Association between educational attainment and thyroid cancer: evidence from a univariable and multivariable Mendelian randomization study.

BACKGROUND: Thyroid cancer and educational attainment have been related in observational studies. It is unclear if these correlations indicate causative relationships. METHODS: Using large-scale genome-wide association studies (GWAS) datasets, we conducted an univariable and multivariable Mendelian randomization (MR) study to assess a potential connection between educational attainment and thyroid cancer. The inverse-variance weighted (IVW) analysis method is used as our primary outcome. Additionally, we carry out several sensitivity analyses to evaluate the pleiotropy and robustness of the causal estimates. RESULTS: Univariate MR study shows 4.2 years of additional education is associated with a 41.4% reduction in thyroid cancer risk (OR = 0.586; 95% CI: 0.378-0.909; P = 0.017). Further multivariable MR analysis revealed that body mass index (BMI) acted as a partial mediating factor in the protective impact of higher educational attainment against thyroid cancer. CONCLUSION: This MR study provided genetic evidence that longer education attainment is related to a lower risk of thyroid cancer. Strategies of expanding education may reduce the burden of thyroid cancer in the world.

The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

Background: The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. Methods: We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Results: Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. Conclusion: This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

Risk factors of incontinence-associated dermatitis in older adults: a protocol for systematic review and meta-analysis.

INTRODUCTION: Due to their ageing skin, older adults are more likely to develop incontinence-associated dermatitis (IAD). Although previous attempts to look at the risk factors for IAD in older adults were done, methodological barriers hindered an in-depth understanding. By investigating risk factors for IAD in the ageing population, the development of precise clinical interventions and guidance could be facilitated, which in turn would enhance patient care standards for incontinence management in this target group. To address this knowledge gap, this systematic review with meta-analysis aims to explore the major risk elements linked to IAD among older adults. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols are adhered to in this systematic review and meta-analysis. To achieve its objectives, a comprehensive search strategy PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Medline, Chinese Scientific Journal Database (VIP database), WanFang Data Knowledge Service Platform, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, along with other relevant sources published until 18 July 2023 in both English and Chinese languages will be performed. The screening of articles, data abstraction and risk of bias evaluation will be done by two impartial reviewers. RevMan V.5.3 software will be used for data synthesis. The quality of the included study will be assessed using the Newcastle-Ottawa Quality Assessment tool and the Agency for Healthcare Research and Quality. The I 2 test will identify the heterogeneity. ETHICS AND DISSEMINATION: There is no need for ethical approval. Individual patient information or the rights of participants will not be compromised by this protocol. The findings will either be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023442585.

CellBiAge: Improved single-cell age classification using data binarization.

Aging is a major risk factor for many diseases. Accurate methods for predicting age in specific cell types are essential to understand the heterogeneity of aging and to assess rejuvenation strategies. However, classifying organismal age at single-cell resolution using transcriptomics is challenging due to sparsity and noise. Here, we developed CellBiAge, a robust and easy-to-implement machine learning pipeline, to classify the age of single cells in the mouse brain using single-cell transcriptomics. We show that binarization of gene expression values for the top highly variable genes significantly improved test performance across different models, techniques, sexes, and brain regions, with potential age-related genes identified for model prediction. Additionally, we demonstrate CellBiAge's ability to capture exercise-induced rejuvenation in neural stem cells. This study provides a broadly applicable approach for robust classification of organismal age of single cells in the mouse brain, which may aid in understanding the aging process and evaluating rejuvenation methods.

Fertility concerns in cancer patients: a bibliometric analysis via CiteSpace: A review.

Fertility concerns are a pervasive issue but very subtle in patients with cancer. Though various studies have focused on fertility concerns, limited research endeavor has been dedicated to bibliometric analysis. Given this, to visually analyze the hot frontier trends of research related to fertility concerns of patients with cancer using CiteSpace and provide new insights for future research in this field using the bibliometric method. We used CiteSpace software to retrieve the literature related to fertility concerns of patients with cancer in the Web of Science core collection database from the year of establishment to 2022 and conducted visual analysis in terms of authors, countries and regions, research institutions, and keywords. The search resulted in 201 valid articles, and the annual publication volume of literature related to fertility concerns in patients with cancer was generally on the rise; the country with the most publications was the United States, which also had the highest influence; the main research institution was Sloan Kettleson Cancer Research Center; the core research scholar was Jessica R. Gorman; the research hotspots mainly centered on quality of survival, women, survivorship, preservation, breast cancer, adolescence, and infertility. The results of this bibliometric study provide the current status and trends in the fertility concerns of patients with cancer and may help researchers identify the hotspots and frontier trends in this field.

Incidence and influencing factors of fertility concerns in breast cancer in young women: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the prevalence and influencing factors of fertility concerns in breast cancer in young women. Methods: A literature search on PubMed, Embase, Web of Science, and Cochrane Library databases was conducted up to February 2023 and was analyzed (Revman 5.4 software) in this study. The papers were chosen based on inclusion standards, and two researchers independently extracted the data. The included studies' quality was evaluated using criteria set out by the Agency for Healthcare Research and Quality. To identify significant variations among the risk factors, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were utilized. Results: A total of 7 studies that included 1579 breast cancer in young women were enrolled in the study. The results showed that for breast cancer in young women, the incidence of fertility concerns 53%(95%CI [0.45,0.58]). The results showed that education (2.65, 95% CI 1.65-5.63), full-time work (0.12, 95% CI 1.03-1.93), fertility intentions (7.84, 95% CI 1.50-37.4), depression level (1.25, 95% CI 1.03-1.5), and endocrine therapy (1.32, 95% CI 1.08-1.62) were risk factors for fertility concerns in young women with BC. Having a partner (0.41, 95% CI 0.33-0.5), ≥1 child (0.3, 95% CI 0.22-0.4) were identified as protective factors against fertility concerns in young women with BC. Conclusions: The incidence of fertility concerns in breast cancer in young women is at a moderately high level. We should pay more attention to the risk factors of fertility concerns to help breast cancer in young women cope with their fertility concerns and promote their psychological well-being.

Understanding the aging hypothalamus, one cell at a time.

The hypothalamus is a brain region that integrates signals from the periphery and the environment to maintain organismal homeostasis. To do so, specialized hypothalamic neuropeptidergic neurons control a range of processes, such as sleep, feeding, the stress response, and hormone release. These processes are altered with age, which can affect longevity and contribute to disease status. Technological advances, such as single-cell RNA sequencing, are upending assumptions about the transcriptional identity of cell types in the hypothalamus and revealing how distinct cell types change with age. In this review, we summarize current knowledge about the contribution of hypothalamic functions to aging. We highlight recent single-cell studies interrogating distinct cell types of the mouse hypothalamus and suggest ways in which single-cell 'omics technologies can be used to further understand the aging hypothalamus and its role in longevity.

Single-cell analysis of the aging female mouse hypothalamus.

Alterations in metabolism, sleep patterns, body composition, and hormone status are all key features of aging. While the hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors, little is known about the intrinsic features of hypothalamic aging. Here, we perform single nuclei RNA-sequencing of 40,064 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neuronal subtypes as well as astrocytes and microglia. We uncover changes in cell types critical for metabolic regulation and body composition, and in an area of the hypothalamus linked to cognition. Our analysis also reveals an unexpected female-specific feature of hypothalamic aging: the master regulator of X-inactivation, Xist, is elevated with age, particularly in hypothalamic neurons. Moreover, using machine learning, we show that levels of X-chromosome genes, and Xist itself, can accurately predict cellular age. This study identifies critical cell-specific changes of the aging hypothalamus in mammals, and uncovers a potential marker of neuronal aging in females.

COMBINATION OF VITRECTOMY AND INTENTIONAL MACULAR DETACHMENT IS ASSOCIATED WITH A FASTER EDEMATOUS REGRESSION THAN VITRECTOMY ALONE IN THE TREATMENT OF REFRACTORY DIABETIC MACULAR EDEMA.

PURPOSE: To compare clinical outcomes in eyes with refractory diabetic macular edema managed by vitrectomy combined with and without intentional macular detachment (IMD). METHODS: This is a retrospective cohort study. Forty-one eyes with diabetic macular edema that were previously poorly responsive to at least 5 monthly anti-vascular endothelial growth factor and at least twice switch therapy previously were included in this study. All eyes underwent pars plana vitrectomy with internal limiting membrane peeling, 21 of which were combined with an IMD procedure (assigned to an IMD group) and 20 of which did not have IMD performed (nMD group). Macular morphologic and visual acuity changes were analyzed from baseline through the endpoint (24 weeks) postprocedure, and were compared between groups. RESULTS: All patients completed at least six months of follow-up, with a mean of 29.7 weeks (24-56 weeks). The mean central retinal thickness reduction was greater in the IMD group than that in the nMD group at 1 week (P = 0.001), 2 weeks (P = 0.008), and 4 weeks (P = 0.004), but there was no statistically significant difference at 12 weeks (P = 0.051) or 24 weeks (P = 0.056). There were no significant differences in the mean changes of best-corrected visual acuity from baseline to the 24 weeks endpoint in either group (P = 0.83). CONCLUSION: Vitrectomy can release macular edema in the eyes with refractory diabetic macular edema. Combined with IMD technical, patients seemed to achieve a faster central retinal thickness decrease but neither the final morphologic outcome nor the visual acuity was affected.

Reprogramming to recover youthful epigenetic information and restore vision.

Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.

Capping Protein Regulator and Myosin 1 Linker 3 Is Required for Tumor Metastasis.

Metastasis accounts for 90% of deaths caused by solid tumors, but the multitude of mechanisms underlying tumor metastasis remains poorly understood. CARMIL1 and 2 proteins are capping protein (CP) interactants and multidomain regulators of actin-based mobility. However, CARMIL3's function has not been explored. Through bioinformatic metadata analysis, we find that high CARMIL3 expression correlates with poor survival of patients with breast and prostate cancer. Functional studies in murine and xenograft tumor models by targeted diminution of CARMIL3 expression or forced expression demonstrate that CARMIL3 is vitally important for tumor metastasis, especially for metastatic colonization. Consistent with a predominantly cell-intrinsic mode of action, CARMIL3 is also crucial for tumor cell migration and invasion in vitro. Coimmunoprecipitation coupled with mass spectrometric analyses identifies a group of CARMIL3-interacting proteins, including capping protein, that are involved in actin cytoskeletal organization, which is required for cell polarization and focal adhesion formation. Moreover, molecular pathway enrichment analysis reveals that lack of CARMIL3 leads to loss of cell adhesions and low CARMIL3 expression in breast cancer patient specimens is implicated in epithelial-mesenchymal transition. We also find that CARMIL3 sustains adherens junction between tumor cells. This is accomplished by CARMIL3 maintaining E-cadherin transcription downstream of HDACs through inhibiting ZEB2 protein level, also via protecting ß-catenin from ubiquitination-mediated degradation initiated by the destruction complex. IMPLICATIONS: This study uncovers CARMIL3 as a novel and critical regulator of metastatic progression of cancers and suggests therapeutic potentials to target CARMIL3.