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PubMed2006

Cognitive insight and causal attribution in the development of self-stigma among individuals with schizophrenia.

OBJECTIVE: Stigma has dampening effects on the overall rehabilitation of individuals given a diagnosis of schizophrenia. This study was an initial attempt to understand the relationship between cognitive insight and attribution in the development of self-stigma among this group of mental health consumers. METHODS: In a cross-sectional design, the investigators interviewed 162 mental health consumers with broad diagnoses of schizophrenia from 15 community-based psychiatric rehabilitation centers in Hong Kong. After controlling for the effects of demographic and illness-related factors, the authors used hierarchical multiple regression analysis to investigate the effects of cognitive insight and causal attribution on self-stigma. RESULTS: Better cognitive insight and attribution of personal responsibility to the cause of the illness were significantly associated with higher levels of self-stigma. CONCLUSIONS: Given that awareness and interpretation of participants' illness were related to self-stigma, cognitive restructuring is needed to alleviate self-stigma among individuals with schizophrenia.

Adolescent↗
PubMed1999

The relationship of causal beliefs and contact with users of mental health services to attitudes to the 'mentally ill'.

Programmes to destigmatise 'mental illness' have traditionally been based on the 'mental illness is an illness like any other' metaphor and have been largely unsuccessful. By measuring attitudes towards, and etiology beliefs about, 'mental illness' before and after a series of four undergraduate lectures presenting the psychosocial causes of, and solutions to, severe mental health problems, this study (a) replicated previous studies demonstrating a relationship between biogenetic causal beliefs and negative attitudes towards 'mental patients'; (b) found that following the lectures attitudes improved, particularly around the key variables of dangerousness and unpredictability; and (c) demonstrated that amount of contact with people who had received psychiatric treatment was an even stronger predictor of positive attitudes than acceptance of a psychosocial perspective.

Adolescent↗
PubMed2025

From genetic causality to druggable targets: A multiomics framework identifies ZSCAN16 in gout pathogenesis.

ObjectiveGout is a prevalent form of inflammatory arthritis in which many patients respond suboptimally to current therapies. Drug development is hampered by a lack of genetically validated targets, leading to high clinical trial attrition. This study aimed to systematically identify and prioritize novel, druggable targets for gout via a multilayered genetic and functional genomics approach.MethodsWe performed two-sample Mendelian randomization (MR) using cis-expression quantitative trait locus (cis-eQTL) data and dual independent gout genome-wide association study (GWAS) cohorts (openGWAS and FinnGen). The candidate genes were subjected to a rigorous validation pipeline including Bayesian colocalization, phenome-wide association studies (PheWASs) to assess pleiotropy and on-target safety, and single-cell RNA sequencing (scRNA-seq) to delineate the cellular context. Molecular docking was used to evaluate the structural druggability of prioritized targets.ResultsMR analysis revealed 15 genes causally associated with gout. Colocalization analysis (PPH4 > 0.8) prioritized two targets: ZSCAN16 (risk-increasing, OR = 1.04, 95% CI [1.02-1.06]) and TRIM10 (protective, OR = 0.96, 95% CI [0.94-0.98]). Crucially, PheWAS revealed that ZSCAN16 is highly specific to gout, whereas TRIM10 exhibited extensive pleiotropy with hematological and cardiometabolic traits, indicating significant safety risks. Single-cell analysis provided orthogonal validation, demonstrating flare-specific upregulation of ZSCAN16 in cytotoxic T/NK cells. Molecular docking confirmed ZSCAN16 as a structurally druggable target, showing high-affinity binding with known compounds (e.g. digoxin, binding energy = -9.6 kcal/mol).ConclusionsOur study identifies ZSCAN16 as a high-potential, druggable therapeutic target for gout, highlighting its genetic influence on specific immune cell activities during acute flares. Conversely, TRIM10 was deprioritized owing to substantial pleiotropic liabilities and poor chemical tractability. These findings suggest that ZSCAN16 could play a crucial role in the pathogenesis of gout and may provide a valuable lead for future drug discovery efforts.

Humans↗
PubMed2004

Language and interpersonal cognition: causal effects of variations in pronoun usage on perceptions of closeness.

Four studies examined the hypothesis that subtle language variations can have a causal impact on perceptions of relationships. In interpersonal interactions, language can function implicitly to reflect, perpetuate, and communicate relationship perceptions. Previous research has shown that interpersonal closeness and plural pronoun use are correlated; the current research demonstrates that manipulating pronoun use can lead people to perceive their own and other relationships as closer and higher in quality. In Study 1, participants who read about a relationship that was described using the pronoun we versus she and I perceived the relationship to be closer and of higher quality. Study 2 showed that pronoun variations similarly affected perceptions of participants' own ongoing relationships; Study 3 showed similar effects for perceptions of an actual interpersonal interaction. Study 4 examined potential mechanisms of this effect.

Adolescent↗
PubMed2004

The causal role of theories of relationships: consequences for satisfaction and cognitive strategies.

Two studies demonstrated the causal role of relationship theories in influencing relationship satisfaction and the processes affecting satisfaction. In both studies, participants were induced to hold either the soulmate or work-it-out theory. Feelings that one's partner was ideal (or not) were associated with relationship satisfaction more strongly for people induced to hold the soulmate theory than the work-it-out theory (Study 1). In Study 2, participants' beliefs about their relationships were threatened, and strategies for responding to this threat were assessed. Inducing people to hold the soulmate theory resulted in more relationship-enhancing cognitions if participants believed they were with the right person but more relationship-detracting cognitions if participants did not believe they were with the right person. These polarizing tendencies were enhanced under threat. In contrast, inducing people to hold a work-it-out theory produced almost no biased processing, leading people to process information similarly, regardless of their feelings about their partner.

Adolescent↗
PubMed2026

Unveiling m7G modification patterns and causal drivers governing intracranial aneurysm rupture risk through multi-omics validation and m7G-MeRIP-seq profiling.

Intracranial aneurysm (IA) rupture causes severe brain hemorrhage with high mortality, yet its molecular drivers remain unclear and better risk prediction is urgently needed. Using transcriptomics, single-cell analysis, and genetic data, we investigated the role of N7-methylguanosine (m7G) RNA modification in IA. We identified distinct m7G modification patterns, validated their methylation features in patient samples, and incorporated these patterns into a machine learning-based rupture prediction model. The presence and characteristics of m7G patterns significantly improved model performance, achieving high predictive accuracy across three independent cohorts (AUC 0.91-0.95). Genetic analyses further identified three causal m7G-related genes (NSUN2, IFIT5, SNUPN), and laboratory experiments confirmed their altered expression and methylation in ruptured aneurysms. Overall, our findings demonstrate that m7G modifications play a key role in IA rupture. The validated prediction model offers strong clinical potential for rupture risk assessment, and the identified genes represent promising therapeutic targets.

Humans↗
PubMed1990

The circadian basis of ovarian diapause regulation in Drosophila melanogaster: is the period gene causally involved in photoperiodic time measurement?

Females of a wild-type strain of Drosophila melanogaster (Canton-S), and of several clock mutants (period), were able to discriminate between diapause-inducing short days and diapause-averting long days with a well-defined critical daylength. The critical daylengths of a short-period mutant (pers) and a long-period mutant (perL2) were almost identical, both to each other and to that of Canton-S. The critical daylength of an arrhythmic mutant (perol), however, was about 3 hr shorter than that of Canton-S, and that of per- was about 5 hr shorter. Exposure of Canton-S females to Nanda-Hamner experiments, consisting of a 10-hr photophase coupled to a dark phase varying between 4 and 74 hr, showed (1) that the photoperiodic clock in D. melanogaster measures nightlength rather than daylength, and (2) that photoperiodic time measurement is somehow based on (or affected by) constituent oscillators in the circadian system. Nanda-Hamner results for the period mutants all showed similar profiles regardless of genotype, or the presence or absence of per locus DNA. These results suggest that photoperiodic induction and locomotor activity do not share a common pacemaker in D. melanogaster, and that the per gene is not causally involved in nightlength measurement by the photoperiodic clock, although flies in which the per locus is missing (per-) or defective (perol) show an altered critical value.

Animals↗
PubMed1994

A causal modeling approach to institutionalization.

A causal model of the institutionalization process is presented. Path analysis and logistic regression are performed on NHIS Longitudinal Study of Aging data. Based on initial analysis, the model is revised and re-evaluated. Convergent results support significance for four of five proposed predictors. Results are similar for men and women. Findings suggest unidentified factors are important to nursing home admission and that attention should be given to the process of decision-making that leads to admission.

Aged↗
PubMed1990

Reliability of causal indicators for nonfatal injuries.

The applicability of the ICD E code as a causal indicator of nonfatal injuries has been criticized. New codes have been developed to replace the ICD codes. We compared the coding reliability of the ICD E and place vs. the Nordic mechanism (M) and place codes. The mean accuracy (76 vs. 70%) (p less than 0.002) and the intercoder reliability (84 vs. 69%) (p less than 0.001) were better for the E than M code. The accuracy of the place codes was the same (83%). A short training improved (p less than 0.001) the accuracy of all four codes. The replacement of the E code with the M code would not improve the reliability of data on causes of injuries.

Diagnosis-Related Groups↗
PubMed2004

The birth of Emerging Themes in Epidemiology: a tale of Valerie, causality and epidemiology.

Emerging Themes in Epidemiology (ETE) is a new, online, Open Access peer-reviewed journal. The Journal is unique in that it was conceived and is managed by research degree students in epidemiology and related public health fields. The Journal's management is overseen by its Editor-in-Chief and Associate Faculty Editors, all of whom are senior members of faculty. ETE aims to encourage debate and discussion on the theoretical, methodological and practical aspects of epidemiologic research and practice. In addition, ETE is dedicated to the promotion of Open Access publication and the training of research students in the scientific publishing process. This editorial, to coincide with the launch of ETE, sets out the Journal's philosophy and aims. Epidemiology is a rich and innovative science that has much to gain from broader discussion of the causal frameworks that underpin it. ETE aims to be a major forum for such discussion.

Journal Article↗
PubMed2005

Investigating the functional role of callosal connections with dynamic causal models.

The anatomy of the corpus callosum has been described in considerable detail. Tracing studies in animals and human postmortem experiments are currently complemented by diffusion-weighted imaging, which enables noninvasive investigations of callosal connectivity to be conducted. In contrast to the wealth of anatomical data, little is known about the principles by which interhemispheric integration is mediated by callosal connections. Most importantly, we lack insights into the mechanisms that determine the functional role of callosal connections in a context-dependent fashion. These mechanisms can now be disclosed by models of effective connectivity that explain neuroimaging data from paradigms that manipulate interhemispheric interactions. In this article, we demonstrate that dynamic causal modeling (DCM), in conjunction with Bayesian model selection (BMS), is a powerful approach to disentangling the various factors that determine the functional role of callosal connections. We first review the theoretical foundations of DCM and BMS before demonstrating the application of these techniques to empirical data from a single subject.

Algorithms↗
PubMed2006

Causal relationship from exposure to chemicals in oil refining and chemical industries and malignant melanoma.

Malignant melanoma has been thought to be related mainly to exposure to the sun or radiation. A review of the scientific literature reveals many significant correlations between benzene and benzene-containing solvents in the workplace and the occurrence of malignant melanoma, particularly in sites that have never been exposed to sunlight. A comparison of positive correlations between such exposure and malignant melanoma by independent investigators and negative findings by investigators with industry affiliations reveals that this difference, at least in part, may account for the discrepant findings. Based on independent studies, it is reasonable to conclude that malignant melanoma is causally related to employment-related chemical exposures in the petroleum refining industry.

Chemical Industry↗
PubMed1976

Parathyroid hormone as a possible causal factor in osteopetrosis of the tl rat.

The possibility of parathyroid dysfunction as a causal factor in the osteopetrosis of the tl rats was explored by evaluating serum calcium (Ca) and immunoreactive parathyroid hormone (iPTH) concentrations in this strain of rats, as compared with those of phenotypically normal littermate (LM) and non-littermate (NLM) control groups. The mean serum Ca concentration in the tl rat was not significantly different from that of the NLM group, although it was less than that of the LM group. However, all Ca values were within the normal range. The mean serum iPTH concentration in the tl rats was not significantly different from those of either control group. The data indicate that the adult tl rat has adequate but not excessive PTH secretion. Therefore, osteopetrosis and its manifestations in the adult tl are not caused by an abnormality of parathyroid function.

Animals↗
PubMed2001

Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training.

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

Amenorrhea↗
PubMed1992

The causal relationship between mutations in cAMP-dependent protein kinase and the loss of adrenocorticotropin-regulated adrenocortical functions.

The Y1 adrenocortical tumor cell mutants, Kin-7 and Kin-8, harbor point mutations in the regulatory subunit (RI) of the type 1 cAMP-dependent protein kinase (cAMPdPK) that render the enzyme resistant to activation by cAMP. These mutants also are resistant to many of the regulatory effects of ACTH and cAMP. In order to examine the causal relationships between the mutations in cAMPdPK and the resistance to ACTH and cAMP, the Kin mutants were transfected with expression vectors encoding wild type subunits of cAMPdPK in order to restore cAMP-responsive protein kinase activity. The transformants then were screened for the concomitant recovery of cellular responsiveness to ACTH and cAMP. In the mutant Kin-7, cAMP-responsive protein kinase activity was recovered after transfection with an expression vector encoding wild type mouse RI. Protein kinase activity in the mutant Kin-8 remained largely cAMP-resistant after transfection with the RI expression vector but could be rendered cAMP-responsive by transfection with an expression vector encoding the wild type catalytic subunit. The recovery of cAMP-responsive protein kinase activity was accompanied by the recovery of steroidogenic and morphological responses to ACTH and cAMP, suggesting that the cAMP-dependent signaling cascade plays an obligatory role in these actions of ACTH. The growth-regulatory effects of cAMP were not reversed with the recovery of cAMP-responsive protein kinase activity, suggesting that cAMP-resistant growth regulation results from second-site, adaptive mutations either in the original Kin mutant population or in the transformants. Studies on the conversion of 22(R)-hydroxycholesterol into steroid products in parent and mutant cells indicate that the Kin mutations reduce the steroidogenic capacity of the cell as well as inhibit the hormone- and cyclic nucleotide-dependent mobilization of substrate cholesterol.

Adenylyl Cyclases↗
PubMed1995

Miasma and "social factors" in disease causality: lessons from the nineteenth century.

Conventional public health wisdom holds that the end of the nineteenth century saw a dramatic change in beliefs about what causes disease, as early convictions about the importance of broad social factors gave way to a concentration on microorganisms. I argue, however, that in both the middle and late nineteenth century nearly everyone, professionals and laypeople alike, saw disease causality in terms of precise, invisible entities, and that prevention policies were as reductionist and narrow as the available technology would allow. My argument is based on a rereading of the primary documents that other scholars have seen as supporting the idea of two distinct public health periods, and on a new interpretation of the revisionist history that questions the idea. I suggest that health policy analysts today are too vague about the meaning of "social factors" and that disease prevention policies might be better if the term was clarified.

Disease↗
PubMed1988

A shift from acute to chronic spontaneous pyelonephritis in male MM mice associated with a change in the causal micro-organisms.

Proteus mirabilis was the predominant cause of acute diabetes-associated pyelonephritis occurring spontaneously in male MM mice until they were segregated in a new environment. Thereafter Pasteurella pneumotropica and Streptococcus faecalis emerged collectively as the most common causal organisms, the pyelonephritis became more chronic and Proteus mirabilis isolates from faeces and urine produced atypical non-swarming colonies on blood agar plates. This did not account for the reduced pathogenicity of Proteus mirabilis; when MM males were returned to the original environment the pyelonephritis again became acute but was associated with the atypical type of Proteus mirabilis although the normal type was abundant in the environment. The MM mice were Caesarean-derived and cross-fostered shortly before their transfer to the second environment, which probably accounts for their changed microbial status, but the reason for the emergence of the atypical type of Proteus mirabilis is not understood. The acute nature of the male MM pyelonephritis when caused by Proteus mirabilis parallels the situation described in other animals and humans.

Acute Disease↗