tbuckley/cabot-search huggingface dataset:
Recent advances in cell sheet technology for bone and cartilage regeneration: from preparation to application
Authors: Yuezhi Lu, Wenjie Zhang, Jie Wang, Guangzheng Yang, Shi Yin, Tingting Tang, Chunhua Yu, Xinquan Jiang
Journal: International Journal of Oral Science (2019)

Bone defects caused by trauma, tumour resection, infection and congenital deformities, together with articular cartilage defects and cartilage-subchondral bone complex defects caused by trauma and degenerative diseases, remain great challenges for clinicians. Novel strategies utilising cell sheet technology to enhance bone and cartilage regeneration are being developed. The cell sheet technology has shown great clinical potential in regenerative medicine due to its effective preservation of cell-cell connections and extracellular matrix and its scaffold-free nature. This review will first introduce several widely used cell sheet preparation systems, including traditional approaches and recent improvements, as well as their advantages and shortcomings. Recent advances in utilising cell sheet technology to regenerate bone or cartilage defects and bone-cartilage complex defects will be reviewed. The key challenges and future research directions for the application of cell sheet technology in bone and cartilage regeneration will also be discussed.
Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials
Authors: Wenhui Xie, Yanrong Huang, Shiyu Xiao, Xiaoying Sun, Yong Fan, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). Methods PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method. Results 26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03). Conclusion The existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.
CLINICAL OUTCOME OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY ESOPHAGEAL NEOPLASMS IN THE WEST: CAN WE REPRODUCE JAPANESE RESULTS?
Authors: R Gardone, M Salgado Pedrosa, V Arantes
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) is considered more challenging in the esophagus due thin wall and narrow lumen. The aim of this study is to present the clinical outcome of a ten-year experience with esophageal ESD in a Western center.
Esophageal laceration after percutaneous endoscopic gastrostomy tube removal attempt: alternative route of extraction
Authors: João Fernandes, Rui Ramos, Célia Vicente, Tobias Teles, Jorge Canena, Luís Lopes, Carlos Casteleiro
Journal: Endoscopy (2019)

Removal of a percutaneous endoscopic gastrostomy (PEG) tube is recommended after patients resume oral intake [1]. There are three main techniques described to remove a PEG tube: 1) external traction at the skin level; 2) the cut and push technique; and 3) retrograde esophageal exteriorization under endoscopic control [1] [2] [3]. The choice depends mainly on endoscopist preference and local guidelines. Several risk factors for tube deterioration have been described, such as heat and fungal colonization [3] [4].
DNA methylation markers of breast cancer response to anthracycline based neoadjuvant chemotherapy
Authors: V.O. Sigin, V.V. Strelnikov, N.V. Litviakov, O.A. Simonova, I.V. Volodin, E.M. Slonimskaya, A.S. Tanas, D.V. Zaletaev, E.B. Kuznetsova, M.M. Tsyganov
Journal: Annals of Oncology (2019)

Background: Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of locally advanced breast cancer (BC). The aim of this study is to provide a better insight into BC response to neoadjuvant anthracycline based chemotherapy. Methods: Genome-wide methylation analysis of 27 BC biopsy specimens of the luminal B subtype taken before the treatment was performed using the XmaI-RRBS method. Methylation status of the selected markers was next determined by methylation sensitive restriction enzyme PCR in a validating sample of 40 BC biopsy specimens. Results: By XmaI-RRBS we have identified 10 genes the states of methylation of which most effectively mark BC luminal B sensitivity to anthracycline based NAC. For locus specific assessment of these markers we have developed a multi-locus methylation sensitive PCR system. Based on the methylotyping results obtained for the 40 samples of the validating cohort, the diagnostic properties of the system were estimated: the area under the ROC curve was 84%, with the sensitivity of 82% and the specificity of 80%. Conclusions: The system including a limited number of methylation markers makes it possible to effectively predict the response of luminal B subtype BC to anthracycline based NAC by an analysis of biopsy material obtained before the treatment. Reasonable diagnostic sensitivity and specificity values are achieved only when the markers are evaluated in complex; in separate the differences in gene methylation frequencies between responding and non-responding tumors may be negligible (Table). Table80P Methylation frequencies of selected genes in tumors responding and not responding to anthracycline based NACGeneResponders, %Non-responders, %SLC9A328 (7/25)27 (4/15)C1QL220 (5/25)13 (2/15)DPYS60 (15/25)47 (7/15)IRF472 (18/25)33 (5/15)ADCY864 (16/25)40 (6/15)KCNQ248 (12/25)40 (6/15)TERT80 (20/25)60 (9/15)SYNDIG120 (5/25)20 (3/15)SKOR256 (14/25)67 (10/15)GRIK184 (21/25)87 (13/15) Open table in a new tab Legal entity responsible for the study: Research Centre for Medical Genetics. Funding: Russian Science Foundation (project No.18-15-00430). Disclosure: All authors have declared no conflicts of interest.
Understanding the Profile of Cancer-Related Cognitive Impairments: A Critique of Meta-Analyses
Authors: Todd S Horowitz, Melissa Treviño, Ingrid M Gooch, Korrina A Duffy
Journal: JNCI Journal of the National Cancer Institute (2019)

A large body of evidence indicates that cancer survivors who have undergone chemotherapy have cognitive impairments. Substantial disagreement exists regarding which cognitive domains are impaired in this population. We suggest that is in part due to inconsistency in how neuropsychological tests are assigned to cognitive domains. The purpose of this paper is to critically analyze the meta-analytic literature on cancer-related cognitive impairments (CRCI) to quantify this inconsistency. We identified all neuropsychological tests reported in seven meta-analyses of the CRCI literature. Although effect sizes were generally negative (indicating impairment), every domain was declared to be impaired in at least one meta-analysis and unimpaired in at least one other meta-analysis. We plotted summary effect sizes from all the meta-analyses and quantified disagreement by computing the observed and ideal distributions of the one-way χ2 statistic. The actual χ2 distributions were noticeably more peaked and shifted to the left than the ideal distributions, indicating substantial disagreement among the meta-analyses in how neuropsychological tests were categorized to domains. A better understanding of the profile of impairments in CRCI is essential for developing effective remediation methods. To accomplish this goal, the research field needs to promote better agreement on how to measure specific cognitive functions.
Abstract 3448: Overexpression of the steroid inactivating UGT2B28 enzyme is associated with high circulating androgens, tumor aggressiveness and adverse prostate cancer outcome
Authors: Anaïs Belledant, Hélène Hovington, Hervé Brisson, Bernard Têtu, Yves Fradet, Louis Lacombe, Patrick Caron, Chantal Guillemette, Eric Lévesque
Journal: Cancer Research (2015)

Abstract Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by uridine diphospho-glucuronosyltransferase enzymes, namely UGT2B28. This metabolic pathway controls systemic and local androgen bioavailability along with other biotransformation and transport pathways. In this study, we examined the relationship between UGT2B28 protein expression, circulating steroid levels and prostate cancer phenotype. To study distribution of the UGT2B28 protein in prostatic tissues, we used a specific antipeptide antibody displaying no cross-reactivity against highly identical UGT2B family members. Findings revealed that UGT2B28 cytoplasmic staining of secretory cells was distinctive of early stage tumorigenesis (i.e. prostatic intraepithelial neoplasia) and cancer cells with a variable nuclear staining, whereas normal prostate presented only nuclear enzyme expression. Using tissue microarray analysis, we analyzed 239 localized prostate cancer cases that underwent radical prostatectomy. Compared to patients with prostate tumors displaying absent or weak UGT2B28 staining, those with tumors presenting strong UGT2B28 nuclear expression had significantly lower PSA levels at diagnosis (20%; p = 0.043). UGT2B28 expression in the cytoplasm was also correlated with Gleason scores (p≤0.03) and nodal invasion status (p = 0.024). After adjustments for known prognostic markers including PSA, Gleason score, margin and nodal status, tumor size, smoking and germline UGT2B28 deletion status, overexpression of the UGT2B28 protein was an adverse and independent prognostic factor associated with disease recurrence and/or death (HR = 2.82; 95%CI, 1.09-7.36; p = 0.033). Remarkably, prostatic overexpression of UGT2B28 concurs with 30% higher circulating levels of testosterone (p = 0.004) and dihydrotestosterone (p = 0.002), measured by mass spectrometry. Our observations demonstrate that an increased expression of the UGT2B28 enzyme is associated with circulating steroid hormone levels, disease aggressiveness and risk of cancer progression. Citation Format: Anaïs Belledant, Hélène Hovington, Hervé Brisson, Bernard Têtu, Yves Fradet, Louis Lacombe, Patrick Caron, Chantal Guillemette, Eric Lévesque. Overexpression of the steroid inactivating UGT2B28 enzyme is associated with high circulating androgens, tumor aggressiveness and adverse prostate cancer outcome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3448. doi:10.1158/1538-7445.AM2015-3448
Abstract 17174: Comparative Economics of Transcatheter and Surgical Aortic Valve Replacements in Medicare Patients
Authors: Fenton H McCarthy, Katherine M McDermott, Vinay U Kini, Howard C Herrmann, Joseph E Bavaria, Saif Anwaruddin, Jay Giri, Wilson Y Szeto, Peter W Groeneveld, Nimesh D Desai
Journal: Circulation (2015)

Objectives: To describe the economics of transcatheter aortic valve replacement (TAVR) in the US, and to compare costs and payments for TAVR with surgical aortic valve replacement (SAVR) in the context of expanding clinical indications for TAVR. Methods: Hospital charges and Medicare payments from Medicare claims for patients undergoing SAVR or TAVR between January and December 2012. Medicare payments represent actual payments to hospitals accounting for transfer penalties. Cost-to-charge ratios were used to estimate hospital costs from charges. Costs and payments were examined in propensity score matched TAVR and SAVR patients. Results: Medicare spent $215,770,218 nationally for TAVR in 2012, the first year of commercial implantation. Hospital costs were significantly higher for TAVR (median $50,200; interquartile range (IQR) $39,800 - $64,300) than SAVR ($45,500; $34,500 - $63,300; p &lt;0.01) largely due to higher estimated medical supply costs, which includes the implanted valve prosthesis (Table 1, Figure 1). Medicare payments were lower for TAVR ($50,100; $37800 - $65400) than for SAVR hospitalizations ($51,200; $38,300 - $66,700; p&lt;0.01). Median difference between payments and costs was -$3380 for TAVR and $2390 for SAVR hospitalizations (p&lt;0.01). For hospitals to break even on TAVR, overall costs need to decrease by 7% or isolated medical supply costs (primarily related to the TAVR valve) by 22%. Conclusions: Among patients of similar risk, TAVR was associated with higher hospital costs despite shorter ICU and hospital stays compared to SAVR. Overall and/or medical device cost reductions are necessary for TAVR to have a net neutral financial impact on hospitals.
Crystal Structures of the Full-Length Murine and Human Gasdermin D Reveal Mechanisms of Autoinhibition, Lipid Binding, and Oligomerization
Authors: Zhonghua Liu, Chuanping Wang, Jie Yang, Bowen Zhou, Rui Yang, Rajesh Ramachandran, Derek W. Abbott, Tsan Sam Xiao
Journal: Immunity (2019)
Growing a new human kidney
Authors: Adrian S. Woolf
Journal: Kidney International (2019)

There are 3 reasons to generate a new human kidney. The first is to learn more about the biology of the developing and mature organ. The second is to generate tissues with which to model congenital and acquired kidney diseases. In particular, growing human kidneys in this manner ultimately should help us understand the mechanisms of common chronic kidney diseases such as diabetic nephropathy and others featuring fibrosis, as well as nephrotoxicity. The third reason is to provide functional kidney tissues that can be used directly in regenerative medicine therapies. The second and third reasons to grow new human kidneys are especially compelling given the millions of persons worldwide whose lives depend on a functioning kidney transplant or long-term dialysis, as well as those with end-stage renal disease who die prematurely because they are unable to access these treatments. As shown in this review, the aim to create healthy human kidney tissues has been partially realized. Moreover, the technology shows promise in terms of modeling genetic disease. In contrast, barely the first steps have been taken toward modeling nongenetic chronic kidney diseases or using newly grown human kidney tissue for regenerative medicine therapies.
DEVELOPMENT AND FEASIBILITY OF A METHOD TO IMPROVE THE DIAGNOSTIC VALUE OF MAGNETICALLY ASSISTED CAPSULE ENDOSCOPY IN THE DETECTION OF ESOPHAGEAL DISORDERS
Authors: B Dorottya Lovasz, Z Dubravcsik, K Zsobrak, M Szalai, P Schmiedt, L Madacsy
Journal: Endoscopy (2019)

Esophageal disorders, especially reflux esophagitis and Barrett's esophagus are common diseases. The non-invasive visualization of the esophagus is not solved yet. Esophagogastroduodenoscopy (EGD) is the gold standard diagnostic test, however it is uncomfortable for patients without sedation. The aim of the current study was to develop a method with magnetically assisted capsule endoscopy (MACE) for esophageal investigation and to perform a feasibility study of its use in patients.
Simultaneous, quantitative detection of multiple biomarkers in breast cancers using semiconductor multicolor quantum dots
Authors: Ahmad H. Al-Hajj, Max Yezhelyev, Tongrui Liu, Caroline Morris, Xiaohu Gao, Shuming Nie, Ruth M. O’Regan
Journal: Cancer Research (2006)

3587  Background: The management of breast cancer has been significantly advanced by the identification of specific protein profiles, to which specific therapies can be directed. Currently used technologies do not allow for the simultaneous quantification of multiple protein biomarkers on individual breast cancer sections.. We have developed an assay, by conjugating antibodies to semiconductor, multicolor nanoparticles, which allows the quantification of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu on single breast cancer sections, and correlates well with Western blotting and immunohistochemistry (IHC). We have now expanded this assay to allow the detection and quantification of 5 breast cancer-related proteins in single sections of breast cancers and breast cancer cell lines. Methods: We directly conjugated multicolored QDs (525nm, 565nm, 605nm, 655nm, 705nm) to primary antibodies (QD-Abs) for ER, PR, HER2/neu, mTOR (mammalian target of rapamycin) and EGFR (epidermal growth factor receptor) respectively, and stained paraffin embedded sections of breast cancer cell lines (MCF-7, BT474, MDA-231) and human breast tumors. . Results: The use of QD-Abs allowed the detection of all 5 proteins simultaneously on single sections of breast cancer cell lines and breast tumors. Using hyper-spectral imaging and wavelength-resolved spectroscopy, we quantified the expression of each protein, detected using QD-Abs. Our results correlated well with standard methods of detection, including Western blotting. Conclusions: The use of QD-Abs allows the visualization and quantification of 5 clinically important biomarkers simultaneously in single breast cancer sections. The use of multiplex QDs offers the possibility of quantifying many more proteins in single tumor sections, allowing determination of an individual cancer’s proteome. These results raise new possibilities for nano technology applications in molecular pathology and clinical oncology, particularly in linking multiplexed cancer biomarkers with clinical outcome, and allowing the possibility of individualized therapy.
GASTRIC ADENOMA OR EARLY GASTRIC CANCER IS AN IMPORTANT RISK FACTOR FOR COLORECTAL ADENOMA
Authors: JH Lee, J Lee, JI Lee, MW Kim, CG Park, JY Cho
Journal: Endoscopy (2019)

Patients diagnosed gastric cancer have a higher prevalence and increased risk of colorectal cancer. But few studies have investigated the risk of colorectal cancer or adenoma in patients with early gastric cancer or gastric adenoma. The purpose of this study is to investigate the prevalence of colorectal adenoma or cancer in patient with gastric adenoma and early gastric cancer.
Abstract A32: Tumor-matrix tnteractions in early ductal invasions: Integrating histology imaging with computational modeling
Authors: Katarzyna A. Rejniak, Mark C. Lloyd, Agnieszka Kasprzak, Marilyn Bui
Journal: Cancer Research (2017)

Abstract Progression from a ductal carcinoma in situ (DCIS) to an invasive tumor is a major step initiating a devastating and often lethal metastatic cascade. One sentinel event that initiate this process is the development of ductal microinvasions, i.e., small cohorts of tumor cells that breach the basement membrane surrounding the duct, and migrate through the extracellular matrix (ECM). This process is difficult to reproduce experimentally and investigate in a fully controlled way. However, mathematical modeling based on physical principles and medical imaging can shed light on interactions between tumor cells and the surrounding stroma during the spread of microinvasions. We used a combination of advanced image analysis techniques applied to patients' histology data, that include both tissue regions and single cells segmentation, with multi-factorial classification to extract feature data which identifies specific properties of individual tumor cells inside the duct and on the invasive front. These histology-based quantitative data were then used to calibrate a hybrid agent-based mathematical model of DCIS-ECM interactions that takes into account both individual tumor cells and the underlying ECM fibril structure. The model was employed in a computational simulation study to delineate physical properties of the matrix fibers that can facilitate and/or prevent formation and progression of ductal microinvasions. Our integrated approach incorporating medical imaging and computational modeling, allowed us to predict the dynamics of emerging ductal microinvasions that are consistent with the observed clinical data. We showed how changes in the local microenvironmental niche near the DCIS edge leads to initiation of ductal microinvasions. We identified physical properties of the matrix that can facilitate or prevent the progression of such microinvasions. Our methods also provide a tool for quantifying morphological and immunohistochemical properties of individual cells within the mammary ducts and ductal microinvasion, as well as a tool for testing biomechanical hypotheses of tumor cell-tumor matrix interactions. These findings can be directly compared to the patient histology samples and can lead to development of new prognostic methods and therapeutic interventions by targeting the tumor preinvasive niche. Citation Format: Katarzyna A. Rejniak, Mark C. Lloyd, Agnieszka Kasprzak, Marilyn Bui. Tumor-matrix tnteractions in early ductal invasions: Integrating histology imaging with computational modeling. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A32.
Locoregional therapy targeted at the primary tumour improves overall survival in patients with stage IV metastatic breast cancer: A systematic review and meta-analysis with 185942 patients
Authors: R. Gera, K. Mokbel, H. El Hage Chehade, U. Wazir, S. Tayeh
Journal: Annals of Oncology (2019)

Background: Metastatic breast cancer is a complex disease that is traditionally treated using systemic therapy. There is mounting evidence that locoregional therapy (LRT), such as resection of the primary tumour and/or localised radiotherapy could be associated with improvements in survival. We aimed to conduct a meta-analysis to inform decision making. Methods: Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis was undertaken in order to assess whether LRT of the primary tumour in metastatic breast cancer prolongs survival. Results: 43 studies were analysed for the impact of LRT on survival which shown a significant 33.3% reduction in mortality with LRT (HR = 0.667:95% CI 0.617-0.721) and 37.3% with resection alone (N = 41; HR = 0.623: 95% CI 0.586-0.661). Conclusions: This is the largest meta-analysis regarding this question to date. LRT seems to improve overall survival in de novo disease and should be considered in selected patients after a multidisciplinary discussion. Legal entity responsible for the study: London Breast Institute. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells
Authors: Nicholas M. Adams, Clair D. Geary, Endi K. Santosa, Dianne Lumaquin, Jean-Benoît Le Luduec, Rosa Sottile, Kattria van der Ploeg, Joy Hsu, Benjamin M. Whitlock, Benjamin T. Jackson, Orr-El Weizman, Morgan Huse, Katharine C. Hsu, Joseph C. Sun
Journal: Immunity (2019)