104 research outputs found

    Genetically Modified Organisms

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    Determining graphene's induced band gap with magnetic and electric emitters

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    We present numerical and analytical results for the lifetime of emitters in close proximity to graphene sheets. Specifically, we analyze the contributions from different physical channels that participate in the decay processes. Our results demonstrate that measuring the emitters’ decay rates provides an efficient route for sensing graphene’s optoelectronic properties, notably the existence and size of a potential band gap in its electronic band structure

    Significance of tumour regression in lymph node metastases of gastric and gastro-oesophageal junction adenocarcinomas.

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    The presence of lymph node (LN) metastases is one of the most important negative prognostic factors in upper gastrointestinal carcinomas. Tumour regression similar to that in primary tumours can be observed in LN metastases after neoadjuvant therapy. We evaluated the prognostic impact of histological regression in LNs in 480 adenocarcinomas of the stomach and gastro-oesophageal junction after neoadjuvant chemotherapy. Regressive changes in LNs (nodular and/or hyaline fibrosis, sheets of foamy histiocytes or acellular mucin) were assessed by histology. In total, regressive changes were observed in 128 of 480 patients. LNs were categorised according to the absence or presence of both residual tumour and regressive changes (LN-/+ and Reg-/+). 139 cases were LN-/Reg-, 28 cases without viable LN metastases revealed regressive changes (LN-/Reg+), 100 of 313 cases with LN metastases showed regressive changes (LN+/Reg+), and 213 of 313 metastatic LN had no signs of regression (LN+/Reg-). Overall, LN/Reg categorisation correlated with overall survival with the best prognosis for LN-/Reg- and the worst prognosis for LN+/Reg- (p < 0.001). LN-/Reg+ cases had a nearly significant better outcome than LN+/Reg+ (p = 0.054) and the latter had a significantly better prognosis than LN+/Reg- (p = 0.01). The LN/Reg categorisation was also an independent prognostic factor in multivariate analysis (HR = 1.23; 95% CI 1.1-1.38; p < 0.001). We conclude that the presence of regressive changes after neoadjuvant treatment in LNs and LN metastases of gastric and gastro-oesophageal junction cancers is a relevant prognostic factor

    Preoperative Atrial Fibrillation/Flutter Impact on Risk-Adjusted Repeat Aortic Intervention Patients[PROTOCOL]

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    Aim: Impacts of pre-operative atrial fibrillation or flutter (AF/AFL) upon repeat aortic valve replacement (r-AVR) patients’ risk-adjusted short-term outcomes is unknown.Methods: From 2005-2018, New York State AF/AFL versus non-AF/AFL adults’ risk-adjusted r-AVR outcomes were compared. Primary endpoints included the Society of Thoracic Surgeons’ 30-day operative mortality or major morbidity (MM) composite and 30-day readmission (READMIT); the MM sub-components were secondary endpoints. Multivariable logistic regression models evaluated AF/AFL impact upon these endpoints while holding other factors constant.Results: Of 36,783 adults initially undergoing aortic valve replacement, 334 subsequently underwent r-AVR. Within this r-AVR group, 42.4% of repeat surgical (r-SAVR) patients had AF/AFL; 50.4% of repeat transcatheter (viv-TAVR) patients had AF/AFL. R-SAVR AF/AFL patients were older and had more comorbidities than those without AF/AFL. Viv-TAVR AF/AFL patients were similar to those without AF/AFL except for lower rates of chronic obstructive pulmonary disease. Comparing risk-adjusted r-AVR outcomes, AF/AFL did not impact MM [odds ratio (OR), 95% confidence interval (CI): 1.23, 0.66-2.28, P = 0.512] or READMIT (OR, 95%CI: 1.15, 0.60-2.19, P = 0.681). Black race (OR, 95%CI: 2.89, 1.01-8.32, P = 0.049) and Elixhauser mortality score (OR, 95%CI: 1.07, 1.04-1.10, P &lt; 0.0001) predicted MM risk. Cerebrovascular disease (OR, 95%CI: 2.54, 1.23-5.25, P = 0.012) predicted READMIT risk, while viv-TAVR was protective compared to r-SAVR (OR, 95%CI: 0.44, 0.21-0.91, P = 0.027).Conclusion: AF/AFL was not associated with risk-adjusted short-term r-AVR outcomes. Black race, Elixhauser mortality score, and cerebrovascular disease predicted adverse outcomes

    Impact of tumor localization and molecular subtypes on the prognostic and predictive significance of p53 expression in gastric cancer

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    We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein&ndash;Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p &lt; 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact

    Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

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    We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro-oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI-high (MSI-H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI-H and EBV-negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4-63.6) compared with 38.7 months (95% CI 26.3-51.1) for the EMAST-negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2-75.2) and 38.7 months (95% CI 26.2-51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI-H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico-pathological characteristics of gastric carcinoma patients

    Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas

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    BACKGROUND Her2 expression and amplification occurs in a significant subset of gastro-esophageal carcinomas. Her2 is a client protein of molecular chaperones, e.g. heat shock protein (HSP) 90, rendering targeted therapies against Her2/HSP90 an interesting approach. This study aimed to investigate the role and relationship of Her2 and HSP90 in gastric and gastro-esophageal adenocarcinomas. MATERIAL AND METHODS Immunohistochemical determination of HSP90 and Her2 expression was performed on 347 primary resected tumors. Her2 amplification was additionally determined by fluorescence in situ hybridization for all cases. Expression and amplification results were correlated with pathologic parameters (UICC pTNM category, tumor grading) and survival. RESULTS Elevated Her2 copy numbers were observed in 87 tumors, 21 of them showing amplification. 174 tumors showed Her2 immunoreactivity/expression. HSP 90 immunoreactivity was found in 125 tumors. There was no difference between gastric carcinomas and carcinomas of the gastroesophageal junction regarding Her2 or HSP90. Both high HSP90 and Her2 expression/amplification were associated with earlier tumor stages (p<0.01), absence of lymph node metastases (p<0.02) and Laurens intestinal type (p<0.001). HSP90 correlated with Her2 expression and amplification (p<0.001 each). Expressions of HSP90 and Her2, but not Her2 amplification were associated with better prognosis (p=0.02; p=0.004; p=0.802). Moreover, Her2 expression was an independent prognostic factor for overall survival in the subgroup of gastric carcinoma patients (p=0.014) besides pT category, pN category and distant metastases. CONCLUSION Her2 expression and gene amplification occurred in a significant subset of cases. Our results suggest a favorable prognostic impact of Her2 expression. This warrants further investigations regarding the significance of Her2 non-amplified tumors showing Her2 immunoreactivity and the definition of Her2 status in gastric cancers. Moreover, the correlation of Her2 expression with the expression of Her2 chaperoning HSP90 may indicate a synergistic regulation. Targeting HSP90 with or without Her2 may offer additional therapeutic options for gastric carcinoma treatment

    Axon Myelin Transfer of a Non-Enveloped Virus

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    We showed previously that Theiler's virus, a neurotropic non-enveloped picornavirus of mouse, traffics from the axon of infected neurons into the surrounding myelin. When this traffic is interrupted, as in the shiverer mouse which bears a mutation in the myelin basic protein gene, the virus is unable to persist in the central nervous system. In the present work, we used the Wlds mutant mouse, a strain in which axonal degeneration is considerably slowed down, to show that axon to myelin traffic takes place in the absence of axon degeneration. Our results suggest the existence of a mechanism of transfer of axonal cytoplasm into the myelin which Theiler's virus might exploit to ensure its persistence
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