Underdetected dispersal and extensive local transmission drove the 2022 mpox epidemic.

The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.

Academics are more specific, and practitioners more sensitive, in forecasting interventions to strengthen democratic attitudes.

Concern over democratic erosion has led to a proliferation of proposed interventions to strengthen democratic attitudes in the United States. Resource constraints, however, prevent implementing all proposed interventions. One approach to identify promising interventions entails leveraging domain experts, who have knowledge regarding a given field, to forecast the effectiveness of candidate interventions. We recruit experts who develop general knowledge about a social problem (academics), experts who directly intervene on the problem (practitioners), and nonexperts from the public to forecast the effectiveness of interventions to reduce partisan animosity, support for undemocratic practices, and support for partisan violence. Comparing 14,076 forecasts submitted by 1,181 forecasters against the results of a megaexperiment (n = 32,059) that tested 75 hypothesized effects of interventions, we find that both types of experts outperformed members of the public, though experts differed in how they were accurate. While academics' predictions were more specific (i.e., they identified a larger proportion of ineffective interventions and had fewer false-positive forecasts), practitioners' predictions were more sensitive (i.e., they identified a larger proportion of effective interventions and had fewer false-negative forecasts). Consistent with this, practitioners were better at predicting best-performing interventions, while academics were superior in predicting which interventions performed worst. Our paper highlights the importance of differentiating types of experts and types of accuracy. We conclude by discussing factors that affect whether sensitive or specific forecasters are preferable, such as the relative cost of false positives and negatives and the expected rate of intervention success.

Zoom out: An intervention on the virtual learning environment improves minority students' grades in two field experiments in Israel.

Closing the achievement gap for minority students in higher education requires addressing the lack of belonging these students experience. This paper introduces a psychological intervention that strategically targets key elements within the learning environment to foster the success of minority students. The intervention sought to enhance Palestinian minority student's sense of belonging by increasing the presence of their native language. We tested the effectiveness of the intervention in two field experiments in Israel (n > 20,000), at the height of the COVID-19 pandemic when all classes were held via Zoom. Lecturers in the experimental condition added a transcript of their names in Arabic to their default display (English/Hebrew only). Our findings revealed a substantial and positive impact on Palestinian student's sense of belonging, class participation, and overall grades. In experiment 1, Palestinian student's average grade increased by 10 points. In experiment 2, there was an average increase of 4 points among Palestinian students' semester grade. Our intervention demonstrates that small institutional changes when carefully crafted can have a significant impact on minority populations. These results have significant implications for addressing educational disparities and fostering inclusive learning environment.

Mortality risk information and health-seeking behavior during an epidemic.

In a context where pessimistic survival perceptions have been widespread as a result of the HIV/AIDS epidemic (Fig. 1 A), we study vaccine uptake and other health behaviors during the recent COVID-19 pandemic. Leveraging a longitudinal cohort study in rural Malawi that has been followed for up to 25 y, we document that a 2017 mortality risk information intervention designed to reduce pessimistic mortality perceptions (Fig. 1 B) resulted in improved health behavior, including COVID-19 vaccine uptake (Fig. 1 C). We also report indirect effects for siblings and household members. This was likely the result of a reinforcing process where the intervention triggered engagement with the healthcare system and stronger beliefs in the efficacy of modern biomedical treatments, which led to the adoption of health risk reduction behavior, including vaccine uptake. Our findings suggest that health information interventions focused on survival perceptions can be useful in promoting health behavior and participation in the formal healthcare system, even during health crises-such as the COVID-19 pandemic-that are unanticipated at the time of the intervention. We also note the importance of the intervention design, where establishing rapport, tailoring the content to the local context, and spending time with respondents to convey the information contributed to the salience of the message.

Masks and respirators for prevention of respiratory infections: a state of the science review.

SUMMARYThis narrative review and meta-analysis summarizes a broad evidence base on the benefits-and also the practicalities, disbenefits, harms and personal, sociocultural and environmental impacts-of masks and masking. Our synthesis of evidence from over 100 published reviews and selected primary studies, including re-analyzing contested meta-analyses of key clinical trials, produced seven key findings. First, there is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Second, masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect. Third, respirators are significantly more effective than medical or cloth masks. Fourth, mask mandates are, overall, effective in reducing community transmission of respiratory pathogens. Fifth, masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation. Sixth, while there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably D/deaf people) are disadvantaged when others are masked. Finally, there are risks to the environment from single-use masks and respirators. We propose an agenda for future research, including improved characterization of the situations in which masking should be recommended or mandated; attention to comfort and acceptability; generalized and disability-focused communication support in settings where masks are worn; and development and testing of novel materials and designs for improved filtration, breathability, and environmental impact.

A marginal structural model for normal tissue complication probability.

The goal of radiation therapy for cancer is to deliver prescribed radiation dose to the tumor while minimizing dose to the surrounding healthy tissues. To evaluate treatment plans, the dose distribution to healthy organs is commonly summarized as dose-volume histograms (DVHs). Normal tissue complication probability (NTCP) modeling has centered around making patient-level risk predictions with features extracted from the DVHs, but few have considered adapting a causal framework to evaluate the safety of alternative treatment plans. We propose causal estimands for NTCP based on deterministic and stochastic interventions, as well as propose estimators based on marginal structural models that impose bivariable monotonicity between dose, volume, and toxicity risk. The properties of these estimators are studied through simulations, and their use is illustrated in the context of radiotherapy treatment of anal canal cancer patients.

Correlation between the dynamic changes of γδT cells, Th17 cells, CD4+CD25+ regulatory T cells in peripheral blood and pharmacological interventions against bleomycin-induced pulmonary fibrosis progression in mice.

The involvement of γδT cells, Th17 cells, and CD4+CD25+ regulatory T cells (Tregs) is crucial in the progression of pulmonary fibrosis (PF), particularly in maintaining immune tolerance and homeostasis. However, the dynamics of these cells in relation to PF progression, especially under pharmacological interventions, remains poorly understood. This study aims to unravel the interplay between the dynamic changes of these cells and the effect of pharmacological agents in a mouse model of PF induced by intratracheal instillation of bleomycin. We analyzed changes in lung histology, lung index, hydroxyproline levels, and the proportions of γδT cells, Th17 cells, and Tregs on the 3rd, 14th, and 28th days following treatment with Neferine, Isoliensinine, Pirfenidone, and Prednisolone. Our results demonstrate that these drugs can partially or dynamically reverse weight loss, decrease lung index and hydroxyproline levels, and ameliorate lung histopathological damage. Additionally, they significantly modulated the abnormal changes in γδT, Th17, and Treg cell proportions. Notably, on day 3, the proportion of γδT cells increased in the Neferine and Prednisolone groups but decreased in the Isoliensinine and Pirfenidone groups, while the proportion of Th17 cells decreased across all treated groups. On day 14, the Neferine group showed an increase in all three cell types, whereas the Pirfenidone group exhibited a decrease. In the Isoliensinine group, γδT and Th17 cells increased, and in the Prednisolone group, only Tregs increased. By day 28, an increase in Th17 cell proportion was observed in all treatment groups, with a decrease in γδT cells noted in the Neferine group. These shifts in cell proportions are consistent with the pathogenesis changes induced by these anti-PF drugs, suggesting a correlation between cellular dynamics and pharmacological interventions in PF progression. Our findings imply potential strategies for assessing the efficacy and timing of anti-PF treatments based on these cellular changes.

Who Transmits Tuberculosis to Whom: A Cross-Sectional Analysis of a Cohort Study in Lima, Peru.

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care.

Transcatheter treatment of the tricuspid valve: current status and perspectives.

Transcatheter tricuspid valve interventions (TTVI) are emerging as alternatives to surgery in high-risk patients with isolated or concomitant tricuspid regurgitation. The development of new minimally invasive solutions potentially more adapted to this largely undertreated population of patients, has fuelled the interest for the tricuspid valve. Growing evidence and new concepts have contributed to revise obsolete and misleading perceptions around the right side of the heart. New definitions, classifications, and a better understanding of the disease pathophysiology and phenotypes, as well as their associated patient journeys have profoundly and durably changed the landscape of tricuspid disease. A number of registries and a recent randomized controlled pivotal trial provide preliminary guidance for decision-making. TTVI seem to be very safe and effective in selected patients, although clinical benefits beyond improved quality of life remain to be demonstrated. Even if more efforts are needed, increased disease awareness is gaining momentum in the community and supports the establishment of dedicated expert valve centres. This review is summarizing the achievements in the field and provides perspectives for a less invasive management of a no-more-forgotten disease.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations.

Cancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized-combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.

Shape-constrained deformable brain segmentation: Methods and quantitative validation.

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions.

Exploring the Therapeutic Potential: Bioactive Molecules and Dietary Interventions in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS.

Positive Effects of Physical Activity on Insulin Signaling.

Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve glycemic control, highlighting exercise as a recommended therapeutic strategy for reducing insulin resistance. Physical inactivity is closely linked to islet cell insufficiency, exacerbating insulin resistance through various pathways including ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. Conversely, physical training and exercise preserve and restore islet function, enhancing peripheral insulin sensitivity. Exercise interventions stimulate ß-cell proliferation through increased circulating levels of growth factors, further emphasizing its role in maintaining pancreatic health and glucose metabolism. Furthermore, sedentary lifestyles contribute to elevated oxidative stress levels and ceramide production, impairing insulin signaling and glucose metabolism. Regular exercise induces anti-inflammatory responses, enhances antioxidant defenses, and promotes mitochondrial function, thereby improving insulin sensitivity and metabolic efficiency. Encouraging individuals to adopt active lifestyles and engage in regular exercise is crucial for preventing and managing insulin resistance and related metabolic disorders, ultimately promoting overall health and well-being.

Interventional Pharmacoepidemiology: Design and evaluation of interventions to improve prescribing.

Despite the value of modern therapeutics, many obstacles prevent their optimal use. Overuse, underuse and misuse are common, resulting in morbidity and mortality impacting billions of individuals across the world. Pharmacoepidemiology provides important insights into drug utilization, safety and effectiveness in large populations, and it is an important method to identify opportunities to improve the value of therapeutics in clinical practice. However, for these opportunities to be realized, interventions to improve prescribing must be developed, evaluated and implemented in the real world. We provide an overview of this process, focusing especially on how such interventions can be designed and deployed to maximize scalability, adoption and impact. Prescribing represents a complex behavior with barriers and enablers, and interventions to improve prescribing will be most successful when developed, piloted and refined to maximize provider and patient acceptability. Carefully developed evaluations of interventions are also critical, and varied methods are available to empirically evaluate the intended and potential unintended consequences of interventions. With illustrative examples from the peer-reviewed literature, we provide readers with an overview of approaches to the essential and growing field of interventional pharmacoepidemiology.

Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases.

Cuproptosis, a newly characterized form of regulated cell death driven by copper accumulation, has emerged as a significant mechanism underlying various non-cancerous diseases. This review delves into the complex interplay between copper metabolism and the pathogenesis of conditions such as Wilson's disease (WD), neurodegenerative disorders, and cardiovascular pathologies. We examine the molecular mechanisms by which copper dysregulation induces cuproptosis, highlighting the pivotal roles of key copper transporters and enzymes. Additionally, we evaluate the therapeutic potential of copper chelation strategies, which have shown promise in experimental models by mitigating copper-induced cellular damage and restoring physiological homeostasis. Through a comprehensive synthesis of recent advancements and current knowledge, this review underscores the necessity of further research to translate these findings into clinical applications. The ultimate goal is to harness the therapeutic potential of targeting cuproptosis, thereby improving disease management and patient outcomes in non-cancerous conditions associated with copper dysregulation.

The superior frontal sulcus in the human brain: Morphology and probability maps.

The superior frontal sulcus (SFS) is the major sulcus on the dorsolateral frontal cortex that defines the lateral limit of the superior frontal gyrus. Caudally, it originates near the superior precentral sulcus (SPRS) and, rostrally, it terminates near the frontal pole. The advent of structural neuroimaging has demonstrated significant variability in this sulcus that is not captured by the classic sulcal maps. The present investigation examined the morphological variability of the SFS in 50 individual magnetic resonance imaging (MRI) scans of the human brain that were registered to the Montreal Neurological Institute (MNI) standard stereotaxic space. Two primary morphological patterns were identified: (i) the SFS was classified as a continuous sulcus or (ii) the SFS was a complex of sulcal segments. The SFS showed a high probability of merging with neighbouring sulci on the superior and middle frontal gyri and these patterns were documented. In addition, the morphological variability and spatial extent of the SFS were quantified using volumetric and surface spatial probability maps. The results from the current investigation provide an anatomical framework for understanding the morphology of the SFS, which is critical for the interpretation of structural and functional neuroimaging data in the dorsolateral frontal region, as well as for improving the accuracy of neurosurgical interventions.

Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn's disease associated adherent-invasive Escherichia coli infection.

Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their bacterial load and duration of infection. In the case of infection of macrophages with Crohn's disease (CD) associated adherent-invasive Escherichia coli (AIEC), understanding the drivers of pathogen success may allow targeting of cells where AIEC replicate to high levels. Here we show that stratifying immune cells based on their bacterial load identifies novel pathways and therapeutic targets not previously associated with AIEC when using a traditional homogeneous infected population approach. Using flow cytometry-based cell sorting we stratified cells into those with low or high intracellular pathogen loads, or those which were bystanders to infection. Immune cells transcriptomics revealed a diverse response to the varying levels of infection while pathway analysis identified novel intervention targets that were directly related to increasing intracellular AIEC numbers. Chemical inhibition of identified targets reduced AIEC intracellular replication or inhibited secretion of tumour necrosis factor alpha (TNFα), a key cytokine associated with AIEC infection. Our results have identified new avenues of intervention in AIEC infection that may also be applicable to CD through the repurposing of already available inhibitors. Additionally, they highlight the applicability of immune cell stratification post-infection as an effective approach for the study of microbial pathogens.

Lifestyle interventions with dietary strategies after breast cancer diagnosis: a systematic review.

PURPOSE: Obesity can increase mortality and morbidity in breast cancer survivors. Healthy lifestyle factors such as diet can help manage weight in this population. This systematic review examined lifestyle interventions with dietary strategies for breast cancer survivors and their effect on diet and/or weight-related outcomes. METHODS: Searches were conducted in Ovid MEDLINE® ALL (1946-February 14, 2022), Embase (Elsevier), CINAHL Complete (EBSCO), and APA PsycArticles (EBSCO), using keywords for diet, breast cancer, and intervention. The search was limited to human studies, English language, and publication processing date 2016-2023. RESULTS: The search yielded 3427 articles. After title and abstract review, 225 full-text articles were screened, and 67 articles with 61 distinct samples and interventions met inclusion criteria. Of these 61 lifestyle interventions with dietary strategies, 43 interventions also addressed physical activity. Most studies were randomized controlled trials (n = 41) and conducted post-treatment (n = 45). Mean participant age was 54 years. Of 29 studies that reported race/ethnicity, 20 (69%) reported ≥50% White participants. Of 36 that reported dietary outcomes, 29 (81%) reported significant findings. Of 57 that reported weight-related outcomes, 51 (89%) reported significant findings. CONCLUSION: This review demonstrated promising evidence for the efficacy of lifestyle interventions with dietary strategies in breast cancer survivors. However, culturally tailored interventions and interventions conducted before and during treatment are lacking.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.