Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression.

Periodontitis is a highly prevalent disease characterized by inflammation and destruction of tooth-supporting tissues that leads to tooth loss in extreme situations. Elucidating the underlying mechanisms of periodontitis pathogenesis and progression will establish the groundwork for developing effective treatment strategies. Recently, evidence concerning the role of ferroptosis in periodontitis progression has emerged. Osteogenic lineage cells are key regulators of bone remodeling. Osteogenic cell death, as observed in experimental periodontitis models, disrupts the balance between bone resorption and bone formation. However, whether the osteogenic lineage undergoes ferroptosis during periodontitis and the corresponding effect on periodontitis progression remain elusive. Here, we investigated cell-specific ferroptosis within the alveolar bone in a murine periodontitis model. Through immunofluorescence double staining and immunohistochemistry, we identified ferroptotic osteocytes and osteoblasts in inflammatory alveolar bone. Next, in vivo administration of erastin or liproxstatin-1 was conducted to either induce or inhibit ferroptosis, respectively. Severe bone resorption and inflammation, accompanied by increased osteoclast formation and impaired osteogenic potential were detected following ferroptosis activation. Subsequently, we carried out in vitro experiments on osteocytes and further verified that ferroptosis enhanced the osteocytic expression of RANKL and IL-6. These findings suggest that ferroptosis occurring within the osteogenic lineage acts as a catalyst in the progression of periodontitis by stimulating osteoclastogenesis through the secretion of inflammatory cytokines and inhibiting osteoblastic function, providing insights into ferroptosis-induced alterations in microenvironment-based intercellular communication. Ferroptosis is a promising target for controlling inflammation and preventing bone resorption in periodontitis.

An angiogenesis-associated gene-based signature predicting prognosis and immunotherapy efficacy of head and neck squamous cell carcinoma patients.

OBJECTIVES: To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples. RESULTS: We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation. CONCLUSION: We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.

Dental Rehabilitation of the Unilateral Cleft Dental Gap: A Single Institution Experience With Long-Term Follow-Up.

OBJECTIVE: The purpose of this study was to identify factors associated with the management of the cleft dental gap after alveolar bone grafting. METHODS: This was a retrospective cohort study of patients with unilateral cleft lip and alveolus or palate who had successful alveolar bone grafting. Our primary study outcome was alveolar cleft management (orthodontic closure or space maintenance). Our secondary study outcome was the rate of fixed dental rehabilitation. Univariate comparisons were made with SAS 9.4. RESULTS: The final study sample consisted of 54 patients. Most patients were treated with orthodontic closure (55.6%). Patients missing multiple teeth ( P < 0.01) were less likely to receive orthodontic closure. Orthodontic closure was not associated with differences in intermaxillary midline coincidence ( P = 0.22) or the need for LeFort advancement ( P = 0.15). Only 41.7% of patients who were managed with space maintenance obtained a fixed prosthesis. Hispanic ethnicity ( P < 0.01) and Medicaid insurance ( P < 0.01) were associated with lower rates of fixed dental rehabilitation. CONCLUSIONS: Orthodontic closure was the most common approach, and it did not result in significant maxillary midline distortion. Less than half of patients treated with space maintenance obtained fixed restorations. Socioeconomic barriers are likely preventing access to definitive dental rehabilitation in patients with unilateral cleft lip and alveolus or palate.

You are not lab rats at teaching hospitals: A systematic review of resident and fellow participation leads to improved colonoscopy.

BACKGROUND: Participation in colonoscopies is an essential aspect of endoscopic training. The purpose of this study was to explore the impact of fellow/trainee participation on colonoscopy outcomes. METHODS: This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). From database inception to July 2022, studies investigating fellow involvement and colonoscopy outcomes were searched across Cochrane library, PubMed, and other databases. The random-effects model was applied to generate more conservative estimates. Sensitive analysis was conducted to explore whether the result would depend on a particular study. Egger's test and Begg's test were used to estimate the potential for publication bias. RESULTS: Seventeen studies including 30,062 participants were included. We found that fellow/trainee involvement enhanced the overall rates of adenoma detection and polyp detection (OR = 1.26, 95% CI = 1.14-1.40, p < 0.001; OR = 1.29, 95% CI = 1.02-1.63, p = 0.020, respectively). The mean number of adenoma/polyps per colonoscopy was also higher with fellow/trainee participation (MD = 0.12, 95% CI = 0.08-0.17, p < 0.001; MD = 0.15, 95% CI = 0.02-0.28, p = 0.020, respectively). CONCLUSION: In addition to its educational purpose, fellow or trainee involvement is associated with beneficial effects on colonoscopy outcomes.

Corrigendum: A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: a real-world retrospective study.

[This corrects the article DOI: 10.3389/fnins.2023.1130831.].

Association between diabetes status and breast cancer in US adults: findings from the US National Health and Nutrition Examination Survey.

Objectives: The aim of this study was to investigate the association between diabetes status and the risk of breast cancer among adult Americans, exploring the impact of BMI, age, and race on this relationship. Methods: A cross-sectional analysis of 8,249 individuals from the National Health and Nutrition Examination Survey (NHANES) was conducted. Diabetes was categorized as type 2 diabetes and prediabetes, with both conditions diagnosed according to the ADA 2014 guidelines. The association between diabetes status and breast cancer risk was explored using multiple logistic regression analysis. Results: Patients with diabetes had higher odds of breast cancer (OR: 1.51; 95% CI 1.00 to 2.28), Using the two-piecewise linear regression model, it was observed that there is a threshold effect in the risk of breast cancer occurrence at the age of 52 years. Specifically, the risk of breast cancer is relatively low before the age of 52 but increases significantly after this age. Conclusions: This study identified a significant association between diabetes status and breast cancer risk among adult Americans. We also found a threshold effect in breast cancer occurrence at the age of 52. Age was significantly associated with breast cancer risk in both Non-Hispanic White and Non-Hispanic Black individuals. These findings underscore the importance of diabetes management, maintaining a healthy BMI, and age-related risk considerations in reducing breast cancer risk.

Association of sugar-sweetened beverages with the risk of colorectal cancer: a systematic review and meta-analysis.

The association between sugar-sweetened beverages intake and colorectal cancer (CRC) remains controversial. A metaanalysis was performed to clarify the correlation between sugar-sweetened beverages and CRC risk/mortality. A systematic literature search was conducted in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform, and China Science and Technology Journal VIP database. Articles were restricted to be available in any language until March 31, 2022. The highest exposed categories were used to calculate the pooled relative risks (RR) values. Pooled relative risks (RR) and 95% confidence intervals (CI) were used to estimate the association of sugar-sweetened beverages with CRC risk and mortality. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic. A total of 17 studies (6 case-control and 11 cohort) involving 557,391 subjects were included in this meta-analysis. The pooled RRs for CRC incidence and mortality among people taking sugar-sweetened beverages were 1.17 (95% CI: 1.07-1.28) and 1.13 (95% CI: 0.99-1.29), respectively. In subgroup analysis, a correlation was found in the distal colon with a pooled RR of 1.41 (95% CI: 1.10-1.80). There was no correlation in the proximal colon with a pooled RR of 1.58 (95% CI: 0.79-3.17). We found statistically significant associations between CRC incidence and sugar-sweetened beverages intake in North America and Oceania, with pooled RRs of 1.16 (95% CI: 1.00-1.33) and 1.32 (95% CI: 1.13-1.55), respectively. In sensitivity analysis, after excluding each study and calculating heterogeneity and effect sizes, there was still a correlation between sugar-sweetened beverages intake and CRC risk. This meta-analysis suggests that sugar-sweetened beverages intake may increase CRC risk, independent of CRC mortality. Whether CRC risk increases with increased sugar-sweetened beverage intake needs further investigation in the future. This meta-analysis aimed to indicate the relationship between sugar-sweetened beverages intake and the risk and mortality of colorectal cancer. A total of 17 studies involving 557,391 subjects were included. The results showed that sugar-sweetened beverages may increase the risk of colorectal cancer but may not be associated with colorectal cancer mortality.

Clinical Features and Prognosis of Uncommon Metastatic Breast Cancer: A Retrospective Analysis of 82 Cases.

With the improvement of diagnostic techniques, numerous uncommon metastases derived from breast cancer were reported. However, very few studies explored the clinical characteristics and prognostic patterns of these patients. A total of 82 cases of uncommon metastatic breast cancer (MBC) registered at our hospital from January 1, 2010, to July 1, 2022, were selected for this retrospective study. The diagnoses of uncommon metastases were based on pathology, and the potential prognostic indicators (overall survival [OS], uncommon disease-free interval [uDFI], and remaining survival [RS]) were estimated. The uncommon metastases involved distant soft tissue, parotid gland, thyroid, digestive system, urinary system, reproductive system, bone marrow, and pericardium. Stepwise multivariate Cox regression analysis indicates age ≤ 35 is an independent risk factor of poor outcome of OS, uDFI, and RS in uncommon MBC patients. Meanwhile, uncommon metastasis combined with common visceral metastasis is an independent risk factor for poor RS of uncommon MBC patients, with a hazard ratio of 6.625 (95% confidence interval = 1.490-29.455, P = .013). Post hoc pairwise comparisons showed that uncommon MBC patients who developed bone-only metastasis survived longer than those concomitant with common visceral metastasis (P = .029). Although the incidence is low, uncommon MBC may involve multiple metastatic sites. The delayed diagnosis of uncommon metastases could lead to systemic progression of the disease. However, patients who only develop uncommon metastasis have a significantly better prognosis than that of those combined with common visceral metastasis. Even for those complicated by bone-only metastasis, active treatment of bone metastases can still achieve substantially longer survival.

A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: A real-world retrospective study.

Background and purpose: Recurrent stroke accounts for 25-30% of all preventable strokes, and this study was conducted to establish a machine learning-based clinical predictive rice idol for predicting stroke recurrence within 1 year in patients with acute ischemic stroke (AIS). Methods: A total of 645 AIS patients at The Second Affiliated Hospital of Xuzhou Medical University were screened, included and followed up for 1 year for comprehensive clinical data. Univariate and multivariate logistic regression (LR) were used to screen the risk factors of stroke recurrence. The data set was randomly divided into training set and test set according to the ratio of 7:3, and the following six prediction models were established by machine algorithm: random forest (RF), Naive Bayes model (NBC), decision tree (DT), extreme gradient boosting (XGB), gradient boosting machine (GBM) and LR. The model with the strongest prediction performance was selected by 10-fold cross-validation and receiver operating characteristic (ROC) curves, and the models were investigated for interpretability by SHAP. Finally, the models were constructed to be visualized using a web calculator. Results: Logistic regression analysis showed that right hemisphere, homocysteine (HCY), C-reactive protein (CRP), and stroke severity (SS) were independent risk factors for the development of stroke recurrence in AIS patients. In 10-fold cross-validation, area under curve (AUC) ranked from 0.777 to 0.959. In ROC curve analysis, AUC ranged from 0.887 to 0.946. RF model has the best ability to predict stroke recurrence, and HCY has the largest contribution to the model. A web-based calculator https://mlmedicine-re-stroke2-re-stroke2-baylee.streamlitapp.com/ has been developed accordingly. Conclusion: This study identified four independent risk factors affecting recurrence within 1 year in stroke patients, and the constructed RF-based prediction model had good performance.

Micro-nano porous structured tantalum-coated dental implants promote osteogenic activity in vitro and enhance osseointegration in vivo.

Due to its excellent biocompatibility and corrosion resistance, tantalum demonstrates versatility as an implant material. However, limited studies investigated the role of tantalum coated titanium-based dental implants. This study aimed to investigate the potential application of micro-nano porous structured tantalum coating on the surface of titanium dental implant. In the present study, micro-nano porous structured tantalum coating was prepared by vacuum plasma spraying (VPS) under selected optimum parameters, various characteristics of tantalum coating (Ta/Ti), including the morphology, potential, constituent, and hydrophilia, were investigated in comparison with its respective control groups, sandblasted titanium (Ti) and titanium coating (Ti/Ti). The adhesion, proliferation, and osteogenic differentiation ability of rat bone marrow mesenchymal cells (BMSCs) on different materials were assessed in vitro. Then the osseointegration capacity of Ti, Ti/Ti, Ta/Ti, and Straumann implants in canine mandible was evaluated with micro-CT, histological sections, and energy dispersive X-ray spectroscopy. These results demonstrated that micro-nanostructured, uneven, and granular tantalum coating was successfully prepared on titanium substrate by VPS with pore size ranging from 50 nm to 5 µm and thickness ranging from 80 to 100 µm. Tantalum coating revealed the highest surface potential, best hydrophilia, and most protein adsorption among Ta/Ti, Ti/Ti, and Ti. Furthermore, Ta/Ti surfaces significantly promoted the adhesion, proliferation, and osteogenic differentiation of BMSCs. In vivo, Ta/Ti implants displayed positive osseointegration capability associated with increased bone mineral density and formation of new bone around implants without tantalum particles released. Together, these findings indicate that tantalum-coated titanium dental implants may serve as a new type of dental implant.

Refractory diarrhea in a patient with Sjogren's syndrome: A case report.

We present the case of a 66-year-old man with no abdominal symptoms other than chronic refractory diarrhea. Other causes for diarrhea were excluded. The positive results of anti-SSA antibodies, Schirmer's test, and the biopsy of minor salivary glands confirmed the diagnosis of Sjogren's syndrome. Moreover, during the course of treatment, the patient developed refeeding syndrome. His diarrhea and nutrition resolved with initiation of glucocorticoids. This case highlights that chronic refractory diarrhea can be the chief complaint and most severe symptom in patients with Sjogren's syndrome.

Association between household air pollution and all-cause and cause-specific mortality: a systematic review and meta-analysis.

Recently, a growing number of epidemiological studies have examined the relationship between household air pollution (HAP) and all-cause and cause-specific mortality. While the results were not entirely consistent, the current study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol to conduct a comprehensive review and meta-analysis. Data sources were PubMed, Web of Science, Embase, and Cochrane Library for studies published up to 12 May 2022. The pooled relative risks (RRs) with 95% confidence intervals (CI) were used to estimate the effect of household air pollution on all-cause and cause-special mortality. Then I square value (I2) was used to assess heterogeneity, and random-effects model was used as the pooling method. Seventeen studies were included in the quantitative analysis. Our results showed a significant association between household air pollution and increased risks of all-cause mortality (RR = 1.12, 95% CI = 1.06-1.19) and cardiovascular disease mortality (RR = 1.13, 95% CI = 1.04-1.24). Similarly, the associations between household air pollution and mortality from other specific causes (respiratory, ischemic heart disease, stroke, and total cancer) were positive, although they were not statistically significant. The study suggests that exposure to household air pollution increases the risk of all-cause mortality and cardiovascular disease mortality. In addition, our results found a trend of increased mortality from the respiratory system, ischemic heart disease, stroke, and total cancer, with household air pollution.

SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19.

Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants.

Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. METHODS: We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. RESULTS: Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. CONCLUSION: The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.

Hyperion imaging system reveals heterogeneous tumor microenvironment of oral squamous cell carcinoma patients at T1N0M0 stage.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a highly heterogeneous neoplasm where the identification of heterogeneity is a critical clinical need to improve treatment planning and prognosis prediction. Utilizing the Hyperion imaging system to carry out high-dimensional proteomics analysis on the heterogeneity of tumor samples, this study aims to detect and analyze the heterogeneity of OSCC without lymph node metastasis and explore potential contributing factors for poor prognosis of early-stage OSCC. METHODS: We collected tumor tissue samples from four OSCC patients at the T1N0M0 stage, who presented with similar clinical manifestations. Patient formalin-fixed, paraffin-embedded (FFPE) tissue sections were prepared and stained using a panel of 26 immune or tumor-related antibodies. Different metal tags were assigned to each antibody. The stained cells were then detected and analyzed by the Hyperion imaging system. RESULTS: Tumor samples of four OSCC patients presenting with similar clinical characteristics at the T1N0M0 stage had different cell subtypes, including CD4+ T cells, CD8+ T cells, CD19+ B cells, CD11c+ dendritic cells, CD56+ natural killer cells, granulocytes, etc. More immunosuppressive cells were found in the sample of patient 1. We propose that differences in the tumor microenvironment of samples may contribute to different patients' prognosis in the future. CONCLUSIONS: High-dimensional proteomics analyses using the Hyperion imaging system help identify and analyze the tumor microenvironment heterogeneity of OSCC. Our study now presents this valuable resource and explains the potential reasons behind early OSCC patients' poor prognosis.

Pruritus in neuromyelitis optica spectrum disorders and multiple sclerosis.

PURPOSE: Differential diagnosis between neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) at early stage remains challenging at present. Pruritus is reported as a common or specific feature in NMOSD with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). We aim to verify whether pruritus can help in distinguishing NMOSD from MS. METHODS: We retrospectively reviewed the medical records of consecutive cases of NMOSD and MS patients, demographic data, clinical features, whether or not had pruritus, serum AQP4-IgG status and magnetic resonance imaging (MRI) results. RESULTS: 21.0% (22/105) of NMOSD patients and 2.1% (2/96) of MS patients reported pruritus during disease course (p < 0.01). 20.5% (18/88) of AQP4-IgG positive and 23.5% (4/17) of AQP4-IgG negative NMOSD patients reported pruritus during disease course (p = 0.775). 12.4% (13/105) of NMOSD and 1.0% (1/96) of MS patients reported pruritus at the first attack episode of disease (p < 0.01). 20.0% (21/105) of NMOSD and 1.0% (1/96) of MS patients reported pruritus at the first and second attack episodes of disease (p < 0.01). CONCLUSION: Pruritus is a common and relatively specific feature in either AQP4-IgG positive or negative NMOSD. Pruritus occurs more frequently in NMOSD than MS, which may help in distinguishing NMOSD from MS, especially at early stage.