Focal cortical dysplasia lesion segmentation using multiscale transformer.

OBJECTIVES: Accurate segmentation of focal cortical dysplasia (FCD) lesions from MR images plays an important role in surgical planning and decision but is still challenging for radiologists and clinicians. In this study, we introduce a novel transformer-based model, designed for the end-to-end segmentation of FCD lesions from multi-channel MR images. METHODS: The core innovation of our proposed model is the integration of a convolutional neural network-based encoder-decoder structure with a multiscale transformer to augment the feature representation of lesions in the global field of view. Transformer pathways, composed of memory- and computation-efficient dual-self-attention modules, leverage feature maps from varying depths of the encoder to discern long-range interdependencies among feature positions and channels, thereby emphasizing areas and channels relevant to lesions. The proposed model was trained and evaluated on a public-open dataset including MR images of 85 patients using both subject-level and voxel-level metrics. RESULTS: Experimental results indicate that our model offers superior performance both quantitatively and qualitatively. It successfully identified lesions in 82.4% of patients, with a low false-positive lesion cluster rate of 0.176 ± 0.381 per patient. Furthermore, the model achieved an average Dice coefficient of 0.410 ± 0.288, outperforming five established methods. CONCLUSION: Integration of the transformer could enhance the feature presentation and segmentation performance of FCD lesions. The proposed model has the potential to serve as a valuable assistive tool for physicians, enabling rapid and accurate identification of FCD lesions. The source code and pre-trained model weights are available at https://github.com/zhangxd0530/MS-DSA-NET . CRITICAL RELEVANCE STATEMENT: This multiscale transformer-based model performs segmentation of focal cortical dysplasia lesions, aiming to help radiologists and clinicians make accurate and efficient preoperative evaluations of focal cortical dysplasia patients from MR images. KEY POINTS: The first transformer-based model was built to explore focal cortical dysplasia lesion segmentation. Integration of global and local features enhances the segmentation performance of lesions. A valuable benchmark for model development and comparative analyses was provided.

The role of fibroblast growth factor-2 in modulating the differentiation of periodontal ligament and alveolar bone-derived stem cells.

OBJECTIVE: This study examined how range concentrations of Fibroblast Growth Factor-2 (FGF-2) influence the differentiation and activity of human-derived periodontal ligament (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs). DESIGN: hPDLSCs and haBMSCs were cultured with varying concentrations of FGF-2 (0, 1, 2.5, 5, 10, 20 ng/mL) and monitored for osteogenic differentiation through alkaline phosphatase (ALP) activity and quantification of gene expression (qRT-PCR) for osteogenesis markers. Additionally, alizarin red staining and a hydroxyproline colorimetric assay evaluated and quantified osteogenic matrix mineralization and collagen deposition. Statistical analyses were performed using one-way ANOVA or two-way ANOVA for multiple comparisons between groups. RESULTS: At low FGF-2 concentrations, hPDLSCs differentiated toward an osteogenic lineage, whereas higher concentrations of FGF-2 inhibited osteogenesis and promoted fibroblastic differentiation. The effect of FGF-2 at the lowest concentration tested (1 ng/mL) led to significantly higher ALP activity than osteogenically induced positive controls at early time points and equivalent RUNX2 expression at early and later time points. FGF-2 supplementation of haBMSC cultures was sufficient, at all concentrations, to increase ALP activity at an earlier time point. Mineralization of haBMSC cultures increased significantly within 5-20 ng/mL FGF-2 concentrations under basal growth media conditions (α-minimal essential medium supplemented with 15 % fetal bovine serum and 1 % penicillin/streptomycin). CONCLUSIONS: FGF-2 has a dual capacity in promoting osteogenic and fibroblastic differentiation within hPDLSCs contingent upon the dosage and timing of administration, alongside supporting osteogenic differentiation in haBMSCs. These findings underscore the need for precision growth factors dosing when considering the design of biomaterials for periodontal regeneration.

Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment.

Objectives: Fibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function. Methods: The study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method. Results: Compared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function. Conclusion: Smaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs.

Determinants of active surveillance uptake in a diverse population-based cohort of men with low-risk prostate cancer: The Treatment Options in Prostate Cancer Study (TOPCS).

BACKGROUND: Active surveillance (AS) is the preferred strategy for low-risk prostate cancer (LRPC); however, limited data on determinants of AS adoption exist, particularly among Black men. METHODS: Black and White newly diagnosed (from January 2014 through June 2017) patients with LRPC ≤75 years of age were identified through metro-Detroit and Georgia population-based cancer registries and completed a survey evaluating factors influencing AS uptake. RESULTS: Among 1688 study participants, 57% chose AS (51% of Black participants, 61% of White) over definitive treatment. In the unadjusted analysis, patient factors associated with initial AS uptake included older age, White race, and higher education. However, after adjusting for covariates, none of these factors was significant predictors of AS uptake. The strongest determinant of AS uptake was the AS recommendation by a urologist (adjusted prevalence ratio, 6.59, 95% CI, 4.84-8.97). Other factors associated with the decision to undergo AS included a shared patient-physician treatment decision, greater prostate cancer knowledge, and residence in metro-Detroit compared with Georgia. Conversely, men whose decision was strongly influenced by the desire to achieve "cure" or "live longer" with treatment and those who perceived their LRPC diagnosis as more serious were less likely to choose AS. CONCLUSIONS: In this contemporary sample, the majority of patients with newly diagnosed LRPC chose AS. Although the input from their urologists was highly influential, several patient decisional and psychological factors were independently associated with AS uptake. These data shed new light on potentially modifiable factors that can help further increase AS uptake among patients with LRPC.

Vitamin D receptor prevents tumour development by regulating the Wnt/ß-catenin signalling pathway in human colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS: In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/ß-catenin signalling (ß-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with ß-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR. RESULTS: The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. ß-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with ß-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of ß-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of ß-catenin, cyclin D1 and LEF-1. CONCLUSIONS: This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/ß-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.

Gray matter atrophy and corresponding impairments in connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.

Five-year follow-up study of a population-based prospective cohort of men with low-risk prostate cancer: the treatment options in prostate cancer study (TOPCS): study protocol.

INTRODUCTION: Active surveillance (AS) is recommended for men with low-risk prostate cancer (LRPC) to reduce overtreatment and to maintain patients' quality of life (QOL). However, whether African American (AA) men can safely undergo AS is controversial due to concerns of more aggressive disease and lack of empirical data on the safety and effectiveness of AS in this population. Withholding of AS may lead to a lost opportunity for improving survivorship in AA men. In this study, peer-reviewed and funded by the US Department of Defense, we will assess whether AS is an equally effective and safe management option for AA as it is for White men with LRPC. METHODS AND ANALYSIS: The project extends follow-up of a large contemporary population-based cohort of LRPC patients (n=1688) with a high proportion of AA men (~20%) and well-characterised baseline and 2-year follow-up data. The objectives are to (1) determine any racial differences in AS adherence, switch rate from AS to curative treatment and time to treatment over 5 years after diagnosis, (2) compare QOL among AS group and curative treatment group over time, overall and by race and (3) evaluate whether reasons for switching from AS to curative treatment differ by race. Validation of survey responses related to AS follow-up procedures is being conducted through medical record review. We expect to obtain 5-year survey from ~900 (~20% AA) men by the end of this study to have sufficient power. Descriptive and inferential statistical techniques will be used to examine racial differences in AS adherence, effectiveness and QOL. ETHICS AND DISSEMINATION: The parent and current studies were approved by the Institutional Review Boards at Wayne State University and Emory University. Since it is an observational study, ethical or safety risks are low. We will disseminate our findings to relevant conferences and peer-reviewed journals.

Choosing active surveillance versus curative treatment in a population-based survey of men with low-risk prostate cancer.

Context: Active Surveillance (AS) is a preferred treatment option for low-risk prostate cancer (LPC) in current practice guidelines. Limited data as to factors influencing men's decision to choose AS. Objective: To identify determinants of initial treatment choice and whether race and geographical location influence the AS decision. Design: Longitudinal cohort study. Setting: Population-based sample recruited from two cancer registries. Patients: Black and white men with newly diagnosed LPC. Instrument: Mailed survey. Main Outcome Measure: Initial treatment choice (AS vs. curative treatment). Results: Of the 1688 eligible patients, 925 (54.8%) recruited from metro-Detroit and 763 (45.2%) from Georgia. Overall, 79.4% were White and 20.6% were Black, with a mean age of 62.8 years (SD=6.9, range 39-78). Regarding initial treatment choice, 56.9% of men chose AS, 23.4% surgery, 16.6% radiation, 1.1% watchful waiting, and 1.7% other treatment. In multivariable analysis, men who reported that their Urologist recommended AS were 56 times more likely to choose AS (OR=56, 95%CI 33-94) compared to men who reported that their Urologist recommended treatment. Similarly, men who reported that the decision was made jointly by doctor and patient or predominately by doctor, were about 2 times more likely to choose AS (OR=1.9, 95%CI 1.2-3.0) compared to men who made the decision alone. Men who believed their "cancer is small", had better health, higher yearly income (>=$70,000), higher prostate cancer knowledge, higher decisional conflict, and lived in metro-Detroit, were more likely to choose AS. In contrast, men who expected to "live longer" with chosen treatment, had friends "with good treatment results", and were influenced by "curing cancer", were less likely to choose AS. There was an interaction between race and "curing cancer" (p=0.005). White men were more likely (OR=3.2, 95%CI 1.2-8.9) to choose AS than Black men when "curing cancer" was not influential in their decision. When "curing cancer" was highly influential, White men were less likely than Black men to choose AS (OR 0.5, 95%CI 0.2-0.9). Conclusions: In this population-based sample, more than half of patients with LPC chose AS. Many factors influenced patient's AS decision with Urologist's AS recommendation being the strongest predictor of patient's AS decision.

P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.

B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline novel or rare P2RY8 missense variants in lupus kindreds or the related antiphospholipid syndrome, including a "de novo" variant in a child with severe nephritis. All variants decreased protein expression, F-actin abundance, and GPCR-RhoA signaling, and those with stronger effects increased AKT and ERK activity and cell migration. Remarkably, P2RY8 was reduced in B cell subsets from some SLE patients lacking P2RY8 gene variants. Low P2RY8 correlated with lupus nephritis and increased age-associated B cells and plasma cells. By contrast, P2RY8 overexpression in cells and mice restrained plasma cell development and reinforced negative selection of DNA-reactive developing B cells. These findings uncover a role of P2RY8 in immunological tolerance and lupus pathogenesis.

Progressive cortical and sub-cortical alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Advanced structural analyses are increasingly being highly valued to uncover pathophysiological understanding of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Therefore, we aimed to explore whether and how antibody-mediated NMDAR dysfunction affected cortical and sub-cortical brain morphology and their relationship with clinical symptoms. METHODS: We performed surface-based morphometry analyses, hippocampal segmentation, and correlational analyses in 24 patients with anti-NMDAR encephalitis after acute disease stage and 30 normal controls (NC) in this case-control study. RESULTS: Patients showed significantly decreased cortical alterations mainly in language network (LN) and default mode network (DMN), as well as decreased gray matter volume in left cornu ammonis 1 (CA1) body of hippocampus. Further correlation analyses showed that the decreased cortical thickness in the right superior frontier gyrus was associated with decreased cognitive scores, the decreased cortical volume in the right pars triangulari and decreased surface area in the right pars operculari were associated with decreased memory scores, whereas decreased gray matter volume in the left CA1 body was significantly correlated with longer time between first symptom and imaging in the patients. CONCLUSION: These results suggested that cognitive impairments resulted from long-term sequelae of the encephalitis were mainly associated with cortical alterations in LN and DMN and sub-cortical atrophy of left CA1 body, which can be served as effective features to assess disease progression in clinical routine examination.

Urologists' Perceptions of Active Surveillance and Their Recommendations for Low-risk Prostate Cancer Patients.

OBJECTIVE: To assess practicing urologists' attitudes and perceptions of active surveillance (AS) and other treatment options for low-risk prostate cancer. METHODS: This was a cross-sectional survey of urologists practicing in Michigan and Georgia. Urologists were asked about perceptions and practices pertaining to AS. RESULTS: Overall, 225 urologists completed the survey; 147 (65%) were from Michigan and 78 (35%) were from Georgia. Most urologists reported they provided (99%), discussed (97%), and offered (61%) AS to all of their low-risk patients. Most believed AS is effective (97%) and underused (90%), while 80% agreed that curative therapy (surgery, radiation) is overused in the United States. Although most (79%) endorse that Black men are more likely to have aggressive low-risk disease, 89% reported feeling comfortable recommending AS to Black men. In multivariable analysis, significant provider-related predictors of AS recommendation were practice location, number of years in practice, beliefs pertaining to survival benefit of prostatectomy and effectiveness of AS, and expectation that patients are not interested in AS. The patient characteristics of race, age, life expectancy, fear of cancer progression, and fear of treatment side effects were also significant predictors of AS recommendations. CONCLUSION: Most urologists surveyed stated that AS is effective and underused for low-risk prostate cancer . Overall, urologists are much less likely to recommend AS to younger men and slightly less to Black men. AS recommendations varied by practice location and by years in practice. These findings indicate targeted educational efforts in the US are needed to influence urologists toward greater acceptance of AS.

circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data (P < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis (P = 0.005) and advanced clinical stage (P = 0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, P < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.

Exosomes carrying ALDOA and ALDH3A1 from irradiated lung cancer cells enhance migration and invasion of recipients by accelerating glycolysis.

Lung cancer has been recognized as the leading cause of cancer-related death worldwide. Despite the improvements of treatment, the distant metastasis and recurrence of lung cancer caused by therapy resistance is the biggest challenge in clinical management. Extracellular vesicles named exosomes play crucial roles in intercellular communication as signaling mediators and are involved in tumor development. In this study, we isolated exosomes from irradiated lung cancer cells and co-cultured the exosomes with other lung cancer cells. It was found that cellular growth and motility of recipient cells were facilitated. High-throughput LC-MS/MS assay of exosomal proteins and Gene Ontology enrichment analyses indicated that the metabolic enzymes ALDOA and ALDH3A1 had potential contribution in exosome-enhanced motility of recipient cells, and clinical survival analysis demonstrated the close correlations between ALDOA or ALDH3A1 expression and poor prognosis of lung cancer patients. After co-culturing with exosomes derived from irradiated cancer cells, the expressions of these metabolic enzymes were elevated and the glycolytic activity was promoted in recipient cancer cells. In conclusion, our data suggested that exosomes from irradiated lung cancer cells regulated the motility of recipient cells by accelerating glycolytic process, where exosomal ALDOA and ALDH3A1 proteins were important signaling factors.

Metastasis suppressor 1 acts as a tumor suppressor by inhibiting epithelial-to-mesenchymal transition in triple-negative breast cancer.

OBJECTIVE: This study aimed to analyze the function of metastasis suppressor 1 (MTSS1) in triple negative breast cancer (TNBC). METHODS: MTSS1 expression in 30 TNBC and paracancerous tissues was measured by quantitative reverse transcriptase polymerase chain reaction. The prognostic value of MTSS1 was assessed by Kaplan-Meier analysis followed by the log-rank test. MCF7 cells were transfected with si-MTSS1, while MDA-MB-231 cells were transfected with pcDNA3.1-MTSS1. Cell proliferation assay and transwell assay were performed to investigate the effects of MTSS1 on the biological behavior of breast cancer cells. Immunofluorescence and western blot were used to detect the influence of MTSS1 on epithelial-mesenchymal transition (EMT) markers. RESULTS: MTSS1 expression was significantly lower in TNBC tissues compared with that in paracancerous tissues (0.012 vs. 0.370; P = 0.006). A lower MTSS1 expression level was also found in tumor tissues of patients with lymph node metastasis (P = 0.002) or tumor node metastasis stage (P = 0.010). Patients with low expression of MTSS1 (⩽ 0.009) had shorter disease-free survival (47.4 vs. 56.0 months; P = 0.012). The knockdown of MTSS1 in MCF7 cells inhibited cell proliferation, enhanced cell migration and invasion capacities, decreased the E-cadherin level, and increased the vimentin level, whereas overexpression of MTSS1 in MDA-MB-231 cells had the opposite effects (P < 0.05). CONCLUSIONS: Our findings demonstrated that MTSS1 regulates proliferation, invasion, migration, and EMT in TNBC, and that decreased MTSS1 is associated with shorter disease-free survival.

Comparative Evaluation of the Cytotoxic and Angiogenic Effects of Minocycline and Clindamycin: An In Vitro Study.

INTRODUCTION: This study aimed to compare the cytocompatibility and angiogenic potential of 2 antibiotics (clindamycin [CLIN] and minocycline [MINO]) at distinct concentrations on dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs). METHODS: DPSCs and HUVECs were exposed to cell culture media modified with CLIN or MINO at concentrations ranging from 30 µg/mL-1000 µg/mL. Cell toxicity and proliferation were investigated using the lactate dehydrogenase and tetrazolium reduction assays, respectively. A capillarylike tube formation in vitro assay was conducted to determine the angiogenic potential associated with each antibiotic. Additionally, selected morphometric angiogenesis parameters were determined using dedicated software (WimTube; Onimagin Technologies SCA, Córdoba, Spain). All statistical analyses were performed using 1-way analysis of variance and the Tukey post hoc test (α= .05). RESULTS: The collected data showed that compared with the control (cell culture media, alpha-minimum essential medium Eagle) increasing the antibiotic concentration significantly decreased cell viability and proliferation of both DPSCs and HUVECs. In terms of angiogenic potential, when tested at 30 µg/mL and 50 µg/mL, CLIN significantly amplified tube formation when compared with MINO with angiogenesis parameters (ie, tube length and tube number) similar to the effect promoted by exogenous vascular endothelial growth factor (50 ng/mL). CONCLUSIONS: CLIN was less cytotoxic when compared with MINO at higher concentrations. Of note, CLIN did not hinder the proangiogenic activity induced by vascular endothelial growth factor to the same extent as MINO, suggesting that the replacement of MINO by CLIN might translate into positive implications in the overall regenerative outcome.

Diabetes mellitus and hyperglycemia control on the risk of colorectal adenomatous polyps: a retrospective cohort study.

BACKGROUND: Colorectal cancer (CRC) develops from colorectal adenomatous polyps. This study is to determine if diabetes mellitus (DM), its treatment, and hemoglobin A1c (HbA1c) level are associated with increased risk of colorectal adenomatous polyps. METHODS: This was a retrospective cohort study that included patients who had at least one colonoscopy and were continuously enrolled in a single managed care organization during a 10-year period (2002-2012). Of these patients (N = 11,933), 1800 were randomly selected for chart review to examine the details of colonoscopy and pathology findings and to confirm the diagnosis of DM. Multivariable logistic regression analyses were performed to assess the associations between DM, its treatment, HbA1c level and adenomatous polyps (our main outcome). RESULTS: Among the total of 11,933 patients with a mean (standard deviation) age of 56 (± 8.8) years, 2306 (19.3%) had DM and 75 (0.6%) had CRC. Among the 1800 under chart review, 445 (24.7%) had DM, 11 (0.6%) had CRC and 537 (29.8%) had adenomatous polyps. In bivariate analysis, patients with DM had 1.45 odds of developing adenomatous polyps compared to those without DM. This effect was attenuated (odds ratio = 1.25, 95% CI: 0.96-1.62, p = 0.09) after adjusting for confounders such as age, gender, race/ethnicity, and body mass index. There was no significant association between type or duration of DM treatment or HbA1c level and adenomatous polyps. CONCLUSIONS: Our study confirmed the known increased risk of adenomatous polyps with advancing age, male gender, Hispanic race/ethnicity and higher body mass index. Although it suggested an association between DM and adenomatous polyps, a statistically significant association was not observed after controlling for other potential confounders. Further studies with a larger sample size are needed to further elucidate this relationship.

Influence of Men's Personality and Social Support on Treatment Decision-Making for Localized Prostate Cancer.

BACKGROUND: Optimal treatment for localized prostate cancer (LPC) is controversial. We assessed the effects of personality, specialists seen, and involvement of spouse, family, or friends on treatment decision/decision-making qualities. METHODS: We surveyed a population-based sample of men ≤ 75 years with newly diagnosed LPC about treatment choice, reasons for the choice, decision-making difficulty, satisfaction, and regret. RESULTS: Of 160 men (71 black, 89 white), with a mean age of 61 (±7.3) years, 59% chose surgery, 31% chose radiation, and 10% chose active surveillance (AS)/watchful waiting (WW). Adjusting for age, race, comorbidity, tumor risk level, and treatment status, men who consulted friends during decision-making were more likely to choose curative treatment (radiation or surgery) than WW/AS (OR = 11.1, p < 0.01; 8.7, p < 0.01). Men who saw a radiation oncologist in addition to a urologist were more likely to choose radiation than surgery (OR = 6.0, p = 0.04). Men who consulted family or friends (OR = 2.6, p < 0.01; 3.7, p < 0.01) experienced greater decision-making difficulty. No personality traits (pessimism, optimism, or faith) were associated with treatment choice/decision-making quality measures. CONCLUSIONS: In addition to specialist seen, consulting friends increased men's likelihood of choosing curative treatment. Consulting family or friends increased decision-making difficulty.

Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry.

Postlesional plasticity has been identified in patients with cerebral gliomas by inducing a large functional reshaping of brain networks. Although numerous non-invasive functional neuroimaging methods have extensively investigated the mechanisms of this functional redistribution in patients with cerebral gliomas, little effort has been made to investigate the structural plasticity of cortical and subcortical structures associated with the glioma volume. In this study, we aimed to investigate whether the contralateral cortical and subcortical structures are able to actively reorganize by themselves in these patients. The compensation mechanism following contralateral cortical and subcortical structural plasticity is considered. We adopted the surface-based morphometry to investigate the difference of cortical and subcortical gray matter (GM) volumes in a cohort of 14 healthy controls and 13 patients with left-hemisphere cerebral gliomas [including 1 patients with World Health Organization (WHO I), 8 WHO II, and 4 WHO III]. The glioma volume ranges from 5.1633 to 208.165 cm2. Compared to healthy controls, we found significantly increased GM volume of the right cuneus and the left thalamus, as well as a trend toward enlargement in the right globus pallidus in patients with cerebral gliomas. Moreover, the GM volumes of these regions were positively correlated with the glioma volumes of the patients. These results provide evidence of cortical and subcortical enlargement, suggesting the usefulness of surface-based morphometry to investigate the structural plasticity. Moreover, the structural plasticity might be acted as the compensation mechanism to better fulfill its functions in patients with cerebral gliomas as the gliomas get larger.

Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition.

PURPOSE: Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. MATERIALS AND METHODS: A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux. In some experiments, the A549 cells were respectively transfected with LC3 small interfering RNA (siRNA), or treated with Earle's Balanced Salt Solution (EBSS). RESULTS: We found that hypoxia enhanced cell radioresistance by increasing the induction of autophagy. And after hypoxia stress, the number of mitochondria was reduced but the cellular ROS level was enhanced. It was significant that autophagy may enhance cell radioresistance by reducing ROS during hypoxic treatment. CONCLUSIONS: We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors.

Patient Knowledge and Qualities of Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: Controversy surrounds treatment for localized prostate cancer (LPC). OBJECTIVES: To assess men's localized prostate cancer (LPC) knowledge and its association with decision-making difficulty, satisfaction and regret. METHODS: Population-based sample of 201 men (104 white, 97 black), ≤ 75 years with newly diagnosed LPC completed a self-administered survey. RESULTS: Mean age was 61(±7.6) years; two-thirds had less than a Bachelor's degree. Mean LPC knowledge was low, 5.87 (±2.53, maximum score 11). More than a third of men who received surgery or radiation did not know about serious long-term treatment side effects. Fewer than half of the men correctly answered comparative side effect and survival benefit questions between surgery and radiation. Knowledge gaps were greatest among black men, men with lower education, single men. Tumor aggressiveness (i.e. PSA level, Gleason score) and treatment choice were not associated with knowledge. Knowledge was not associated with decisional satisfaction or regret. However, greater knowledge was associated with greater decision-making difficulty (P = .018). CONCLUSIONS: Significant LPC knowledge gaps existed across groups, with greater knowledge gaps among black men. The association of decision-making difficulty with knowledge was independent of race. Better patient education is needed, but may not alleviate men's decision-making difficulty due to inherent scientific uncertainty.