tbuckley/cabot-search huggingface dataset:
Abstract P128: Periodontal Disease and Coronary Artery Calcium in Adults With Type 1 Diabetes
Authors: Janet Snell-bergeon, Amy Alman, Amena Keshawarz, Martin Cech
Journal: Circulation (2020)

Introduction: Adults with type 1 diabetes (T1D) have at least a two-fold risk of developing coronary artery disease (CAD) compared to adults without diabetes (Non-DM); Periodontal disease is also increased in T1D, due at least in part to hyperglycemia. There is increasing recognition that periodontal disease is linked to CAD through systemic inflammation, which may be a mechanism through which diabetes increases CAD. In this study, we examined the association between self-reported gum disease and coronary artery calcium (CAC) in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort. Methods: There were 1416 adults (652 with T1D, 764 Non-DM, mean±SD age 37±8years, 48% men) enrolled in the CACTI cohort in 2000. The cohort completed four visits between 2000 and 2018: at baseline and after 3, 6 and 14 years of follow-up. At each visit, participants self-reported gum disease diagnosis. CAC volume was measured by computed tomography at each visit and was square root transformed for analysis. Linear mixed effects models were used to examine the association between self-reported gum disease and change in CAC volume. Results: At baseline, 12% of Non-DM and 16% of T1D participants (p=0.054) reported having gum disease. The prevalence of gum disease increased across visits to 18% in participants with T1D vs. 13% in Non-DM participants at visit 2 (p=0.01); 22% in participants with T1D at visit 3 vs. 14% in Non-DM participants (p=0.0009) and 25% in participants with T1D vs. 17% in Non-DM participants at visit 4 (p=0.023). Self-reported gum disease was associated with a significantly greater increase in CAC volume over time (Table, p&lt;0.0001) among people with T1D, but not in people without diabetes (p=0.13) when adjusted for age, sex, body mass index, LDL cholesterol and smoking (p-value for diabetes x gum disease interaction &lt;0.0001). Conclusion: Periodontal disease prevalence was increased in adults with T1D, and was independently associated with increase in CAC volume over 14 years of follow-up in this population.
抗癌療法標的としてのDNA修復酵素,チロシルDNAホスホジエステラーゼ(TDP1) | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Y Pommier, T S Dexheimer, C Marchand
Journal: Annals of Oncology (2009)
Metabolically Healthy Obesity
Authors: Matthias Blüher
Journal: Endocrine Reviews (2020)

Abstract Obesity contributes to reduced life expectancy, impaired quality of life, and disabilities, mainly in those individuals who develop cardiovascular diseases, type 2 diabetes, osteoarthritis, and cancer. However, there is a large variation in the individual risk to developing obesity-associated comorbid diseases that cannot simply be explained by the extent of adiposity. Observations that a proportion of individuals with obesity have a significantly lower risk for cardiometabolic abnormalities led to the concept of metabolically healthy obesity (MHO). Although there is no clear definition, normal glucose and lipid metabolism parameters—in addition to the absence of hypertension—usually serve as criteria to diagnose MHO. Biological mechanisms underlying MHO lower amounts of ectopic fat (visceral and liver), and higher leg fat deposition, expandability of subcutaneous adipose tissue, preserved insulin sensitivity, and beta-cell function as well as better cardiorespiratory fitness compared to unhealthy obesity. Whereas the absence of metabolic abnormalities may reduce the risk of type 2 diabetes and cardiovascular diseases in metabolically healthy individuals compared to unhealthy individuals with obesity, it is still higher in comparison with healthy lean individuals. In addition, MHO seems to be a transient phenotype further justifying therapeutic weight loss attempts—even in this subgroup—which might not benefit from reducing body weight to the same extent as patients with unhealthy obesity. Metabolically healthy obesity represents a model to study mechanisms linking obesity to cardiometabolic complications. Metabolically healthy obesity should not be considered a safe condition, which does not require obesity treatment, but may guide decision-making for a personalized and risk-stratified obesity treatment.
Abstract P5-02-13: A novel detection technique for collagen (and other macromolecules) on H&amp;E slides without special stains for improved cancer prognostics
Authors: Farzad Fereidouni, Alexander D. Borowsky, Richard M. Levenson
Journal: Cancer Research (2020)

Abstract Background: Stromal density including the characterization of the type, abundance and alignment of collagen and other extracellular matrix (ECM) protein fibers in proximity to breast precancers and cancers has emerged as an important and evolving tool for understanding tumor progression and stratifying/classifying mortality risk. Standard methods for this evaluation including second harmonic generation (SHG) microscopy requires access to fresh or FFPE tissue samples of limited availability. In contrast, standard diagnostic H&amp;E slides are more readily available for large retrospective and prospective studies. Methods: We developed a method for dual emission and transmission (DUET) microscopy that employs combined brightfield and fluorescence modalities, plus quantitative image analysis. The prototype instrument has whole-slide scanning capabilities for collagen detection and pixel-accurate alignment with conventional H&amp;E-stained images. We have analyzed a retrospective cohort of 700 breast cancers with available outcome follow-up of greater than 5 years using this DUET method Results: DUET microscopy provides clear discrimination of collagen and ECM directly from standard H&amp;E specimens, requiring only a few minutes to scan whole slides. Using the method, contrast enhancement similar to special staining techniques (e.g. trichrome, periodic acid Schiff’s, and picrosirius red stains). Image analysis from DUET directly corresponds to SHG data. DUET imaging discriminates between stroma surrounding invasive cancer and benign epithelium. DUET imaging of 700 breast cancers shows outcome correlation. Ongoing multivariate analysis comparing standard measures (grade, tumor infiltrating lymphocytes, tumor phenotype, etc.) to the DUET stromal score will be reported. Conclusions: DUET provides a straightforward, rapid and inexpensive approach for highlighting collagen distribution patterns on existing histology slides. This method should enable current research using improved quantitative tools, including AI-based, for correlation with patient outcomes, by enabling the use of standard and available H&amp;E slides. Citation Format: Farzad Fereidouni, Alexander D. Borowsky, Richard M. Levenson. A novel detection technique for collagen (and other macromolecules) on H&amp;E slides without special stains for improved cancer prognostics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-13.
<i>Lactobacillus reuteri</i> maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa
Authors: Haiqin Wu, Shuang Xie, Jinfeng Miao, Yuchen Li, Zhihua Wang, Minjuan Wang, Qinghua Yu
Journal: Gut Microbes (2020)

Little is known about the regulatory effect of microbiota on the proliferation and regeneration of ISCs. Here, we found that L. reuteri stimulated the proliferation of intestinal epithelia by increasing the expression of R-spondins and thus activating the Wnt/β-catenin pathway. The proliferation-stimulating effect of Lactobacillus on repair is further enhanced under TNF -induced intestinal mucosal damage, and the number of Lgr5+ cells is maintained. Moreover, compared to the effects of C. rodentium on the induction of intestinal inflammation and crypt hyperplasia in mice, L. reuteri protected the intestinal mucosal barrier integrity by moderately modulating the Wnt/β-catenin signaling pathway to avoid overactivation. L. reuteri had the ability to maintain the number of Lgr5+ cells and stimulate intestinal epithelial proliferation to repair epithelial damage and reduce proinflammatory cytokine secretion in the intestine and the LPS concentration in serum. Moreover, activation of the Wnt/β-catenin pathway also induced differentiation toward Paneth cells and increased antimicrobial peptide expression to inhibit C. rodentium colonization. The protective effect of Lactobacillus against C. rodentium infection disappeared upon application of the Wnt antagonist Wnt-C59 in both mice and intestinal organoids. This study demonstrates that Lactobacillus is effective at maintaining intestinal epithelial regeneration and homeostasis as well as at repairing intestinal damage after pathological injury and is thus a promising alternative therapeutic method for intestinal inflammation.
Detection of Covid-19 in Children in Early January 2020 in Wuhan, China
Authors: Weiyong Liu, Qi Zhang, Junbo Chen, Rong Xiang, Huijuan Song, Sainan Shu, Ling Chen, Lu Liang, Jiaxin Zhou, Lei You, Peng Wu, Bo Zhang, Yanjun Lu, Liming Xia, Lu Huang, Yang Yang, Fang Liu, Malcolm G. Semple, Benjamin J. Cowling, Ke Lan, Ziyong Sun, Hongjie Yu, Yingle Liu
Journal: New England Journal of Medicine (2020)

Children with Covid-19 in Wuhan, China A retrospective analysis of routine surveillance data involving children hospitalized in central Wuhan, China, for acute lower respiratory infection in early ...
Disease stabilization (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) or gefitinib (G)
Authors: P. Pronzato, M. Loprevite, A. Brianti, C. Defferrari, G. Catania, F. Grossi
Journal: Journal of Clinical Oncology (2007)

18115 Background: One retrospective study (Hotta K, Ann Oncol 2005), investigating the prognosis of patients (pts) obtaining SD as best response with G treatment, has demonstrated that both progression-free survival (PFS) and survival (S) were significantly longer than those in pts with progressive disease (PD). The aim of this retrospective study was to compare the PFS and S outcome in pts with advanced NSCLC who achieved SD or partial response (PR) after treatment with E or G. Methods: Pooled data from 62 pts, entered into an open label phase II program of E (n=31) and a compassionate-use program of G (n=31), were retrospectively analyzed. E and G were given orally at 150 and 250 mg per day respectively and were continued until disease progression, development of unacceptable toxicity or patient’s refusal. Results: Pts characteristics: median age 69 years (42–85); females= 21 pts (34%); never/former smokers= 16/38 pts (26/61%); adenocarcinoma/BAC= 35/10 pts (56/16%); PS 0/1= 18/38 pts (29/61%). In 16 pts (26%) E or G were given as first-line therapy; 21 pts (34%) had received =2 prior lines of chemotherapy. Six pts (10%) achieved a PR and 18 pts (29%) obtained SD. TTP and OS in pts obtaining PR and SD were comparable: 7 vs 5.5 and 9.7 vs 9.1 months respectively. In progressing pts median TTP and OS were 1.7 and 3.7 months. Conclusions: Our findings indicate the importance of achieving disease control with both E and G treatment. Pts obtaining SD had a similar PFS and S compared with those having PR. An analysis of the role of mutational status and other biomarkers in predicting clinical outcome is currently underway. No significant financial relationships to disclose.
A controlled prospective randomized trial of adjuvant chemoradiotherapy following radical cystectomy in advanced high risk bladder cancer
Authors: M. S. Zaghloul, H. M. Khaled, M. Lotayef, H. William, M. Nazmy, G. Attia
Journal: Journal of Clinical Oncology (2007)

5082 Background: High risk locally advanced bladder cancer patients experienced low survival rates, high local recurrence and high rate of distant metastasis. Postoperative radiotherapy (PORT) improved local control and survival, yet it did not affect distant metastasis. Methods: A prospective randomized trial was performed at NCI, Cairo, Egypt including 146 patients in 2 arms. Patients who underwent radical cystectomy and pelvic lymphadenectomy had to have one or more of the following: stage P3b or P4a, G3 or involved lymphadenopathy. Arm I (74 patients) received PORT 45 Gy/30 fractions/3 weeks. Arm II (72 patients) received 2 courses of adjuvant chemotherapy (Gemcitabine 1 gm/m 2 D1 and D8 and cisplatin 70 mg/m 2 D2), same PORT regimen followed by another 2 courses of Gemcitabine-cisplatin. Results: Chemotherapy and radiation were tolerated with grade 1/2 toxicities. Delayed toxicity was comparable in both arms. The 45-month DFS was 51 ± 12 % in the whole group. This was affected significantly by performance status (p = 0.0001), pathological stage (p = 0.0099), nodal involvement (p = 0.004) and number of risk factors (p = 0.16). Though there was improvement of 45-month DFS from 28 ± 20% in PORT group to 70 ± 6 % in chemoradiotherapy group, yet it did not reach to the level of statistical significance (p = 0.18). Patients having one risk factor, G3 or no nodal involvement in arm II experienced better DFS than those in arm I (p = 0.17, 0.11 and 0.17 respectively). Distant metastasis-free survival (DMF) rate increased with the addition of chemotherapy from 29±21% to 75±6%. This effect was intensified in patients having one risk factor, grade 3 and negative nodes. Conclusions: Adjuvant chemoradiotherapy using Gemcitabine-cisplatin and PORT was tolerable. There was DFS improvement and higher DMF rates with the addition of chemotherapy to PORT (not statistically significant yet). Patients with one risk factor, G3 or no nodal involvement seemed to benefit more from the added chemotherapy. No significant financial relationships to disclose.
Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition (vol 22, pg 762, 2016)
Authors: Monica Vaccari, Shari N Gordon, Slim Fourati, Luca Schifanella, Namal Pm Liyanage, Mark Cameron, Brandon F Keele, Xiaoying Shen, Georgia D Tomaras, Erik Billings, Mangala Rao, Amy W Chung, Karen G Dowell, Chris Bailey-Kellogg, Eric P Brown, Margaret E Ackerman, Diego A Vargas-Inchaustegui, Stephen Whitney, Melvin N Doster, Nicolo Binello, Poonam Pegu, David C Montefiori, Kathryn Foulds, David S Quinn, Mitzi Donaldson, Frank Liang, Karin Lore, Mario Roederer, Richard A Koup, Adrian McDermott, Zhong-Min Ma, Christopher J Miller, Tran B Phan, Donald N Forthal, Matthew Blackburn, Francesca Caccuri, Massimiliano Bissa, Guido Ferrari, Vaniambadi Kalyanaraman, Maria G Ferrari, DeVon Thompson, Marjorie Robert-Guroff, Silvia Ratto-Kim, Jerome H Kim, Nelson L Michael, Sanjay Phogat, Susan W Barnett, Jim Tartaglia, David Venzon, Donald M Stablein, Galit Alter, Rafick-Pierre Sekaly, Genoveffa Franchini
Journal: Nature Medicine (2016)
Abstract P330: Assessment Of The Prevalence Of Arterial Hypertension Depending On Environmental Living Conditions
Authors: Svetlana Glova, Sergey Shlyk
Journal: Circulation (2020)

Materials and methods: A one-stage population-based epidemiological study of a random sample of 3446 people stratified by age and sex from an unorganized population of Rostov-on-Don was performed. In order to determine the association of hypertension and environmental comfort, all the subjects, depending on the environmental comfort of living, were divided into 2 groups, which were formed on the basis of the "Map of environmental comfort of living in the city of Rostov-on-Don", developed by V.V. Privalenko. The total environmental pollution was determined by the dust load, the content of heavy metals and other toxicants in atmospheric deposition, the degree of soil pollution with heavy metals and oil products, the level of occurrence (flooding) and the scale of groundwater pollution, and the noise level. The 1st group included residents living in regions with low to moderate pollution levels; in the 2nd group - with strong and very strong pollution. The duration of residence of respondents in an area with a certain environmental comfort of living was at least 5 years. Statistical processing of the data was carried out using the program Statistica 6.0. Results: When analyzing the frequency of prevalence of AH depending on the environmental comfort of the area of residence, it was found that in people living in environmentally comfortable areas, AH was detected in 639 people (42.86%). At the same time, among the population of Rostov-on-Don living in ecologically uncomfortable areas, hypertension was registered in 396 people (49.26%), which is significantly higher than the prevalence of hypertension in group I (p = 0.003). Analysis of associations of hypertension in the population of Rostov-on-Don and the environmental comfort of the area of residence revealed that in the group of people who lived in ecologically uncomfortable areas, the prevalence of hypertension was significantly higher than in the group of people with environmentally comfortable living conditions: odds ratio = 1.30 (95% confidence interval 1.09-1.54; p = 0.003). When analyzing the average levels of blood pressure depending on the area of residence, it was found that the level of SBP in people living in areas with environmentally uncomfortable conditions is significantly higher (p &lt;0.001) than in people living in environmentally comfortable areas: for men - 140.91 ± 0.8 mmHg and 136.0 ± 0.4 mm Hg, and in women - 133.42 ± 0.5 mm Hg. and 128.2 ± 0.6 mm Hg, respectively. Findings: The prevalence of hypertension among Rostov-on-Don residents living in environmentally uncomfortable areas is significantly higher (p&lt;0.001) than in environmentally comfortable areas (49.26% and 42.86%, respectively).
Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients
Authors: Qiang‐hua Zhou, Hui Han, Jia‐bin Lu, Ting‐yu Liu, Kang‐bo Huang, Chuang‐zhong Deng, Zai‐shang Li, Jie‐ping Chen, Kai Yao, Zi‐ke Qin, Zhuo‐wei Liu, Yong‐hong Li, Sheng‐jie Guo, Yun‐lin Ye, Fang‐jian Zhou, Ran‐yi Liu
Journal: Cancer Communications (2020)

Abstract Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P &lt; 0.001) but negatively correlated with serum Trp concentration ( P = 0.001). Additionally, IDO1 up‐regulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P &lt; 0.001) and high pathologic grade ( P = 0.008 and 0.032, respectively). High expression level of IDO1 in cancer cells and serum KTR were associated with short disease‐specific survival (both P &lt; 0.001). However, besides N stage (hazard radio [HR], 6.926; 95% confidence interval [CI], 2.458‐19.068; P &lt; 0.001) and pathologic grade (HR, 2.194; 95% CI, 1.021‐4.529; P = 0.038), only serum KTR (HR, 2.780; 95% CI, 1.066‐7.215; P = 0.036) was an independent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon‐γ (IFNγ, P &lt; 0.001) and immunosuppressive markers (programmed cell death protein 1, cytotoxic T‐lymphocyte‐associated protein 4 and programmed death‐ligand 1 and 2; all P &lt; 0.05), and the infiltration of immune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells; all P &lt; 0.001) in PSCC tissues. Furthermore, the expression of IDO1 was induced by IFNγ in a dose‐dependent manner in PSCC cells. Conclusions IFNγ‐induced IDO1 plays a crucial role in immunoediting and immunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1 catabolic activity, can be utilized as an independent prognostic factor for PSCC.
MAPK Pathway Alterations Correlate with Poor Survival and Drive Resistance to Therapy in Patients with Lung Cancers Driven by <i>ROS1</i> Fusions
Authors: Hiroki Sato, Adam J. Schoenfeld, Evan Siau, Yue Christine Lu, Huichun Tai, Ken Suzawa, Daisuke Kubota, Allan J.W. Lui, Besnik Qeriqi, Marissa Mattar, Michael Offin, Masakiyo Sakaguchi, Shinichi Toyooka, Alexander Drilon, Neal X. Rosen, Mark G. Kris, David Solit, Elisa De Stanchina, Monika A. Davare, Gregory J. Riely, Marc Ladanyi, Romel Somwar
Journal: Clinical Cancer Research (2020)

Abstract Purpose: ROS1 tyrosine kinase inhibitors (TKI) provide significant benefit in lung adenocarcinoma patients with ROS1 fusions. However, as observed with all targeted therapies, resistance arises. Detecting mechanisms of acquired resistance (AR) is crucial to finding novel therapies and improve patient outcomes. Experimental Design: ROS1 fusions were expressed in HBEC and NIH-3T3 cells either by cDNA overexpression (CD74/ROS1, SLC34A2/ROS1) or CRISPR-Cas9–mediated genomic engineering (EZR/ROS1). We reviewed targeted large-panel sequencing data (using the MSK-IMPACT assay) patients treated with ROS1 TKIs, and genetic alterations hypothesized to confer AR were modeled in these cell lines. Results: Eight of the 75 patients with a ROS1 fusion had a concurrent MAPK pathway alteration and this correlated with shorter overall survival. In addition, the induction of ROS1 fusions stimulated activation of MEK/ERK signaling with minimal effects on AKT signaling, suggesting the importance of the MAPK pathway in driving ROS1 fusion-positive cancers. Of 8 patients, 2 patients harbored novel in-frame deletions in MEK1 (MEK1delE41_L54) and MEKK1 (MEKK1delH907_C916) that were acquired after ROS1 TKIs, and 2 patients harbored NF1 loss-of-function mutations. Expression of MEK1del or MEKK1del, and knockdown of NF1 in ROS1 fusion-positive cells activated MEK/ERK signaling and conferred resistance to ROS1 TKIs. Combined targeting of ROS1 and MEK inhibited growth of cells expressing both ROS1 fusion and MEK1del. Conclusions: We demonstrate that downstream activation of the MAPK pathway can mediate of innate acquired resistance to ROS1 TKIs and that patients harboring ROS1 fusion and concurrent downstream MAPK pathway alterations have worse survival. Our findings suggest a treatment strategy to target both aberrations.