Causal Link Research Articles

Delayed Wound Healing in a Young Patient with TNXB Variants and the Role of WES

After decades of quality improvement efforts, surgical site infections and abnormal wound healing remain intermittent complications in surgery. In both cases, the complication and abnormality may be superficial, restricted to the skin, or deeper within the tissue. The synthesis of connective tissue proteins, critical for structural support as part of the extracellular matrix, is under the control of multiple genes, forming a complex adaptive network. We report an unusual case of delayed and abnormal wound healing with chronic infection in a 16-year-old patient following surgery for scoliosis. Skin patch test showed that he is allergic to cobalt, a component of fixation hardware used in his surgery. He underwent evaluation by clinical genetics with whole exome sequencing (WES) which showed two (maternally and paternally inherited) variants in the TNXB ( Tenasin XB) gene. These two variants are variants of uncertain significance (VUS). TNXB encodes tenascin-XB which is an extracellular matrix glycoprotein located primarily in the basement membrane. Autosomal recessive pathogenic and likely pathogenic variants in TNXB cause TNXB-related classical-like Ehlers-Danlos Syndrome. At present, there are no causal linkages of these VUSs in TNXB to abnormal wound healing. However, as WES becomes more affordable, its use will increase and therefore it is important that we start to document such associations.

Corruption in Namibia: Examining the Nexus Between Survey-Identified Causes and Empirical Validation

This study investigates the causal relationship between the factors identified in the 2016 National Corruption Perception Survey Report and corruption levels in Namibia. By analysing data from 2000 to 2022, the Toda-Yamamoto VAR Granger causality test was employed to investigate the impact of greed, poor leadership and law enforcement, poverty (working poverty), and poor pay (compensation to employees) on corruption levels. The results revealed statistically significant causal linkages between greed, poor leadership and law enforcement, and poverty. Poor pay, however, showed no significant causal influence on corruption. These findings highlight the necessity of tackling issues such as equal income distribution, poverty, and governance inadequacies in anti-corruption initiatives. Targeted measures based on empirical evidence can effectively reduce corruption and increase transparency in governance. Additionally, conducting more recent corruption surveys in Namibia could yield up-to-date perceptions that could be adopted in similar country-specific studies elsewhere.

Using Physics-Encoded GeoAI to Improve the Physical Realism of Deep Learning′s Rainfall-Runoff Responses under Climate Change

Recent research has shown that deep learning (DL) faces physical realism challenges in predicting runoff responses under climate change, mainly due to DL’s data dependence and lack of process understanding. In this study, a physics-encoded neural network model (dNN) was developed to adress this. dNN enables a fully process-based way to training and prediction by encoding process-based modeling knowledge into the DL architecture, including the water balance principle and causal linkages of catchment hydrological processes. To examine whether dNN can produce reliable runoff responses under warming scenarios, we first conducted regional training for dNN on daily runoff in 29 catchment in California. Two process-based models, EXP-HYDRO and HBV, were then developed as benchmarks. Both dNN and a pure data-driven LSTM were forced under warming scenarios, and the monthly hydrographs and total runoff ratios metrics were evaluated relative to the benchmarks. The results demonstrated: (1) For monthly hydrographs, dNN exhibited advantages in capturing cold-season runoff increase and warm-season recession than LSTM, effectively predicting the changes and trends in monthly runoff under warming scenarios; (2) For total runoff ratios, dNN predicted fewer catchments with increased runoff, indicating it can better maintain the total water budget under warming scenarios; (3) Through the synergy with physics, dNN was able to reasonably infer unobserved snowpack dynamics under warming scenarios. These results highlight the credibility and necessity of considering physics for DL in predicting runoff responses under climate change. Overall, this study provides a promising solution for considering physics in DL to further improve the process understanding in changing environments.

Excess topography and outburst flood: Geomorphic imprint of October 2023 extreme flood event in the Teesta catchment of Eastern Himalayas

The 2023 South-Lohnak Lake outburst flood event across the upstream Teesta catchment triggered short-lived, high-magnitude flooding and substantial socioeconomic disruption downstream. We performed landscape analysis across the Teesta catchment using topographic metrics to understand the geomorphic response to this extreme flood event. We estimated the various topographic metrics such as ksn anomaly (normalized channel steepness index) (∼500–2500 m0.9), SL-index (stream-length gradient index) (∼5000–7000 m), and KsnQ (channel steepness-weighted discharge) along the trunk channel draining through the South-Lohnak Lake, which shows high magnitude in flooded regions and numerous spikes in their longitudinal profiles across mass-wasting regions downstream. We used the KsnQ metric as an event characteristic to investigate the changes in the channel morphology due to high-magnitude flooding. There was a sudden increase in the magnitude of the KsnQ metric when the river traversed through the Chungthang dam over the high ranges of excess topography (∼0–1700 m). This shows that the downstream channel morphology changes rapidly during this flood event, and KsnQ is a significant indicator of geomorphic change. To understand the spatial relationship between the physical drivers that trigger this outburst flood, we quantified the causal relationship between glacial-hydrological drivers over the upstream Zemu-sub catchment. Our observations suggest that precipitation intensity and surface temperature had a significant direct causal influence on snowmelt and snow depth (in terms of water equivalent) over the event duration with a 5-day and 1-day lag composite. Through the inclusion of lagged composites and causal linkages, the drivers across the glaciated landscape serve as event anomalies, which trigger the glacier hillslope failure and subsequent high-magnitude outburst flooding. Therefore, we suggest that the interaction of topographic discontinuity with hydrological extremes and their causal interdependencies influences this outburst event in the upper reaches, followed by high-magnitude flooding in the downstream reaches of the Teesta River. However, the long-term geomorphic consequences of such events on the evolution of the regional landscape remain unclear.

Doctors only blame the patients: a systems analysis of polycystic ovarian syndrome (PCOS)

PurposeThis study is conducted to understand an emerging public health problem in the garb of polycystic ovarian syndrome (PCOS) that affects about 6–21% of women in reproductive age from a systems perspective.Design/methodology/approachThe research is conducted in two phases. In phase 1, 15 women suffering from PCOS were interviewed to generate a knowledge map using an interpretive phenomenological research approach. The emerging themes were divided into four categories, namely individual, familial, societal, organizational, medical and systemic. In phase 2, five workshops were conducted with six invited actors to generate a causal loop diagram (CLD) of PCOS. The Standards for Reporting Qualitative Research (SRQR) are used in this study.FindingsA CLD from an individual's perspective with implications on organizational, societal and system levels.Research limitations/implicationsAwareness of “lifestyle diseases” is increasing, and this research shall help future studies put PCOS in the larger psychosocial context. The geographical location of respondents can be a limitation, as the causal linkages could only be true for the research site.Practical implicationsThe CLD provides a comprehensive understanding of complex emerging phenomenon of PCOS.Social implicationsThe paper draws attention to factors such as frequently changing doctors, withdrawal from work, medication fatigue, inclination to adopt due to infertility, etc.Originality/valueThis is the first such paper laying out the causal relationships between factors at the individual levels and connecting them to societal, organizational and system levels. This mapping can be useful for policymakers and industry leaders to empathize with PCOS sufferers so that their working conditions can be managed better.

Employee green innovation behavior based on the ability-motivation-opportunity framework: fuzzy-set qualitative comparative analysis

PurposeThe increasing emphasis on ecological responsibility within Chinese enterprises has underscored the critical role of employees’ green innovation behavior in enhancing environmental performance and enhancing core competitiveness. Grounded in the Ability, Motivation, and Opportunity (AMO) theoretical framework, this study employs configuration analysis to investigate the driving mechanisms behind the multi-factorial interplay affecting employees’ green innovation behaviors.MethodologyData was collected through questionnaires distributed among a random sample of 219 Chinese corporate employees. fuzzy-set Qualitative Comparative Analysis (fs-QCA) was then applied to identify the specific configurations contributing to high levels of green innovation behavior.Findings(1) There are three driving paths for employees’ green innovation behaviors: a leadership-organization co-driving path composed of green self-efficacy, environmentally transformative leadership, and organizational support; a leadership-driving path composed of green self-efficacy, environmentally transformative leadership, internal motivation, and external motivation; and an organization-driving path composed of green self-efficacy, organizational support, internal motivation, and external motivation. (2) There are three non-green innovation behavior-driven paths: they are divided into organizational support lack type, leadership-organizational joint lack type, and capability lack type. (3) Under specific conditions, motivational factors and environmental change leadership, motivational factors and sense of organizational support can promote employees’ green innovation through equivalent substitution.Originality(1) Significant emphasis is placed on examining how Ability, Motivation, and Opportunity synergize to shape employees’ green innovation behaviors, addressing a gap in the literature regarding their collective influence. (2) The study applies a configural approach to unravel the complex causal linkages influencing employees’ green innovation behaviors, offering detailed insights into the dynamics between individual attributes and contextual factors. (3) This research elucidates the combined effects of factors such as organizational support, leadership styles, and employees’ intrinsic and extrinsic motivations, and how they collaborate to foster an environment conducive to green innovation.ImplicationsThe findings not only enrich the theoretical understanding of green innovation behavior but also provide strategic recommendations for Chinese enterprises to encourage such behavior. These insights are essential for guiding sustainable development and enhancing competitive advantage.

The impact of innovative leadership and total quality management in 21st-century banking: an empirical insight and foresight

Purpose The purpose of this paper is to examine how innovative leadership (INL) drives innovation performance (INP) in banks. Design/methodology/approach This study develops and investigates a research model by assessing the viewpoints of 260 chief executive officers (CEOs) from the branches of 21 quality-certified banks, leveraging the Smart partial least squares technique. Findings INL had a positive and significant impact on INP. Total quality management (TQM) partially and significantly mediated the association between INL and INP. Technological turbulence, government regulation (GOV), market dynamism (MKD) and industry competitiveness (CMP) positively and significantly moderated the INL–TQM association. Research limitations/implications INP causal linkages and variations may be better understood with longitudinal investigations, hence the need for further studies in this area. External influences may affect industries or contexts differently, requiring further research into various industries. Practical implications In an industry with fast-paced and ever-changing industrial technology, strict government laws, a higher level of MKD and increased competition, firms must hire or groom innovative CEOs to promote the adoption of new and creative quality enhancement strategies that meet clients’ short- and long-term needs. Originality/value To the best of the authors’ knowledge, this paper is the first to show how TQM can serve as a pathway for innovative leaders to follow. It is an inaugural attempt to explain the specific environmental dynamics that are necessary for the INL–TQM association to thrive.

Exploring the causal relationships between cholelithiasis, cholecystitis, cholecystectomy, and gastroesophageal reflux disease: A bidirectional two-sample mendelian randomization study.

Biliary disorders and gastroesophageal reflux disease (GERD) frequently coexist. However, precise linkages between these conditions remain to be clarified. Univariable Mendelian randomization (MR), Bayesian weighted MR (BWMR) along with multivariable MR approaches were conducted using genetic instruments to evaluate the causality involving biliary disorders and GERD. Furthermore, an investigation was conducted on the potential mediating roles of biliary disorders (or GERD), on the linkage involving body mass index (BMI) and GERD (or biliary disorders). Univariable MR analyses revealed significant causal effects of genetically predicted cholelithiasis (odds ratio (OR)=1.04, P=0.0001), cholecystitis (OR=1.06, P=0.0004), and cholecystectomy (OR=2.56, P=1.05×10-6) on GERD. These findings were replicated in the FinnGen cohort and were also confirmed by BWMR and multivariable MR analyses. Additionally, mediation analyses demonstrated that cholelithiasis and cholecystitis acted as partial mediators, linking BMI causally to GERD. Conversely, GERD exhibited causal effect on cholelithiasis (OR=1.52, P=9.17×10-30) and cholecystitis (OR=1.90, P=3.32×10-28), which remained significant after BWMR and multivariable MR analyses. Mediation analyses further revealed significant mediating effect of GERD on how BMI influenced cholelithiasis/cholecystitis. Our study elucidates the bidirectional causal linkages involving cholelithiasis, cholecystitis, cholecystectomy, and GERD. These results highlight the significance of GERD risk assessment in individuals suffering from biliary diseases and vice versa.

Spatial regulation of substrate adhesion directs fibroblast morphotype and phenotype.

The switching of the fibroblast phenotype to myofibroblast is a hallmark of a wide variety of tissue pathologies. This phenotypical switch is known to be influenced not only by humoral factors such as TGF-β, but also by mechanical and physical cues in the cellular environment, and is accompanied by distinctive changes in cell morphology. However, the causative link between these cues, the concomitant morphological changes, and the resulting phenotypic switch remain elusive. Here, we use protein micropatterning to spatially control dermal fibroblast adhesion without invoking exogenous mechanical changes and demonstrate that varying the spatial configuration of focal adhesions (FAs) is sufficient to direct fibroblast phenotype. We further developed an automated morphometry analysis pipeline, which revealed FA eccentricity as the primary determinant of cell-state positioning along the spectrum of fibroblast phenotype. Moreover, linear fibronectin patterns that constrain the FAs were found to promote a further phenotype transition, characterized by dispersed expression of alpha-smooth muscle actin, pointing to an interesting possibility of controlling fibroblast phenotype beyond the canonical fibroblast-myofibroblast axis. Together, our study reveals that the spatial configuration of adhesion to the cellular microenvironment is a key factor governing fibroblast morphotype and phenotype, shedding new light on fibroblast phenotype regulation.

Combining Mendelian Randomization Analysis and 3D-QSAR to Investigate the Effectiveness of a New Series of Hydroxyquinolines in Osteoarthritis.

Osteoarthritis (OA) represents a persistent degenerative joint ailment. As OA advances, profound joint pain coupled with diminished joint function inflicts substantial physical distress and psychological strain on patients. Presently, pharmacological solutions for arthritis remain limited, primarily encompassing analgesics and joint replacement surgical procedures. Hence, non-operative strategies to mitigate osteoarthritis progression have captured significant attention in orthopedic research. This study aims to discern a definitive causal linkage between ADAMTS-4/5 and osteoarthritis through Mendelian randomization analysis. Moreover, it seeks to anticipate the therapeutic efficacy of a suite of emergent hydroxyquinolines for osteoarthritis using the Quantitative Structure-Activity Relationship (QSAR) methodology. Within this study, genetic variants specific to knee osteoarthritis were procured as exposure variables from a genome-wide association study (GWAS). Genetic variant data for ADAMTS-4/5 served as the endpoint to evaluate the causal nexus employing univariate Mendelian randomization. This analysis underpins the hypothesis that ADAMTS-4/5 presents a promising therapeutic target for osteoarthritis management. The suppressive properties of novel hydroxyquinolines against ADAMTS-4/5 were subsequently examined through conformational analyses, underscoring the potential of these compounds as therapeutic candidates for osteoarthritis. IVW outcomes from the Mendelian randomization revealed a significant association of KOA (OR: 1.1675, 95% CI: 1.0003-1.3627, P = 0.0495) with ADAMTS-5. However, KOA (OR: 1.0801, 95% CI: 0.9256-1.2604, P = 0.3278) displayed no evident connection with ADAMTS-4. Notably, the instrumental variables manifested neither heterogeneity nor horizontal pleiotropy. In this research endeavor, 16 pharmacological models were formulated via the CoMSIA method within 3D conformational relationship evaluations. A synergistic interplay of hydrophobic, spatial, and hydrogen-bonded receptor domains emerged as the most predictively potent. The cross-validation coefficient q2 for the optimum model stood at 0.716, with a principal component score of 5, a regression coefficient r2 of 0.971, a standard estimation error of 0.351, and an f-value of 156.951. Such metrics intimate the commendable predictive prowess of our devised CoMSIA models. The research unearthed a robust causal interrelation between ADAMTS-5 and osteoarthritis via Mendelian randomization. Furthermore, a credible drug model targeting ADAMTS-5 was constructed. Collectively, these findings illuminate a path forward in the pursuit of target-specific drugs for osteoarthritis management in subsequent investigations.

Phenotypic Heterogeneity in Pathogens.

Pathogen diversity within an infected organism has traditionally been explored through the lens of genetic heterogeneity. Hallmark studies have characterized how genetic diversity within pathogen subpopulations contributes to treatment escape and infectious disease progression. However, recent studies have begun to reveal the mechanisms by which phenotypic heterogeneity is established within genetically identical populations of invading pathogens. Furthermore, exciting new work highlights how these phenotypically heterogeneous subpopulations contribute to a pathogen population better equipped to handle the complex and fluctuating environment of a host organism. In this review, we focus on how bacterial pathogens, including Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, and Mycobacterium tuberculosis, establish and maintain phenotypic heterogeneity, and we explore recent work demonstrating causative links between this heterogeneity and infection outcome.

Radiation-Induced Lymphopenia is a Causal Mediator of Survival After Chemoradiation Therapy for Esophagus Cancer

Purpose: Radiation-induced lymphopenia (RIL) is common during chemoradiotherapy. Severe lymphopenia is associated with reduced survival. Proton beam therapy (PBT), with its substantially more compact dose distributions, spares circulating lymphocytes and immuno-organs at risk to a greater extent than does photon therapy. Recent studies comparing PBT to photon radiotherapy, specifically intensity-modulated radiation therapy (IMRT), for esophageal cancer (EC) showed that the incidence of grade 4 RIL (G4RIL) is significantly reduced among patients receiving PBT for esophageal cancer. However, whether the extent of this reduction has a direct causative link with improved survival is unknown. This study applies causal mediation analysis to answer this question. Methods and Materials: We retrospectively assessed 734 patients treated with concurrent chemoradiotherapy for biopsy-proven EC from 2004 through 2017. To address the potential for bias in the choice of radiation modality, propensity score analysis was used to evaluate and reduce imbalances between the PBT and IMRT cohorts. Causal mediation analysis was applied to decompose the total effect of radiation modality on overall survival (OS) into indirect (mediated through G4RIL) and direct effects. Results: We found that PBT was associated with significantly lower incidence of G4RIL and prolonged OS compared with IMRT (odds ratio [OR]= 0.41, 95% confidence interval [CI] 0.28 to 0.60, P<0.001). In the propensity-matched cohort of 506 patients (253 PBT, 253 IMRT), G4RIL risk reduction with PBT vs. IMRT translated into a 5% reduction in the relative rate of death (P=0.032). Mediation of G4RIL explained ∼14.5% of the difference in OS. Conclusions: G4RIL was found to mediate survival; however, statistically significant direct effect of PBT on survival was not observed. In other words, the survival benefit from protons over photons in this EC cohort was lost in the absence of G4RIL risk reduction.

Does Aid Induce Foreign Direct Investment: Updated Evidence from a Quasi-Experiment

Abstract While the catalytic effect of aid on foreign direct investment (FDI) has long been an implicit consensus among many policymakers and practitioners, assessments of this causal relationship remain limited and are not always reliable. To mitigate this evidence gap, this study applies an instrumental variable approach that leverages the graduation of the International Development Association (IDA) income threshold as a quasi-experiment to identify the causal linkage between foreign aid and FDI. The analysis reveals that a 1 percent drop in the ratio of aid to gross national income leads to a decline in FDI relative to gross domestic product by 0.9 percent in 42 developing countries from 1987 to 2019. In face of the aid shock induced by IDA graduation, governments in recipient countries restrict their financial policy openness, through which aid could significantly impact subsequent foreign private investment. Results emphasize the necessity of concerted policy interventions to mitigate this negative aid shock.

How do climate policy uncertainty and renewable energy and clean technology stock prices co-move? evidence from Canada

AbstractThis work probes the dynamic co-movement between the Climate Policy Uncertainty Index (CPU) and the Renewable Energy and Clean Technology Index (RECT) employing the novel wavelet power spectrum (WPS) and wavelet coherence (WC) approaches for monthly data between 2013 and 2022. Using the wavelet approach enables us to observe the causality direction from both time and frequency dimensions and also to help detect the causal linkage in the short-medium and long-term horizons. This is the first study aiming to perform this relationship from both time and frequency dimensions. Remarkably, findings reveal that: i) CPU seems only volatile in 2019 and 2021 in the short run; (ii) there was significant volatility in the RECT in the short and long terms (SLT) between 2018 and 2022; (iii) RECT significantly caused the CPU between 2014 and 2018; iv) after 2019, CPU started to cause RECT in the short and medium terms (SMT).

The web of conflict-related interactions in Colombia: exploring causal linkages between ecological and social variables by the qualitative loop analysis.

In Colombia, the long-lasting internal conflict heavily shaped the socio-ecological context and imposed relationships that persisted after the peace agreement was signed in 2016. One question of interest is whether policies or interventions conceived to attain desirable goals for the post-conflict society may be effective or, rather, if the constraints imposed by the conflict scenario might produce unintended effects, either on the environmental or the social side. To explore this issue, we envisaged the socio-ecological system as a parsimonious set of characteristic ecological and social variables within the conflict-related framework and reconstructed their interactions, exploiting elicitation-based information and the literature. We visualized the resulting interactive networks as signed digraphs. Applying the qualitative technique of loop analysis combined with numerical simulations, we predicted the response of the system to policies as drivers of change, such as subsidized credit to capital-intensive activities or policies that increase small farming competitiveness and access to markets. Highlighting causal linkages reveals that the persistence of conflict factors may produce unexpected interdependencies between licit and illicit activities and that, only in a few cases, the persistence of these mechanisms allows synergies between desirable goals.This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

The causal relationship between autoimmune diseases and rhinosinusitis, and the mediating role of inflammatory proteins: a Mendelian randomization study.

Observational studies have linked autoimmune diseases (ADs) with rhinosinusitis (RS) manifestations. To establish a causal relationship between ADs and RS, and to explore the potential mediating role of inflammatory mediators between ADs and RS, we utilized Mendelian randomization (MR) analysis. Using a two-sample MR methodology, we examined the causality between multiple sclerosis (MS), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), type 1 diabetes (T1D), Sjogren's syndrome (SS), celiac disease (CeD), Crohn's disease (CD), hypothyroidism (HT), Graves' disease (GD), and Hashimoto's thyroiditis and their association with chronic and acute rhinosinusitis (CRS and ARS, respectively).To achieve this, we employed three distinct MR techniques: inverse variance weighting (IVW), MR-Egger, and the weighted median method. Our analysis also included a variety of sensitivity assessments, such as Cochran's Q test, leave-one-out analysis, MR-Egger intercept, and MR-PRESSO, to ensure the robustness of our findings. Additionally, the study explored the role of inflammation proteins as a mediator in these relationships through a comprehensive two-step MR analysis. Among the ADs, MS, RA, T1D, CeD, and HT were determined as risk factors for CRS. Only CeD exhibited a causal relationship with ARS. Subsequent analyses identified interleukin-10 (IL-10) as a potential mediator for the association of MS, RA and HT with CRS, respectively., while C-X-C motif chemokine 10 levels (CXCL10) and T-cell surface glycoprotein CD6 isoform levels (CD6) were found to influence HT's effect on CRS. Our findings demonstrate a causative link between specific autoimmune diseases and rhinosinusitis, highlighting IL-10, CXCL10, and CD6 as potential mediators in this association.

Towards a Biologically Coherent Account of the Brain and How It Develops

Different conceptualizations of brain function have different implications for understanding the relation of neuroscience to the study of human development. In one view, the brain is an isolated computational device that passively processes stimuli delivered from an external world and then mediates a response. An alternative view, which is more consistent with the evolutionary history of brains, moves away from simple causal linkages between stimulus and response and instead emphasizes the inherent, ongoing activity of the individual. Here the individual is not directly instructed by information from its environment but instead shapes its own sensory inputs through its goal-directed activity. Related conceptual confusions around instructions and information can be found in accounts of brain development that either fall back on a genetic blueprint or that elevate the role of extrinsic experience. A more coherent approach brings together aspects of developmental and evolutionary biology while drawing on developmental systems theory and particular themes in embodied cognitive science. Such an approach spans qualitatively different frames of explanation across a range of spatiotemporal scales, necessitating a reconsideration of disciplinary boundaries. Fully engaging in this effort can yield a more integrative science of brain, mind, and behavior and an enriched understanding of human development.

The causal relationship of depression, anxiety, and neuroticism with endometriosis: A bidirectional 2-sample Mendelian randomization study.

Endometriosis, identified by the abnormal growth of endometrial cells beyond the inner lining of the uterus, often manifests through symptoms like painful menstruation and challenges in conceiving. Observational studies suggest that endometriosis is often comorbid with mental disorders, including anxiety and depression. The nature of these connections, whether they are causal, is still debated and calls for further empirical evidence. We utilized a bidirectional 2-sample Mendelian randomization (MR) approach, harnessing genome-wide association study data to explore the connections among depression, anxiety, neuroticism, and endometriosis. To scrutinize the causative connections between mental health issues and endometriosis, Inverse Variance Weighting (IVW) was employed as the primary analytical tool, complemented by Weighted Median Estimation, Simple mode, Weighted mode, and MR-Egger regression for additional analysis. To examine the potential for reverse causation, reverse MR was applied. To strengthen the reliability of our findings, we carried out sensitivity analyses that included heterogeneity tests, tests for pleiotropy, and leave-one-out analyses. The IVW analysis revealed a significant correlation between the genetic inclination towards depression and a heightened risk of developing endometriosis [Odds Ratio (OR) = 1.151, 95% Confidence Interval (CI) = 1.025-1.293, P = .017]. Similarly, a genetic predisposition to neuroticism was significantly associated with an increased risk of endometriosis (OR = 1.128, 95% CI = 1.038-1.226, P = .004). However, no causative link was found between genetic susceptibility to anxiety and the occurrence of endometriosis. Reverse MR analysis did not support a bidirectional genetic susceptibility between endometriosis and psychiatric disorders. The MR analysis presents genetic data supporting the notion that depression and neuroticism are risk factors for endometriosis. Conversely, it found no evidence of a causal connection between anxiety and the development of endometriosis. Enhancing mental health treatment should be considered a preventive measure against endometriosis.

Inflammatory factors and the risk of urolithiasis: a bidirectional Mendelian randomization study.

Urolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive. Mendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis. Our study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-β) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1β) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (β = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (β = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (β = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (β = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (β = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (β = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (β = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (β = 0.126, 95% CI = 0.044-0.208) levels. These discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-β and MIP-1β influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.

Causal inference reveals the dominant role of interannual variability of carbon sinks in complicated environmental-terrestrial ecosystems

Climate factors (CFs) are key variables shaping the interannual variability (IAV) of terrestrial ecosystem carbon sinks. However, the dominant CFs influencing the IAV of terrestrial carbon sinks remains debated, as CFs are coupled via land-atmosphere interactions. Here, the dominant factors influencing the IAV of global terrestrial net ecosystem production (NEP) were quantified using the convergent cross-mapping (CCM) technique. This analysis was conducted with distinct global terrestrial NEP datasets deriving from process-based ecosystem models, machine learning techniques, and eddy covariance flux towers. Results revealed that the spatial patterns of IAV of global terrestrial NEP were dominated by water availability (WA) and temperature (Ts). Ts mainly controlled the IAV of terrestrial NEP in mid to high-latitude regions of the Northern Hemisphere (NH), while WA exerted dominance over low and mid-latitude regions in both the NH and the Southern Hemisphere. Moreover, the energy limitation and water limitation explained the spatial pattern of Ts and WA dominant on NEP. Further analysis found that WA and Ts also played a dominant role in gross primary productivity (GPP) and terrestrial ecosystem respiration (TER), proving that WA and Ts were the dominant factors affecting NEP. In addition, we found a weakening trend in causal linkages of CFs to NEP in the temporal domain. This study used causal analysis to reveal the spatial patterns of water and heat dominating the NEP, providing support for improved assessment and prediction of terrestrial carbon sinks under climate change.