Search Results (112)

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article

Money laundering poses a serious threat to financial stability and requires effective national frameworks for prevention. This study investigates how the quality of legal and institutional frameworks affects the effectiveness of national anti-money laundering (AML) systems and their implications for financial risk management. We conducted an empirical analysis of 132 jurisdictions in 2024 using the Basel AML Index (AMLI) and the WJP Rule of Law Index (RLI). The Random Forest method was employed to model the relationship between rule-of-law indicators and AML risk levels. Findings reveal a significant inverse relationship between rule-of-law indicators and AML risk levels, with an overall classification accuracy of 69.6%. The model performed best for low-risk countries (precision 75%, recall 92.31%), moderately for medium-risk countries (precision 65.22%, recall 78.95%), but failed to identify high-risk jurisdictions, suggesting a legal institutional “threshold” necessary for effective AML functioning. Key predictors included protection of fundamental rights and mechanisms for civil oversight, with strong negative correlations between AML risk and criminal justice impartiality (−0.35), civil justice fairness (−0.35), and equality before the law (−0.41). These results show that legal factors strongly affect AML risk and can guide regulators in improving risk-based standards, enhancing regulatory certainty, and managing financial risk. Full article

Background: Brain-derived neurotrophic factor (BDNF) is a key regulator of neuroplasticity, cognitive function, and mental health. Exercise is proposed as a non-pharmacological strategy to enhance BDNF; however, findings across neurological and non-neurological disorders remain inconsistent, and the influence of exercise type or dose-related parameters remains unclear. Objective: This meta-analysis evaluated the effects of exercise interventions on peripheral BDNF levels in individuals with neurological (e.g., multiple sclerosis, cognitive impairment, schizophrenia, depression) and non-neurological (e.g., obesity, type 2 diabetes, cancer) disorders, and examined whether outcomes varied by disease category, exercise modality, or dose. Methods: A systematic search of Web of Science, PubMed, ScienceDirect, Scopus, and Cochrane was conducted up to 1 October 2025. Eligible randomized controlled trials (RCTs) and the quality of evidence were assessed using the PEDro scale and the GRADE approach, respectively. Random-effects models were applied, with subgroup analyses (neurological vs. non-neurological; exercise type; duration and assay type), meta-regressions (duration, frequency, session length), and publication bias tests (funnel plot, Begg’s test, Egger’s regression, and trim-and-fill). Results: Nineteen RCTs, including 850 participants, were analyzed. According to low-quality evidence, exercise significantly increased peripheral BDNF (SMD = 1.03, 95% CI: [0.56–1.49, p < 0.0001). Effects did not differ significantly between neurological (SMD = 0.91, 95% CI: 0.31–1.50) and non-neurological (SMD = 1.23, 95% CI: 0.47–1.99) conditions (Q (1) = 0.44, p = 0.51). Subgroup analyses revealed significant improvements for resistance exercise (SMD = 1.57, 95% CI: 0.91–2.23), followed by aerobic (SMD = 1.44, 95% CI: 0.36–2.52) and combined exercise (SMD = 0.55, 95% CI: 0.21–0.89). Meta-regressions showed no moderating effects of duration (β = 0.0101, p = 0.834), weekly frequency (β = 0.1464, p = 0.648), minutes per session (β = −0.0124, p = 0.233) or total weekly minutes (β = 0.0005, p = 0.919) apart from age and baseline BDNF level factors (β = 0.0348, p = 0.020; β = −0.035, p = 0.0258). Publication bias tests indicated minimal publication bias, with adjusted effects remaining robust. Conclusions: Exercise interventions have been shown to increase peripheral BDNF significantly across diverse clinical populations. In particular, resistance and aerobic exercise protocols accounted for the exploratory component, whereas simple dose-related factors did not explain the variability. These findings are consistent with the biological plausibility of exercise-induced neuroplasticity and underscore the need for larger, pre-registered RCTs with harmonized biomarker protocols to strengthen clinical translation. However, the certainty of evidence is limited by small sample sizes and the frequent lack of blinding of participants and assessors across included trials. Full article

Aims: Recommendations for cancer survivors concur regarding physical activity (PA), and elucidating factors governing PA uptake among colorectal cancer (CRC) survivors is needed. This study examined the impact of PA interventions and investigated the variation in PA across several characteristics, including race/ethnicity. Design: We performed a systematic review and aggregate data meta-analysis of randomized controlled trials (RCTs) of PA interventions. Data Sources: We used studies from CENTRAL, PubMed (NCBI), PsycINFO (EBSCOhost), CINAHL (EBSCOhost) with full text, Scopus (ELSEVIER), and the Web of Science (CLARIVATE) (1 May 1993–1 September 2023). Methods: For the meta-analysis, the inverse variance heterogeneity (IVhet) model was used to pool standardized mean difference effect sizes (Hedge’s g) for our primary outcome, changes in PA. Results: Sixteen studies representing 1668 participants were included in the meta-analysis. A moderate, statistically significant increase in PA was observed (g = 0.44, 95% CI 0.12–0.76; p = 0.01). However, a large amount of inconsistency was observed (I² = 80.8%, 95% CI, 36.1% to 90.9%), as well as major asymmetry suggestive of small-study effects (publication bias, LFK = 3.04). Only 28% of trials reported race/ethnicity, limiting equity analyses. Subgroups comparing atheoretical vs. theory-based interventions did not differ statistically. Meta-regression results suggested associations with specific behavior change theories and delivery features. Based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment, the overall certainty of evidence was considered low. Conclusions: There is low-certainty evidence that PA interventions may improve PA among CRC survivors. Future trials should (i) recruit and report diverse samples in a clear and transparent manner, (ii) explicitly map theory constructs to techniques and test mechanisms, and (iii) report fidelity and clinically meaningful thresholds alongside behavioral outcomes. Full article

The occurrence of mountainous geological hazards, primarily including rockfalls, landslides, and debris flows, is frequently influenced by multiple environmental factors and exhibits significant spatial heterogeneity and cumulative effects. To address the need for regional-scale susceptibility assessments within complex geological settings, we propose a novel geological hazard susceptibility assessment model based on conditional probability. This study establishes a dual-module evaluation framework incorporating certainty factors (CFs) and weights (W), in which the CF quantifies the contribution of each factor class to hazard occurrence, while the weights reflect the relative importance of the conditioning factors, thereby improving the model’s capability to characterize multifactorial coupling effects. Using three representative mountainous regions in Xinjiang, China—the Ili Valley Region (IVR), the Northern Piedmont of the Tianshan Mountains (NPTM), and the Kunlun–Altun Mountain Region (KAMR)—we integrate 7938 historical hazard points and 11 conditioning factors within a GIS environment to conduct the assessment. The results reveal regional differences in the weights of conditioning factors: IVR is primarily controlled by Elevation (0.184), Urban-Critical Infrastructure Density (0.163), and Annual Precipitation (0.156); NPTM is dominated by Annual Precipitation (0.153), Urban-Critical Infrastructure Density (0.145), and Road Density (0.136); and KAMR is governed by Elevation (0.197), Seismic Acceleration (0.167), and Hydrogeological Type (0.134). In IVR, NPTM, and KAMR, the Very-High and High susceptibility zones occupy 37.10%, 34.86%, and 26.23% of the land area, respectively, and contain 78.18%, 77.24%, and 82.10% of the identified geological hazards. The region-specific ROC-AUCs are 0.8536 (IVR), 0.8545 (NPTM), and 0.8775 (KAMR), indicating good predictive capability across sedimentary basins and tectonically active zones. This study provides methodological and data support for quantitative risk assessment of geological hazards at the regional scale under complex geological conditions. Full article

Background: We evaluated certain factors relative to onion (Allium spp.) and onion-derived polyphenols. Methods: We searched PubMed, Scopus, and Google Scholar from 2010 to 20 October 2025 without language limits. Eligible designs comprised of in vitro, animal, and human studies assessing onion, onion extracts, or isolated onion-derived polyphenols with bone outcomes. Two reviewers independently screened, extracted, and assessed risk of bias (RoB 2 for RCTs; SYRCLE for animals). Results: We included X studies (a in vitro, b animal, and c human RCTs; N samples). In vitro limitations included the following: heterogeneous models, short human follow-up, small samples, and moderate-to-serious risk of bias in animals. Reports included improvements in bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and osteoclast/osteoblast activity. Onion extracts consistently inhibited RANKL-induced osteoclastogenesis while sparing osteoblast function. In animals, onion or quercetin/kaempferol preserved BMD and improved mineral content and (in several models) fracture healing. In one small RCT of onion juice (8 weeks), antioxidant status improved with a trend to attenuated BMD loss; a resveratrol RCT was excluded/included as a benchmark. Conclusions: Pre-clinical evidence suggests anti-resorptive and osteogenic effects of onion-derived polyphenols; human evidence is limited and characterized by low certainty. Longer RCTs are needed to define effective doses and clinical relevance. Full article

Objectives: This systematic review and meta-analysis evaluated differences in job satisfaction scores between nurses and physicians, examining variation by (a) care setting (hospital, emergency department, outpatient, mixed), and (b) time period (pre-COVID, during COVID, post-COVID). Methods: We systematically searched PubMed, Scopus, ScienceDirect, Web of Science, and CINAHL for studies published between January 2020 and July 2025. Eligible studies reported mean and standard deviation values for job satisfaction among physicians and nurses in healthcare settings across the specified timeframes. Studies were excluded if they assessed other types of satisfaction or combined data across COVID periods. Pooled standardized mean difference (SMD) was calculated using random-effects models in R. Results: Before COVID-19, the SMD was −2.40 (95% CI −8.05 to 3.26; I² = 98%). During the pandemic, the estimate was 1.39 (95% CI −0.57 to 3.35; I² = 91.5%), and post-pandemic, it remained small (SMD = 0.29; 95% CI −1.63 to 2.22; I² = 95.8%). Emergency care during COVID showed a significant advantage for physicians (SMD = 0.29; 95% CI 0.05 to 0.52; I² = 0%). Post-COVID, mixed settings slightly favored physicians (SMD = 0.06), while primary care favored nurses (SMD = −0.30); subgroup differences were significant. Conclusions: The findings reveal that job satisfaction is not solely determined by professional role but is significantly influenced by temporal and contextual factors. Job satisfaction is shaped more by temporal and contextual factors than by professional role. While no consistent differences were observed pre-pandemic, emergency care favored physicians during COVID, and post-pandemic trends showed modest advantages for nurses in primary care and physicians in mixed settings. Due to the methodological limitations of this meta-analysis, including high heterogeneity, reliance on cross-sectional data, and very low/low certainty of evidence, these results should be interpreted with caution. Full article

The southwestern region of China is highly susceptible to landslides due to steep terrain, fractured geology, and intense rainfall. This study focuses on the Xiluodu Reservoir area in Yunnan Province and applies Geographic Information System (GIS) techniques together with ten key spatial factors—such as slope, lithology, elevation, and distance to rivers—to perform a quantitative landslide risk assessment. In addition to the individual Certainty Factor (CF) and Logistic Regression (LR) models, we developed an integrated CF–LR coupled model to overcome their respective limitations: the CF model’s sensitivity to specific factor attributes but neglect of factor interactions, and the LR model’s robust weight estimation but weak representation of attribute heterogeneity. By combining these strengths, the CF–LR model achieved superior predictive performance (AUC = 0.804), successfully capturing 92.5% of historical landslide events within moderate-to-high risk zones. The results show that lithology, slope angle, and proximity to rivers and roads are dominant controls on susceptibility, with landslides concentrated on soft rock slopes of 30–40° and within 600–900 m of rivers. Compared with previous coupled approaches in similar mountainous reservoir settings, our CF–LR model provides a more balanced and interpretable framework, enhancing both classification accuracy and practical applicability. These findings demonstrate that GIS-based CF–LR integration is a novel and reliable tool for landslide susceptibility mapping, offering important technical support for disaster prevention and risk management in large reservoir regions. Full article

Community-based tourism (CBT) is deemed a powerful means for enhancing community well-being and ethnic cultural preservation (CP). However, its sustainability has been challenged by resource scarcity, environmental pollution and funding instability in Vietnam. This study investigates young tourists’ perceptions of and financial contributions to community-based tourism associated with cultural preservation (CBT-CP) at Lac Village, a key White Thai ethnic site in Phu Tho province. Specifically, the contingent valuation method (CVM) coupled with an interval regression model was used to analyze the data obtained from 275 respondents during December 2024 to estimate the willingness to pay (WTP) for CBT-CP and identify influencing factors. We found that nearly 50% of the respondents are willing to contribute financially, with an average of roughly USD 4.45 per visit. This leads to total contributions of USD 2413 for all respondents and USD 1541 for respondents with a high certainty level of commitment. Additionally, we found that key barriers to WTP for CBT-CP are fiscal transparency concerns, personal financial limitations, and individual determinants. These findings offer many policy implications for mobilizing young tourists’ untapped funding, strengthening local management capacity, and advocating for enhanced transparency to improve CBT-CP in the study area and beyond. Full article

Ischemic stroke is a leading cause of disability worldwide, often triggered by atherothrombotic or embolic events. A growing body of evidence highlights the role of neuroinflammation as a central mechanism in post-stroke damage, influenced by modifiable systemic risk factors. Emerging evidence suggests that oxidative stress mediates the impact of several modifiable risk factors by activating redox-sensitive pathways (such as NF-κB), impairing nitric oxide bioavailability, and promoting matrix metalloproteinase activity that disrupts vascular integrity and contributes to ischemic injury. In this context, our meta-analysis examined major modifiable risk factors for ischemic stroke, with a particular focus on their shared ability to promote oxidative stress and neuroinflammatory cascades. By emphasizing these redox-dependent mechanisms, our work supports the biological plausibility of exploring antioxidant strategies as complementary approaches to mitigate stroke risk. Hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, and transient ischemic attacks all contribute to oxidative damage through mechanisms such as endothelial dysfunction, vascular inflammation, and excessive free radical exposure. We searched PubMed, PubMed Central, Web of Science, and Scopus for observational studies published within the last five years, identifying 23 studies (691,524 participants) meeting eligibility criteria. Using a random-effects model, we found significant associations between stroke risk and hypertension (OR = 1.58, 95% CI: 1.28–1.94), smoking (OR = 1.61, 95% CI: 1.13–2.28), type 2 diabetes (OR = 1.53, 95% CI: 1.29–1.81), atrial fibrillation (OR = 1.88, 95% CI: 1.28–2.75), and prior transient ischemic attack (OR = 1.62, 95% CI: 1.24–2.11). These risk factors are known to contribute to systemic inflammation, potentially exacerbating neuroinflammatory cascades post-stroke. Despite limitations such as heterogeneity and low certainty of evidence, our findings reinforce the relevance of targeting inflammation-driven risk factors in stroke prevention strategies and future research. Full article

Background/Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and dementia. The comparative prognostic value of MRI-based neuroimaging markers and genetic risk factors such as the APOE ε4 allele for cognitive outcomes remains uncertain. The objectives of this study were to estimate the pooled prevalence of cognitive impairment in CSVD, evaluate the associations of key neuroimaging markers (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes) and APOE ε4 with cognitive outcomes, and assess their diagnostic performance. Methods: This study included a systematic review and meta-analysis in accordance with PRISMA and MOOSE guidelines, searching five databases (2005–2025). Eligible studies included adults with CSVD and MRI-visible markers reporting cognitive outcomes (mild cognitive impairment [MCI], global cognitive impairment [GCI], all-cause dementia [ACD], vascular dementia [VaD], and Alzheimer’s disease [AD]). Thirty-nine studies comprising 18,425 participants were included. Pooled prevalence and associations were estimated using random-effects models, and diagnostic accuracy was evaluated. Certainty of evidence was assessed using the GRADE framework. Results: The pooled prevalence of GCI in CSVD was 57% (95% CI: 51–62%), while MCI prevalence was 46% (95% CI: 42–51%). WMHs were strongly associated with VaD (OR 10.35, 95% CI: 7.32–14.64), lacunes with ACD (OR 3.18, 95% CI: 1.24–8.20), and CMBs with AD (OR 1.52, 95% CI: 1.04–2.24). APOE ε4 carriage increased the risk of GCI (OR 1.80, 95% CI: 1.41–2.29). Across markers, diagnostic sensitivity was low, specificity was moderate-to-high, and AUROC values were modest. GRADE certainty ranged from low to moderate, with the highest confidence for WMHs and VaD. Conclusions: CSVD-related MRI markers and APOE ε4 are significantly associated with both early and late cognitive outcomes, supporting the integrated vascular–neurodegenerative continuum. The limited diagnostic sensitivity and variable certainty of evidence highlight the need for harmonized definitions, lesion quantification, and multimodal imaging–genetic approaches to improve early detection and risk stratification of CSVD-related cognitive impairment. Full article

Social media-based content entrepreneurship is evolving rapidly and emerging as a significant and growing form of employment. Generative AI (GenAI) offers content entrepreneurs a powerful tool for content creation; however, the technology can be abused to produce deepfakes, rumors, plagiarism, and other injurious content. This triggers value co-destruction across the creator economy and society, making it particularly crucial to enhance content entrepreneurs’ compliance with GenAI policies. Aiming to develop an effective governance framework, this study adopts a mixed-methods approach, beginning with exploratory interviews to uncover factors affecting GenAI policy compliance intention. Subsequently, it employs confirmatory quantitative research with a survey to validate the proposed research model. The results indicate that both the deterrence triad (i.e., perceived sanction certainty, severity, and celerity) and perceived social norm strengthen GenAI policy compliance intention. Meanwhile, perceived social norm weakens the impact of perceived sanction certainty on policy compliance intention. Furthermore, peer communication enhances policy compliance intention by increasing perceptions of sanction certainty and celerity as well as social norm. These findings contribute to the sustainable development of content entrepreneurship and effective GenAI governance, fostering a symbiotic creator economy. Full article

Objectives: Pulmonary embolism (PE) is an uncommon but potentially fatal complication of acute ischaemic stroke (AIS). Its global burden and prevention remain incompletely defined. We performed a systematic review and meta-analysis (PEARL-AIS) to estimate prevalence, risk factors, outcomes, and prophylactic efficacy, with GRADE evidence appraisal. Methods: Following PRISMA 2020 and MOOSE guidelines, five databases (PubMed, Embase, Cochrane, Scopus, Web of Science) were searched (1995–2024). The protocol was prospectively registered (OSF s25ny). Random-effects models (DerSimonian–Laird; REML sensitivity) were used to pool prevalence and odds ratios; heterogeneity was evaluated with I², Cochran’s Q, and τ². Influence (leave-one-out) and subgroup analyses for prevalence and mortality of PE in AIS were explored. Bias was assessed using the Modified Jadad Scale; overall certainty was graded with the GRADE framework. Results: Twenty-four studies met the inclusion criteria (n = 25,666,067), of which seventeen studies (n = 23,637,708) contributed to pooled prevalence analyses. The pooled prevalence of PE after AIS was 0.40% (95% CI 0.33–0.49), approximately six-fold higher than in the general population, with considerable heterogeneity (I² > 90%, Cochrane classification). The pooled mortality among AIS patients with PE was 12.9% (95% CI 1.6–31.7). Mortality risk was significantly higher in AIS patients with PE (OR 4.96, 95% CI 2.98–8.24). Atrial fibrillation (29%), cancer (19%), and smoking (23%) were common; hypertension (54%) and diabetes (23%) were prevalent but not predictive, with diabetes showing a paradoxical protective association (OR 0.88, 95% CI 0.84–0.92). Pharmacological prophylaxis was associated with a reduced risk of PE (OR 0.64, 95% CI 0.46–0.90; I² = 0%), supported by moderate-certainty evidence. Conclusions: PE is an uncommon but often fatal complication of AIS. Traditional venous thromboembolism predictors underperform in this context, suggesting a stroke-specific thromboinflammatory mechanism linking the brain and lung axis. Despite considerable heterogeneity and low-to-moderate certainty of evidence, pharmacological prophylaxis demonstrates a consistent protective effect. Systematic PE surveillance and tailored prophylactic strategies should be integral to contemporary stroke care, while future studies should refine risk stratification and elucidate the mechanistic underpinnings of this brain–lung thromboinflammatory continuum. Full article

Background: Deep vein thrombosis (DVT) is a serious thromboinflammatory complication of acute ischemic stroke (AIS). The true incidence, mechanistic risk factors, and optimal prophylactic strategies remain uncertain, particularly in the era of reperfusion therapy. Methods: This systematic review and meta-analysis (IRIS-DVT) searched PubMed, Embase, Cochrane, Scopus, and Web of Science for studies reporting DVT incidence, risk factors, or prophylaxis in AIS (2004–2025). Random-effects models were used to generate pooled prevalence and effect estimates, and the certainty of evidence was graded using the GRADE framework. Results: Forty-two studies (n = 6,051,729 patients) were included. The pooled prevalence of DVT was 7% (95% CI, 6–9%), approximately seventy-fold higher than in the general population, with wide heterogeneity influenced by screening timing and diagnostic modality. Pathophysiological risk factors included higher stroke severity (NIHSS; SMD 0.41; 95% CI, 0.38–0.43), older age (SMD 0.32; 95% CI, 0.18–0.46), elevated D-dimer (SMD 0.55; 95% CI, 0.38–0.72), female sex (OR 1.33; 95% CI, 1.19–1.50), and malignancy (OR 2.69; 95% CI, 1.56–5.22), supported by moderate-certainty evidence. Respiratory infection and admission hyperglycemia showed weaker, low-certainty associations. Traditional vascular risk factors (hypertension, diabetes, atrial fibrillation, dyslipidemia) were not significantly related to DVT risk. Evidence for prophylaxis with low-molecular-weight heparin, direct oral anticoagulants, or intermittent pneumatic compression was limited and graded very low certainty. Conclusions: DVT complicates approximately one in fourteen AIS cases, reflecting a distinct thromboinflammatory process driven more by acute neurological severity, systemic hypercoagulability, and malignancy than by conventional vascular risk factors. Early systematic screening (≤72 h) and consistent use of mechanical prophylaxis are warranted. Dedicated AIS-specific mechanistic and interventional trials are urgently needed to refine prevention strategies and improve post-stroke outcomes. Full article

Background/Objectives: This systematic review aimed to evaluate the effectiveness and predictability of lower incisor intrusion with clear aligners in permanent dentition, addressing one of the most challenging aspects of vertical tooth movement control in the mandibular anterior region. Methods: A comprehensive literature search was conducted across five databases (PubMed, Scopus, Embase, and Cochrane) according to PRISMA guidelines. Eight clinical studies fulfilled the eligibility criteria. Risk of bias was assessed using ROBINS-I, and certainty of evidence was graded with GRADE. Key outcomes included the amount of achieved versus planned intrusion, predictability, treatment protocols, use of auxiliaries, and patient-related factors such as age and compliance. Results: Reported mean intrusion values ranged from 0.4 to 1.5 mm, with predictability between 35% and 65%. The effectiveness of intrusion was influenced by the magnitude of planned movement, auxiliaries (e.g., attachments, elastics), refinement strategies, and patient-specific factors. Substantial heterogeneity was present in measurement methods (CBCT, cephalometry, digital models) and clinical protocols (aligner change intervals, refinement frequency), preventing meta-analysis. Seven of the eight studies were rated as having a serious risk of bias, and the overall certainty of evidence was moderate to low. Long-term outcomes and patient-centered measures were not adequately assessed. Conclusions: Within the limitations of the available evidence, lower incisor intrusion with clear aligners may be considered a feasible orthodontic option when supported by biomechanically informed clinical management. However, conclusions should be interpreted with caution due to heterogeneity, high risk of bias, and lack of long-term data. Further standardized studies with longer follow-up are required to strengthen reliability and clinical applicability. Full article