month-olds will learn the relations presented in Experiment 1 and Experiment 2. Experiment 4 revealed that 12-month-olds were able to discriminate the two geometric figures in the events. The results are discussed with respect to infants' developing ability to attend to correlations between dynamic and static cues and the mechanism underlying early object concept acquisition.

Cognition↗

PubMed2005

The causal effect of income on health: evidence from German reunification.

We investigate whether there was a causal effect of income changes on the health satisfaction of East and West Germans in the years following reunification. Our data source is the German Socio-Economic Panel (GSOEP) between 1984 and 2002, and we fit a recently proposed fixed-effects ordinal estimator to our health measures and use a causal decomposition technique to account for panel attrition. We find evidence of a significant positive effect of income changes on health satisfaction, but the quantitative size of this effect is small. This is the case with respect to current income and a measure of 'permanent' income.

Adult↗

PubMed2006

Turbulent urinary flow in the urethra could be a causal factor for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common form of prostate disease in middle-aged and elderly men, and leads to severe impairment later in life. Despite its significant impact on public health, the underlying cause of BPH is yet to be determined. This hypothesis proposes a new causal factor for BPH. Applying concepts of dynamics of fluids to the process of urination it could be stated that a turbulent urinary flow through the passage of the urethra. The turbulent urinary flow in the urethra applies pressure and stretch forces to the surrounding tissue. This stimulus repeated over time and coupled with age-related changes of the urethral tissue could contribute to the development of BPH. In support of this hypothesis, several mechanotransduction studies have shown that vibration and pressure forces applied to different cell tissues can provoke cellular and molecular changes. Another supportive data is the presence of the hyperplasic reaction surrounding the urethra specifically located in the transition zone, the only zone where BPH develops. It is crucial to identify causal factors to understanding the disease and to determine effective primary prevention strategies. Future studies of the dynamics of fluids in the urethra are warranted. The finding of significant forces transmitted to the periurethral tissue from a turbulent urinary flow could give us the clue to the underlying cause of BPH. If this hypothesis proves to be valid there are several primary prevention measures that could be implemented to impede the development of BPH. Educational intervention measures in younger populations to avoid frequent urinary retention and active urination (process of forcing the urine through the urethra at a high velocity) could be considered. Studies of the impact of turbulence in the standing vs. sitting position during urination in men should also be considered.

Aged↗

PubMed2006

An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspring.

This review is part of a series intended for non-specialists that will provide an overview of evidence for causal relationships between micronutrient deficiencies and brain function. Here, we review 34 studies in rodents linking the availability of choline during gestation and perinatal development to neurological function or performance of offspring in cognitive and behavioral tests. Experimental designs, major results, and statistical criteria are summarized in Tables 1-4. Based on our reading of the literature, the evidence suggests that choline supplementation during development results in improved performance of offspring in cognitive or behavioral tests, and in changes in a variety of neurological functional indicators: (1) enhanced performance was observed, particularly on more difficult tasks; (2) increases (choline supplementation) or decreases (choline deficiency) were observed in electrophysiological responsiveness and size of neurons in offspring; and (3) supplementation resulted in some protection against adverse effects of several neurotoxic agents (including alcohol) in offspring. Discussion topics include methodological issues, such as the importance of independent replication, causal criteria, and uncertainties in interpreting test results.

Animals↗

PubMed2006

Ictal source analysis: localization and imaging of causal interactions in humans.

We propose a new integrative approach to characterize the structure of seizures in the space, time, and frequency domains. Such characterization leads to a new technical development of ictal source analysis for the presurgical evaluation of epilepsy patients. The present new ictal source analysis method consists of three parts. First, a three-dimensional source scanning procedure is performed by a spatio-temporal FINE source localization method to locate the multiple sources responsible for the time evolving ictal rhythms at their onsets. Next, the dynamic behavior of the sources is modeled by a multivariate autoregressive process (MVAR). Lastly, the causal interaction patterns among the sources as a function of frequency are estimated from the MVAR modeling of the source temporal dynamics. The causal interaction patterns indicate the dynamic communications between sources, which are useful in distinguishing the primary sources responsible for the ictal onset from the secondary sources caused by the ictal propagation. The present ictal analysis strategy has been applied to a number of seizures from five epilepsy patients, and their results are consistent with observations from either MRI lesions or SPECT scans, which indicate its effectiveness. Each step of the ictal source analysis is statistically evaluated in order to guarantee the confidence in the results.

Brain↗

PubMed2004

Manipulating intent: evidence for a causal role of the superior colliculus in target selection.

The superior colliculus (SC) is well known for its role in the motor control of saccades. Recent work has shown that it also plays a role in the selection of saccades, but a causal role in the process of target selection has not been demonstrated. We applied subthreshold microstimulation to the SC while monkeys performed a task requiring them to select a stimulus as the target for a pursuit or saccade movement. Stimulation increased the proportion of selections toward the stimulus that appeared contralateral to the site of stimulation and also decreased their latencies. For pursuit, this stimulation-induced contralateral response bias was with respect to the initial target location and not the direction of eye movement, demonstrating a causal effect on target choice distinct from any effect on motor preparation. These results show that the SC helps decide the object of the next movement, beyond its traditional responsibility of saccade production.

Animals↗

PubMed2004

Infectious agents and cancer: criteria for a causal relation.

Infectious agents, mainly viruses, are among the few known causes of cancer and contribute to a variety of malignancies worldwide. The agents and cancers considered here are human papillomaviruses (cervical carcinoma); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B and hepatitis C viruses (hepatocellular carcinoma); Human T-cell Leukemia Virus-1 (T-cell leukemias); and helicobacter pylori (gastric carcinoma), which account for up to 20% of malignancies around the globe. The criteria most often used in determining causality are consistency of the association, either epidemiologic or on the molecular level, and oncogenicity of the agent in animal models or cell cultures. However use of these generally applied criteria in deciding on causality is selective, and the criteria may be weighted differently. Whereas for most of the tumor viruses the viral genome persists in an integrated or episomal form with a subset of viral genes expressed in the tumor cells, some agents (HBV, HCV, helicobacter) are not inherently oncogenic, but infection leads to transformation of cells by indirect means. For some malignancies the viral agent appears to serve as a cofactor (Burkitt's lymphoma-EBV; mesothelioma - SV(40)). For others the association is inconsistent (Hodgkin's Disease, gastric carcinomas, breast cancer-EBV) and may either define subsets of these malignancies, or the virus may act to modify phenotype of an established tumor, contributing to tumor progression rather than causing the tumor. In these cases and for the human polyomaviruses the association with malignancy is less consistent or still emerging. In contrast despite the potent oncogenic properties of some strains of human adenovirus in tissue culture and animals the virus has not been linked with any human cancers. Finally it is likely that more agents, most likely viruses, both known and unidentified, have yet to be implicated in human cancer. In the meantime study of tumorigenic infectious agents will continue to illuminate molecular oncogenic processes.

Animals↗

PubMed1998

Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii nigeriensis infection in Swiss mice.

The causal prophylactic activity of five tricyclic anti-histaminic agents (histamine H1-receptor antagonists) cyproheptadine, ketotifen, loratadine, azatadine and terfenadine was evaluated in an experimental murine malaria model. Sporozoite induced infections with Plasmodium yoelii nigeriensis (N-67), a strain innately resistant to choloroquine, were employed for the efficacy test and pyrimethamine and primaquine were used as standard reference drugs. Treatment with cyproheptadine or ketotifen at 5 mg/kg and terfenadine at 50 mg/kg, orally for 3 days (-1, 0, +1) completely prevented the establishment of patent infection in mice inoculated with 1 x 10(5) sporozoites on day 0. Partial activity was recorded with lower doses of the above agents as well as with azatadine and loratadine at 10 mg/kg as indicated by marginal delay in the development of patent infection after sporozoite challenge. None of these agents showed blood schizontocidal activity at doses found effective in the causal prophylactic test, though initial suppression of parasitaemia was observed with cyproheptadine and ketotifen at higher doses. This study is the first report on efficacy of antihistaminic agents for growth inhibition of pre-erythrocytic stages of any malaria parasite.

Animals↗

PubMed2003

Self-images play a causal role in social phobia.

Patients with social phobia often experience negative self-images in social situations. The current study investigated whether negative self-images have a causal role in maintaining social phobia. Patients with social phobia participated twice in a conversation with a stranger, once whilst holding their usual negative self-image in mind and once whilst holding a less negative (control) self-image in mind, with order counterbalanced across participants. Compared to the control image condition, when participants held the negative image in mind they experienced greater anxiety, rated their anxiety symptoms as being more visible, and rated their performance as poorer. An assessor who did not know which image was being held also rated participants' anxiety as more evident and their behaviour as less positive when the negative image was being held in mind. Finally, when participant and assessor ratings were compared, participants underestimated their performance and overestimated the visibility of their anxiety to a significantly greater extent in the negative imagery condition. Taken together, these results support the hypothesis that negative self-imagery has a causal role in maintaining social phobia.

Adult↗

PubMed2003

Maternal smoking during pregnancy and risk to boys' conduct disturbance: an examination of the causal hypothesis.

BACKGROUND: We undertook this study to determine whether the widely replicated link between maternal smoking and conduct disturbance (Cd) is better explained by a model of direct causation or of mother-offspring transmission of a latent Cd variable. METHODS: Family data collected on 538 adolescent twin boys from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to compare two alternative models: 1) a model composed of a latent transmissible factor that influences mother's juvenile conduct symptoms, smoking during pregnancy, and subsequent Cd and smoking in her adolescent boys; and 2) a model specifying a direct causal path from mother's smoking to child Cd. RESULTS: The maternal-offspring transmission model fit the data as well as a model specifying a direct causal path from maternal smoking to child Cd. CONCLUSIONS: Our results suggest that the association between maternal smoking during pregnancy and boys' Cd symptoms may be attributed to the transmission of a latent Cd factor and not to a direct effect of the smoking. Our results challenge previous findings of a direct effect of prenatal smoke exposure on risk to Cd once other etiologic factors are considered.

Adolescent↗

PubMed2000

Causal status effect in children's categorization.

The current study examined the causal status effect (weighing cause features more than effect features in categorization) in children. Adults (Study 1) and 7-9-year-old children (Study 2) learned descriptions of novel animals, in which one feature caused two other features. When asked to determine which transfer item was more likely to be an example of the animal they had learned, both adults and children preferred an animal with a cause feature and an effect feature rather than an animal with two effect features. This study is the first direct demonstration of the causal status effect in children.

Adult↗

PubMed2004

Is there a causal link from phonological awareness to success in learning to read?

In this review, we re-assess the evidence that phonological awareness represents a skill specific to spoken language that precedes and directly influences the process of reading acquisition. Longitudinal and experimental training studies are examined in detail, as these are considered most appropriate for exploring a causal hypothesis of this nature. A particular focus of our analysis is the degree to which studies to date have controlled for existing literacy skills in their participants and the influence that these skills might have on performance on phonological awareness tasks. We conclude that no study has provided unequivocal evidence that there is a causal link from competence in phonological awareness to success in reading and spelling acquisition. However, we believe that such a study is possible and outline some ideas for its design and implementation.

Awareness↗